Surgical Management of Early-Onset Breast Cancer Among Young BRCA1 and BRCA2 Carriers.
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Wong Stephanie M, Blondeaux Eva, Delucchi Virginia, Coussy Florence, Molho Rinat Bernstein, Linn Sabine, Di Meglio Antonio, Kwong Ava, Pogoda Katarzyna, Agostinetto Elisa, Nevelsteen Ines, Balmaña Judith, Moore Halle C F, Toss Angela, Ferrari Alberta, Rousset-Jablonski Christine, Renaud Tiphaine, Phillips Kelly-Anne, Peccatori Fedro A, Agustina Ipina Maria, Paluch-Shimon Shani, Ryu Jai Min, Cui Wanda, Lee Minna, Fruscio Robert, Rozenblit Mariya, Vernieri Claudio, Matikas Alexios, Dieci Maria Vittoria, Couch Fergus J, De Marchis Laura, Hwang Shelley E, Aguilar Y Mendez Dione, Can Guven Deniz, Swain Monique, Gianni Caterina, Spinaci Stefano, Montagna Giacomo, Lambertini Matteo, Kim Hee Jeong
Аннотация
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.