Risk of Breast and Ovarian Cancer After Prophylactic Mastectomy and Salpingo-Oophorectomy in BRCA1/2 Germline Variant Carriers: A Retrospective Cohort Study From a Single German Center.

[BACKGROUND] As the data on BRCA1/2-associated breast and ovarian cancer prevalence after prophylactic surgery has not been exhaustively investigated yet, we aimed to evaluate the cancer prevalence in a single center cohort of BRCA1 and BRCA2 carriers after conducting prophylactic mastectomy, as well as prophylactic bilateral salpingo-oophorectomy (PBSO) respectively.

[METHODS] We included 875 women that were tested positive for a germline variant in the BRCA1/BRCA2 gene (gPV) between 2002 and 2022 at the Center of Hereditary Breast and Ovarian Cancer of the Technical University Munich Germany. Mean follow up was 7.2 years (range 0-44 years; 95% CI: 6.70 to 7.70). We differentiated breast and/or ovarian cancer diseased (n = 643) and non-diseased BRCA1/2 carriers (n = 232).

[RESULTS] Our analysis confirmed the effectiveness of prophylactic surgeries in genetically predisposed women with a gPV in the BRCA1/2 gene. We observed no breast cancer after prophylactic bilateral mastectomy, 2 contralateral breast cancer diseases after contralateral prophylactic mastectomy and 1 extraovarian serous adenocarcinoma after PBSO. Within the entire study collective, a total of 293 have undergone PBSO, with 6 women having an incidental finding of ovarian cancer and STIC respectively (=2.0%; 1.7% gBRCA1 and 0.3% gBRCA2). Our data suggests that, particularly regarding ipsilateral secondary cancer (ISC), higher oncological safety can be achieved through mastectomy rather than breast-conserving surgery (BCS). In the group of patients who had a second breast cancer and were treated with BCS during their first cancer, 18.3% showed an ISC. Within the patients who were first treated with a mastectomy, only 4.3% showed an ISC.

[CONCLUSIONS] Prophylactic surgeries demonstrate high oncological effectiveness in gPV BRCA1/2 carriers. In particular, mastectomy may provide greater protection against ISC compared with BCS. Further studies will have to be conducted to compare ipsilateral cancer prevalence after breast-sparing surgery and mastectomy.