Citations 2
Risk of Breast Cancer After Ovarian Cancer in Women With a Pathogenic/Likely Pathogenic Variant in BRCA1 or BRCA2
Apostol, Adriana Ionelia , Gronwald, J., Cybulski, C., Kim, Raymond H. , Møller, P., Karlan, B., Bordeleau, Louise , Schrader, Intan , Cajal, Teresa Ramón y , Pal, Tuya, Eisen, Andrea, Singer, Christian F., Couch, Fergus J., Zakalik, Dana , Metcalfe, Kelly , Olopade, Olufunmilayo, Tung, Nadine, Fruscio, R, Foulkes, William D., Sun, P., Lubinski, J., Narod, Steven A., Sweet, Kevin , Elser, Christine , Panchal, Seema, Wiesner, Georgia L. , Armel, Susan, Steele, Linda, Serfas, Kim, Cullinane, Carey A., Reilly, Robert E., Mercer, L J, Dungan, Jeffrey R., Cohen, Stephanie, Neuhausen, Susan, Sun, Sophie, Blum, Joanne L., Stempa, Klaudia , Graham, Tracy Ann, Seca, Marta , Marchette, Martina Delle , Dell'Oro, Cristina, Alfonso, Rosa Moreno, Lopez, Consol, Cusco, Francesco, Karlan, Beth Y. , Schrader, Kasmintan A. , Eisen, Andrea , Apostol, Adriana I , Cybulski, Cezary , Karlan, Beth Y , Ramón Y Cajal, Teresa , Singer, Christian F , Couch, Fergus J. , Olopade, Olufunmilayo I , Tung, Nadine , Fruscio, Robert , Foulkes, William D , Aeilts, Amber M , Lubinski, Jan , Narod, Steven A , Kotsopoulos, Joanne , Metcalfe, Kelly A , Eisen, Andrea , Bordeleau, Louise , Kim, Raymond H , Cybulski, Cezary , Møller, Pål , Pal, Tuya , Singer, Christian F. , Couch, Fergus J. , Olopade, Olufunmilayo I. , Tung, Nadine , Foulkes, William D. , Aeilts, Amber M. , Lubiński, Jan , Narod, Steven A. , Kotsopoulos, Joanne , Steele, Linda, Saal, Howard M. , Rayson, Daniel , Mercer, Leanne, Cohen, Stephanie, Neuhausen, Susan L, Senter, Leigha , Blum, Joanne Lorraine , Negri, Serena , Dell’Oro, Cristina, Inzoli, Alessandra , Alfonso, Rosa
Journal of Clinical Oncology | February 28, 2026 | Volume: 44 | Issue: 10 | Pages: 883-892
PURPOSE BRCA carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ovarian ). Among BRCA carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer BRCA carriers after a diagnosis of ovarian cancer. METHODS We included women with a pathogenic/likely pathogenic variant in BRCA1 or BRCA2 , a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer. RESULTS A total of 960 participants with ovarian cancer were identified (814 BRCA1 and 146 BRCA2 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer–related deaths occurred. Among 741 age-matched BRCA carriers without ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; P < .0001). CONCLUSION After ovarian cancer, BRCA carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.
Abstract GS3-01: Menopausal Hormone Therapy and the Risk of Breast Cancer in Women with a Pathogenic Variant in BRCA1 or BRCA2
Kotsopoulos, J., Seca, M., Jacek, G., Huzarski, T., Møller, P., Kim, R. H., Singer, C. F., Karlan, B., Cajal, T. Ramon y, Pal, Tuya, Bordeleau, Louise , Foulkes, W., Tung, N. M., Couch, F. J., Neuhausen, S., Zakalik, Dana , Cybulski, C., Olopade, O. I., Metcalfe, K., Fruscio, R, Sun, P., Lubinski, J., Narod, S., Eisen, Andrea , Metcalfe, Kelly , Kim, Raymond H. , Metcalfe, Kelly A , Eisen, Andrea , Bordeleau, Louise , Kim, Raymond H , Kotsopoulos, Joanne , Seca, Marta , Huzarski, T., Møller, Pål , Kim, R.H., Singer, Christian F. , Karlan, Beth Y. , Aeilts, Amber M. , Pal, Tuya , Eisen, Andrew , Foulkes, William D. , Couch, F.J., Neuhausen, Susan L. , Cybulski, Cezary , Lubiński, Jan
Clinical Cancer Research | February 17, 2026 | Volume: 32 | Issue: 4_Supplement | Pages: GS3-01-GS3-01
10.1158/1557-3265.sabcs25-gs3-01
Abstract Background: Women with a pathogenic variant in the BRCA1 or BRCA2 gene (carriers) are at a high risk of developing ovarian cancer and recommended to undergo bilateral salpingo-oophorectomy at an early age resulting in surgical menopause. Menopausal hormone therapy (MHT) is the most effective way to mitigate the adverse outcomes of early menopause; however, the safety of MHT on breast cancer risk in this population has not been established. Methods: We conducted a prospective matched analysis of MHT use following menopause (predominantly surgical) and breast cancer risk in BRCA carriers using a matched prospective analysis to emulate a randomized clinical trial. Women without a history of any cancer or bilateral mastectomy and who were enrolled in a longitudinal study with detailed data collection were eligible for inclusion. Women who initiated MHT (exposed) after menopause were matched one-to-one to women who had not initiated MHT (unexposed) by gene, year of birth, and age at menopause, resulting in 676 matched pairs. Cox proportional hazards regression to estimate the hazard ratios (HR) and 95%CIs (CI) of incident breast cancer associated with MHT use. Results: After a mean follow-up of 5.6 years from the date of first MHT use in the exposed woman, there were 87 incident breast cancer cases in the exposed group (12·9%) and 128 cases in the unexposed group (18·9%) (P = 0·002). Compared to their unexposed match, women who used estrogen (E) experienced a significant decrease in the risk of breast cancer (HR = 0·37; 95%: CI 0·24-0·57). There was no protective (or adverse) effect associated with the use of E plus progestogen (E+P) (HR = 0·94; 95%CI 0·54-1·63), with progestogen alone (P) (HR = 1·14; 95%CI: 0·21-6·22) or with tibolone (HR = 0·57; 95%CI: 0·19-1·69). There were no diagnoses of breast cancer in the 43 women who used a CEE + bazedoxifene. Findings were similar for carriers of either gene mutation. Conclusion: To our knowledge, this represents the largest prospective report of MHT use and breast cancer risk in BRCA1 and BRCA2 carriers. Our findings showed no increase in the risk of breast cancer with the use of MHT, irrespective of gene mutation or formulation. These findings provide an evidence-based approach for the management of women at high-risk of breast cancer who are facing the acute and chronic effects of early surgical menopause. The safe use of MHT by BRCA carriers will continue to be an important research topic as formulations continue to evolve. Citation Format: J. Kotsopoulos, M. Seca, G. Jacek, T. Huzarski, P. Møller, R. H. Kim, C. Singer, B. Karlan, A. Aeilts, T. Ramon y Cajal, T. Pal, A. Eisen, L. Bordeleau, W. Foulkes, N. Tung, F. Couch, S. Neuhausen, D. Zakalik, C. Cybulski, O. Olopade, K. Metcalfe, R. Fruscio, P. Sun, J. Lubinski, S. Narod, Hereditary Breast Cancer Clinical Study Group. Menopausal Hormone Therapy and the Risk of Breast Cancer in Women with a Pathogenic Variant in BRCA1 or BRCA2 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS3-01.