Surgical Management of Early-Onset Breast Cancer Among Young BRCA1 and BRCA2 Carriers

Vollständiger Abstract

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Importance Young BRCA carriers may undergo breast-conserving surgery (BCS) or mastectomy with or without contralateral risk-reducing mastectomy at the time of an index breast cancer diagnosis. A variety of factors may influence surgical decision-making. Objective To explore surgical patterns of care and factors associated with uptake of bilateral mastectomy among affected BRCA1 or BRCA2 ( BRCA1/2 ) carriers diagnosed with early-onset breast cancer. Design, Setting, and Participants The BRCA BCY Collaboration is an international, hospital-based retrospective cohort study conducted at 109 centers across 5 continents. Women aged 40 years or younger with germline pathogenic or likely pathogenic variants in BRCA1/2 who were diagnosed between January 1, 2000, and December 31, 2020, with invasive stage I to III breast cancer were included. Data were collected between January 2022 and June 2024, and analyses were performed between May 21 and 28, 2025. Main Outcome and Measures The main outcome was the evaluation of surgical management as primary treatment for a first diagnosis of invasive breast cancer, defined as BCS, unilateral mastectomy, or bilateral mastectomy. Results Of 5660 eligible BRCA1/2 carriers, 4715 women (median [IQR] age, 35 [31-38] years) had unilateral stage I to III breast cancer with surgical treatment details available. In the cohort, 1805 patients (38.3%) underwent BCS, 1752 (37.2%) underwent unilateral mastectomy, and 1158 (24.6%) underwent bilateral mastectomy. The proportion of BRCA1/2 carriers undergoing BCS decreased over the study period (55.7% [49 of 88] in 2000 vs 27.0% [82 of 304] in 2020), whereas the use of bilateral mastectomy significantly increased (8.0% [7 of 88] in 2000 vs 44.4% [135 of 304] in 2020). Bilateral mastectomy was more common in women who had genetic testing performed before (248 of 435 [57.0%]) or within 6 months (729 of 1892 [38.5%]) of a breast cancer diagnosis compared with those tested after diagnosis (111 of 2167 [5.1%]). On multivariable analysis, compared with those tested after diagnosis, earlier genetic testing was the factor most strongly associated with bilateral mastectomy receipt (testing prior to diagnosis: adjusted odds ratio, 20.72 [95% CI, 15.27-28.13]; testing at diagnosis: adjusted odds ratio, 6.83 [95% CI, 5.39-8.66]). In subgroup analyses, including 2327 patients who had genetic testing performed before or within 6 months of diagnosis, 977 (42.0%) underwent bilateral mastectomy, with the lowest rates reported in Asia and Africa (130 of 499 [26.1%]) and the highest rates reported in North America (233 of 351 [66.4%]). Conclusions and Relevance The findings of this cohort study of young BRCA1/2 carriers suggest that geographic region and timing of genetic testing were the factors most strongly associated with surgical management.