Pregnancy after Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study

Matteo Lambertini, Eva Blondeaux, Elisa Agostinetto, Anne Sophie Hamy, Hee Jeong Kim, Antonio Di Meglio, Rinat Bernstein Molho, Florentine Hilbers, Katarzyna Pogoda, Estela Carrasco, Kevin Punie, Jyoti Bajpai, Michail Ignatiadis, Halle C.F. Moore, Kelly Anne Phillips, Angela Toss, Christine Rousset-Jablonski, Fedro A. Peccatori, Tiphaine Renaud, Alberta FerrariShani Paluch-Shimon, Robert Fruscio, Wanda Cui, Stephanie M. Wong, Claudio Vernieri, Kathryn J. Ruddy, Maria Vittoria Dieci, Alexios Matikas, Mariya Rozenblit, Cynthia Villarreal-Garza, Laura De Marchis, Lucia Del Mastro, Fabio Puglisi, Maria Del Pilar Estevez-Diz, Kenny A. Rodriguez-Wallberg, Bela Mrinakova, Sarah Meister, Luca Livraghi, Florian Clatot, Rinat Yerushalmi, Carmine De Angelis, Rodrigo Sánchez-Bayona, Icro Meattini, Natalia Cichowska-Cwalińska, Martine Berlière, Mahmoud Salama, Ugo De Giorgi, Amir Sonnenblick, Camila Chiodi, Young Jin Lee, Camille Maria, Hatem A. Azim, Luca Boni, Ann H. Partridge

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)49-59
Number of pages11
JournalJAMA
Volume331
Issue number1
DOIs
StatePublished - Jan 2 2024

ASJC Scopus subject areas

  • General Medicine

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