Citations 2
The Risk of Breast Cancer According to Mutation Type and Position in Carriers of a Pathogenic Variant in BRCA1
Apostol, Adriana Ionelia , Metcalfe, Kelly , Jorgji, Dimitri , Cybulski, Cezary , Gronwald, Jacek , Lubiński, Jan , Møller, Pål , Kim, Raymond H. , Aeilts, Amber M. , Cajal, Teresa Ramón y , Pal, Tuya , Bordeleau, Louise , Karlan, Beth Y. , Couch, Fergus J., Zakalik, Dana , Fruscio, Robert , Tung, Nadine, Sun, Ping, Monteiro, Álvaro N.A. , Narod, Steven A. , Akbari, Mohammad R. , Apostol, Adriana I , Jorgji, Dimitri , Cybulski, Cezary , Gronwald, Jacek , Lubinski, Jan , Kim, Raymond H , Aeilts, Amber M , Ramón Y Cajal, Teresa , Pal, Tuya , Karlan, Beth Y , Fruscio, Robert , Monteiro, Alvaro N , Narod, Steven A , Metcalfe, Kelly A , Bordeleau, Louise , Kotsopoulos, Joanne , Singer, Christian F. , Foulkes, William D. , Sun, Ping
Current Oncology | December 15, 2025 | Volume: 32 | Issue: 12 | Pages: 705
Background: Carriers of a pathogenic variant (PV) in BRCA1 face a high risk of breast cancer. This study estimated the risk of developing breast cancer according to mutation type and location. Methods: BRCA1 carriers with no personal history of breast cancer or bilateral mastectomy were included. Detailed information on clinical and family history was collected by questionnaire. Survival analysis was used to estimate 15-year cumulative risk according to PV type and location. Results: A total of 3677 BRCA1 carriers were followed for a mean of 7.2 years (range 0.1–15.0 years); 481 incident breast cancers were documented. Overall, the 15-year cumulative incidence was 25%. Risk estimates varied by exon, ranging from 9% (exon 21) to 19% (exon 12) to 36% (exon 15); however, strata were small. Carriers of four founder mutations common in Eastern Europe (c.5263_5264insC, c.181T > G, c.66_67delAG and c.4034delA) experienced a lower-than-expected cancer risk (15.9–24.4%) compared to other PVs (28.8%) (p = 0.02). Conclusions: Although our data suggests some variability in penetrance based on specific BRCA1 PV, this was based on a large number of founder mutations. Breast cancer management strategies should continue to be based on comprehensive risk assessment.
Endometriosis in Carriers of a Pathogenic Variant in BRCA1 or BRCA2: A Descriptive Analysis of a Large Multicentral BRCA Carrier Cohort
Mokhber, Aghaghia , Stewart, Bethany , Gronwald, Jacek , Cybulski, Cezary , Kim, Raymond H. , Karlan, Beth Y. , Bordeleau, Louise , Cajal, Teresa Ramón y , Pal, Tuya , Eisen, Andrea , Couch, Fergus J., Zakalik, Dana , Tung, Nadine, Fruscio, Robert , Sun, Ping, Lubiński, Jan , Narod, Steven A. , Stewart, Brynne , Gronwald, Jacek , Cybulski, Cezary , Kim, Raymond H , Karlan, Beth Y , Ramón Y Cajal, Teresa , Pal, Tuya , Eisen, Andrea , Fruscio, Robert , Lubinski, Jan , Narod, Steven A , Bordeleau, Louise , Terry, Kathryn L. , Couch, Fergus J. , Tung, Nadine , Foulkes, William D. , Aeilts, Amber M. , Sun, Ping , Kotsopoulos, Joanne
Current Oncology | December 5, 2025 | Volume: 32 | Issue: 12 | Pages: 675
Background: Endometriosis affects an estimated 10% of reproductive-aged women and is associated with increased ovarian cancer risk. While BRCA1/2 mutations are established risk factors for ovarian cancer, their association with endometriosis remains unclear. This study aimed to characterize the prevalence and clinical features of endometriosis within a large cohort of BRCA mutation carriers. Methods: A descriptive analysis was conducted using data from a multi-center longitudinal cohort of women with pathogenic BRCA variants. Reproductive history and related factors were collected through self-reported questionnaires and compared. Results: Among 16,950 BRCA carriers, the prevalence of endometriosis was 2.4%. Compared to BRCA carriers without endometriosis, those with endometriosis were more likely to carry a BRCA2 mutation, have post-secondary education, and experience earlier menarche. BRCA carriers with endometriosis had a lower ovarian cancer prevalence than those without (10% vs. 15%, p < 0.001). Conclusions: This is the first study of this scale to report the prevalence of endometriosis among BRCA mutation carriers, which was lower than previously reported in the general population. The association between endometriosis and ovarian cancer does not appear to be generalizable to this population. Further prospective studies are warranted to clarify this association among BRCA mutation carriers.