Surgical Management of Early-Onset Breast Cancer Among Young BRCA1 and BRCA2 Carriers
Abstract
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.
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BibTeX
@article{wong2026surgical,
title = {{Surgical Management of Early-Onset Breast Cancer Among Young BRCA1 and BRCA2 Carriers}},
author = {Stephanie Wong and Eva Blondeaux and Virginia Delucchi and Florence Coussy and Rinat Bernstein Molho and Sabine Linn and Antonio Di Meglio and Ava Kwong and Katarzyna Pogoda and Elisa Agostinetto and Ines Nevelsteen and Judith Balmaña and Halle Moore and Angela Toss and Alberta Ferrari and Christine Rousset-Jablonski and Tiphaine Renaud and Kelly-Anne Phillips and Fedro Peccatori and Maria Agustina Ipina and Shani Paluch-Shimon and Jai Min Ryu and Wanda Cui and Minna Lee and Robert Fruscio and Mariya Rozenblit and Claudio Vernieri and Alexios Matikas and Maria Vittoria Dieci and Fergus Couch and Laura de Marchis and Shelley Hwang and Dione Aguilar y Mendez and Deniz Can Guven and Monique Swain and Caterina Gianni and Stefano Spinaci and Giacomo Montagna and Matteo Lambertini and Hee Jeong Kim},
journal = {JAMA Network Open},
year = {2026},
month = aug,
doi = {10.1001/jamanetworkopen.2026.30856},
url = {https://hal.science/hal-05749317v1},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Surgical Management of Early-Onset Breast Cancer Among Young BRCA1 and BRCA2 Carriers
AU - Stephanie Wong
AU - Eva Blondeaux
AU - Virginia Delucchi
AU - Florence Coussy
AU - Rinat Bernstein Molho
AU - Sabine Linn
AU - Antonio Di Meglio
AU - Ava Kwong
AU - Katarzyna Pogoda
AU - Elisa Agostinetto
AU - Ines Nevelsteen
AU - Judith Balmaña
AU - Halle Moore
AU - Angela Toss
AU - Alberta Ferrari
AU - Christine Rousset-Jablonski
AU - Tiphaine Renaud
AU - Kelly-Anne Phillips
AU - Fedro Peccatori
AU - Maria Agustina Ipina
AU - Shani Paluch-Shimon
AU - Jai Min Ryu
AU - Wanda Cui
AU - Minna Lee
AU - Robert Fruscio
AU - Mariya Rozenblit
AU - Claudio Vernieri
AU - Alexios Matikas
AU - Maria Vittoria Dieci
AU - Fergus Couch
AU - Laura de Marchis
AU - Shelley Hwang
AU - Dione Aguilar y Mendez
AU - Deniz Can Guven
AU - Monique Swain
AU - Caterina Gianni
AU - Stefano Spinaci
AU - Giacomo Montagna
AU - Matteo Lambertini
AU - Hee Jeong Kim
PY - 2026
DA - 2026/08/26
JO - JAMA Network Open
DO - 10.1001/jamanetworkopen.2026.30856
UR - https://hal.science/hal-05749317v1
AB - 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.
SN - 2574-3805
ER -