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.
Genetic Variation in IGF2 and HTRA1 and Breast Cancer Risk among BRCA1 and BRCA2
Brummel, Sean S. , Ding, Yuan Chun , Steele, Linda, Nathanson, Katherine L. , Pfeiler, Georg , Lynch, Henry T., Weitzel, Jeffrey N. , Narod, Steven A. , Ganz, Patricia A. , Daly, Mary B., Olopade, Olufunmilayo I. , Rubinstein, Wendy S. , Blum, Joanne L. , Gillen, Daniel L. , Neuhausen, Susan L. , Domchek, Susan M. , Rebbeck, Timothy R. , Singer, Christian F. , Garber, Judy E. , Couch, Fergus J. , Godwin, Andrew K. , Isaacs, Claudine , Tomlinson, Gail Elizabeth , Tung, Nadine , Weitzel, Jeffrey N , Olopade, Olufunmilayo I , Nathanson, Katherine L
Cancer Epidemiology, Biomarkers & Prevention | August 8, 2011 | Volume: 20 | Issue: 8 | Pages: 1690-1702
Abstract Background: BRCA1 and BRCA2 mutation carriers have a lifetime breast cancer risk of 40% to 80%, suggesting the presence of risk modifiers. We previously identified significant associations in genetic variants in the insulin-like growth factor (IGF) signaling pathway. Here, we investigate additional IGF signaling genes as risk modifiers for breast cancer development in BRCA carriers. Methods: A cohort of 1,019 BRCA1 and 500 BRCA2 mutation carriers were genotyped for 99 single-nucleotide polymorphisms (SNP) in 13 genes. Proportional hazards regression was used to model time from birth to diagnosis of breast cancer for BRCA1 and BRCA2 carriers separately. For linkage disequilibrium (LD) blocks with multiple SNPs, an additive genetic model was used. For an SNP analysis, no additivity assumptions were made. Results: Significant associations were found between risk of breast cancer and LD blocks in IGF2 for BRCA1 and BRCA2 mutation carriers (global P values of 0.009 for BRCA1 and 0.007 for BRCA2), HTRA1 for BRCA1 carriers (global P value of 0.005), and MMP3 for BRCA2 carriers (global P = 0.0000007 for BRCA2). Conclusions: We identified significant associations of genetic variants involved in IGF signaling. With the known interaction of BRCA1 and IGF signaling and the loss of PTEN in a majority of BRCA1 tumors, this suggests that signaling through AKT may modify breast cancer risk in BRCA1 carriers. Impact: These results suggest potential avenues for future research targeting the IGF signaling pathway in modifying risk in BRCA1and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 20(8); 1690–702. ©2011 AACR.