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Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.
Lambertini, Matteo MD 1,2; Blondeaux, Eva MD 3; Agostinetto, Elisa MD 4; Hamy, Anne-Sophie MD 5; Kim, Hee Jeong MD 6; Di Meglio, Antonio MD 7; Bernstein Molho, Rinat MD 8; Hilbers, Florentine PhD 9; Pogoda, Katarzyna MD 10; Carrasco, Estela MD 11; Punie, Kevin MD 12; Bajpai, Jyoti MD 13; Ignatiadis, Michail MD 4; Moore, Halle C. F. MD 14; Phillips, Kelly-Anne MD 15,16,17; Toss, Angela MD 18,19; Rousset-Jablonski, Christine MD 20; Peccatori, Fedro A. MD 21; Renaud, Tiphaine MD 22; Ferrari, Alberta MD 23; Paluch-Shimon, Shani MD 24; Fruscio, Robert MD 25; Cui, Wanda MD 15,16; Wong, Stephanie M. MD 26; Vernieri, Claudio MD 27,28; Ruddy, Kathryn J. MD 29; Dieci, Maria Vittoria MD 30,31; Matikas, Alexios MD 32; Rozenblit, Mariya MD 33; Villarreal-Garza, Cynthia MD 34; De Marchis, Laura MD 35,36; Del Mastro, Lucia MD 1,2; Puglisi, Fabio MD 37,38; Del Pilar Estevez-Diz, Maria MD 39; Rodriguez-Wallberg, Kenny A. MD 40,41; Mrinakova, Bela MD 42; Meister, Sarah MD 43; Livraghi, Luca MD 44,45; Clatot, Florian MD 46; Yerushalmi, Rinat MD 47; De Angelis, Carmine MD 48; Sanchez-Bayona, Rodrigo MD 49; Meattini, Icro MD 50; Cichowska-Cwalinska, Natalia MD 51,52; Berliere, Martine MD 53; Salama, Mahmoud MD 54; De Giorgi, Ugo MD 55; Sonnenblick, Amir MD 56; Chiodi, Camila MD 7; Lee, Young-Jin MD 6; Maria, Camille MD 5; Azim, Hatem A. Jr MD 34,57; Boni, Luca MD 3; Partridge, Ann H. MD 58
[Article] JAMA.

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Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers.

Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers.

Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023.

Exposure: Pregnancy after breast cancer.

Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes.

Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (>=37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival.

Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival.

Trial Registration: ClinicalTrials.gov Identifier: NCT03673306