/ en Fri, 22 Aug 25 10:01:54 -0400 /news/breast-cancer-therapy-can-raise-uterine-cancer-risk-through-unique-mechanism <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" title="Friday, August 22, 2025 - 10:01" class="datetime">August 22, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source 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The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source 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</div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Fri, 22 Aug 2025 14:01:54 +0000 tulrich@broadinstitute.org 5559301 at /news/blood-based-test-provides-new-diagnostic-approach-multiple-myeloma <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" title="Friday, August 22, 2025 - 10:01" class="datetime">August 22, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT" alt="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." title="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Breast cancer cells (blue) in a mouse model. 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Fri, 08 Aug 2025 15:00:00 +0000 tulrich@broadinstitute.org 5559256 at /news/boston-childrens-hospital-dana-farber-cancer-institute-and-broad-clinical-labs-launch <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" title="Friday, August 22, 2025 - 10:01" class="datetime">August 22, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT" alt="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." title="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Breast cancer cells (blue) in a mouse model. 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Thu, 07 Aug 2025 15:19:13 +0000 tulrich@broadinstitute.org 5559306 at /news/technology-brings-new-precision-to-genome-editing <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" title="Friday, August 22, 2025 - 10:01" class="datetime">August 22, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT" alt="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." title="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Breast cancer cells (blue) in a mouse model. </div> </div> </article> 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Wed, 06 Aug 2025 19:06:44 +0000 tulrich@broadinstitute.org 5559251 at /news/breathing-low-oxygen-air-slows-parkinsons-progression-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block 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height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Wed, 06 Aug 2025 13:26:25 +0000 Corie Lok 5558971 at /news/genomics-points-potential-targeted-treatment-options-pediatric-gliomas <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" title="Friday, August 22, 2025 - 10:01" class="datetime">August 22, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT" alt="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." title="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Breast cancer cells (blue) in a mouse model. </div> </div> </article> 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Fri, 01 Aug 2025 18:13:45 +0000 tulrich@broadinstitute.org 5559231 at /news/study-finds-biomarkers-drug-targets-risk-factors-most-common-form-lung-cancer <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" title="Friday, August 22, 2025 - 10:01" class="datetime">August 22, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT" alt="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." title="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Breast cancer cells (blue) in a mouse model. 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Thu, 31 Jul 2025 15:55:57 +0000 Corie Lok 5559226 at /news/collaboration-aims-reduce-animal-use-drug-safety-testing <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" title="Friday, August 22, 2025 - 10:01" class="datetime">August 22, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT" alt="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." title="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Breast cancer cells (blue) in a mouse model. </div> </div> </article> 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Tue, 29 Jul 2025 17:13:59 +0000 leah@broadinstitute.org 5559201 at /news/scientists-apply-optical-pooled-crispr-screening-identify-potential-new-ebola-drug-targets <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block 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height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT" alt="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." title="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Breast cancer cells (blue) in a mouse model. 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Thu, 24 Jul 2025 09:00:00 +0000 leah@broadinstitute.org 5558991 at /news/prime-editing-treats-childhood-brain-disease-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" class="datetime">August 22, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Breast cancer therapy can raise uterine cancer risk through a unique mechanism</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Tamoxifen encourages uterine cell growth in mice without causing mutations; findings could change how some breast cancers are treated in the future</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Mass General Brigham Communications </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-22T10:01:54-04:00" title="Friday, August 22, 2025 - 10:01" class="datetime">August 22, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=DGSwLlXW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=ghcP2Idy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=XAZXgJMd 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=qxK8_baa 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/breast%20cancer%20cells%20from%20mouse%20model%20nci-vol-10573-72.jpg?itok=0ObJ_-QT" alt="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." title="Microscopic view of a breast cancer tumor in a mouse model, with dense clusters of irregular cancer cells stained blue." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: NCI Visuals Online </div> <div class="media-caption__description"> Breast cancer cells (blue) in a mouse model. </div> </div> </article> 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field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=UU_DR2w3 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=0YWGVSxP 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=ecLzoa4Z 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/669e9848082749391a41623b_2048px-Breast_DCIS_Cribriform_PA_crop.png?itok=MhwsLHDF" alt="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." title="A histopathology image of ductal carcinoma in situ (DCIS) of the breast. The image shows a section of breast tissue stained with hematoxylin and eosin, revealing clusters of abnormal cells within the milk ducts. The ducts are filled with atypical cells exhibiting a cribriform pattern, characterized by round to oval spaces within the neoplastic cell clusters. The surrounding tissue appears dense and fibrous." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-cheap-and-effective-biomarkers-dcis-tumor-stage" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify cheap and effective biomarkers for DCIS tumor stage</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=6jcyIAa9 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=Y4NsqzeJ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=l04qk--8 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/26289119085_fce4719cdb_k%20%281%29.jpg?h=f4761ccc&itok=P6xIvL9O" alt="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" title="Microscopy image of human breast cancer tissue showing tumor cells in purple and connective tissue in pink" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-map-communities-single-cells-metastatic-breast-cancers" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers map communities of single cells in metastatic breast cancers</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=EoUmRlgR 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=rYSHmKns 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=bJr64rtR 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2022/TNBC_cells-nci-vol-10502-150.jpeg?itok=XC4Fcy5w" alt="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" title="Triple-negative breast cancer cells (blue). (Credit: <a href="https://visualsonline.cancer.gov/details.cfm?imageid=10502" target="_blank">NCI</a>)" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/proteogenomics-reveals-markers-chemotherapy-resistance-and-outcome-triple-negative-breast" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Proteogenomics reveals markers of chemotherapy resistance and outcome in triple negative breast cancer</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Studies show that people receiving tamoxifen, a highly effective and commonly used therapy to treat breast cancer, face a 2- to 7-fold increased risk of developing uterine cancer within 2-5 years of tamoxifen treatment compared to the general population. While this secondary cancer risk remains relatively low and tamoxifen continues to provide substantial benefit for most patients, it is important to understand even small risks to improve long-term outcomes.</p> <p>In a new study published in <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank"><em>Nature Genetics</em></a>, researchers at Mass General Brigham, the ӳ����ý of MIT and Harvard, Dana Farber Cancer Institute, and Berlin Institute of Health (BIH) at Charité shed light on the mechanism underlying this link and how blocking a specific molecular pathway may offer a way to prevent uterine cancers from occurring in patients taking tamoxifen.<br>  <br> “Our findings suggest that tamoxifen activates a cell growth signaling pathway in cells in the uterus,” said co-corresponding author <a href="/node/4864">Gad Getz</a>, director of bioinformatics at the Mass General Cancer Center, a core institute member in the ӳ����ý's <a href="/node/8529">Cancer Program</a>, and director of the institute's <a href="/node/45711">Cancer Genome Computational Analysis group</a>. <br>  <br> “Importantly, they also point to a potential way to intervene to prevent patients with breast cancer from developing a second, serious cancer in the future,” said co-corresponding author, BIH professor, and ӳ����ý associated scientist Kirsten Kübler, formerly a research fellow in medicine at Mass General Brigham.<br>  <br> The researchers performed whole exome sequencing of 21 uterine cancers that were associated with previous tamoxifen use, and compared their genetic makeup with those of non-tamoxifen-associated uterine cancers in published databases. They found only 14 percent of post-tamoxifen uterine cancers harbored cancer-related <em>PIK3CA</em> mutations, compared to 48 percent of uterine cancers diagnosed in women who hadn’t taken tamoxifen. This finding of lower rates of <em>PIK3CA</em> mutations, a key component of the PI3K pathway, in tamoxifen-exposed patients was validated in three independent cohorts.<br>  <br> To see how tamoxifen might induce cancer without inducing genetic changes, the researchers exposed mice to estrogen, tamoxifen, or no treatment. Compared to the other groups, mice exposed to tamoxifen had greater activity in the P13K-AKT pathway, which regulates uterine cell growth, in part through insulin-like growth factor 1 (IGF1), a hormone that encourages cell growth. <br>  <br> Researchers then exposed mice to both tamoxifen and alpelisib, a drug that blocks the P13K pathway and is also used in the treatment of breast cancer. The addition of alpelisib significantly decreased PI3K-AKT signaling, IGF1 receptor activation, and cell proliferation.<br>  <br> Importantly, the study suggests that blocking the PIK3 pathway could reduce the low but concerning risk of tamoxifen-associated uterine cancer. <br>  <br> “Future clinical research can confirm whether combining non-mutant selective PI3K inhibitors with tamoxifen reduces the risk of uterine cancer and ultimately saves lives,” said co-corresponding author Rinath Jeselsohn, who is an associate professor of medicine at DFCI and an associate member of the ӳ����ý.</p> <p><em>Adapted from <a href="https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/breast-cancer-therapy-tamoxifen" target="_blank">a press release</a> issued by Massachusetts General Hospital, part of the Mass General Brigham healthcare system.</em></p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Kübler K, Nadone A, et al. <a href="https://www.nature.com/articles/s41588-025-02308-w" target="_blank">Tamoxifen induces PI3K activation in uterine cancer</a>. <em>Nature Genetics</em>. Online August 22, 2025. DOI: 10.1038/s41588-025-02308-w.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Support for this study was provided by the National Cancer Institute, the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute, the US Department of Defense's Congressionally Directed Medical Research Programs, and other sources.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer-program" hreflang="en">Cancer Program</a></div> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/gad-getz" hreflang="en">Gad Getz</a></div> </div> </div> </div> </div> </div> Mon, 21 Jul 2025 15:37:05 +0000 Corie Lok 5559001 at