Pregnancy After Breast Cancer in Young BRCA Carriers
Authors: Lambertini Matteo , Blondeaux Eva , Agostinetto Elisa , Hamy Anne-Sophie , Kim Hee Jeong , Di Meglio Antonio , Bernstein Molho Rinat , Hilbers Florentine , Pogoda Katarzyna , Carrasco Estela , Punie Kevin , Bajpai Jyoti , Ignatiadis Michail , Moore Halle C. F. , Phillips Kelly-Anne , Toss Angela , Rousset-Jablonski Christine , Peccatori Fedro A. , Renaud Tiphaine , Ferrari Alberta , Paluch-Shimon Shani , Fruscio Robert , Cui Wanda , Wong Stephanie M. , Vernieri Claudio , Ruddy Kathryn J. , Dieci Maria Vittoria , Matikas Alexios , Rozenblit Mariya , Villarreal-Garza Cynthia , De Marchis Laura , Del Mastro Lucia , Puglisi Fabio , Del Pilar Estevez-Diz Maria , Rodriguez-Wallberg Kenny A. , Mrinakova Bela , Meister Sarah , Livraghi Luca , Clatot Florian , Yerushalmi Rinat , De Angelis Carmine , Sánchez-Bayona Rodrigo , Meattini Icro , Cichowska-Cwalińska Natalia , Berlière Martine , Salama Mahmoud , De Giorgi Ugo , Sonnenblick Amir , Chiodi Camila , Lee Young-Jin , Maria Camille , Azim Hatem A. , Boni Luca , Partridge Ann H. ,   BRCA BCY Collaboration, de Azambuja Evandro , Molinelli Chiara , Paesmans Marianne , Ameye Lieveke , Amant Frédéric , Brems Hilde , Han Sileny , Hatse Sigrid , Nevelsteen Ines , Neven Patrick , Smeets Ann , Van Rompuy Chantal , Wildiers Hans , Duhoux Francois , Giugliano Federica , Criscitiello Carmen , Borea Roberto , Arecco Luca , Chirco Alessandra , Bini Federica , Venturelli Marta , Cortesi Laura , Ponzone Riccardo , Tomasi Cont Nicoletta , Balmaña Judith , Graffeo Rossella , Luna Pais Helena , Mohar Alejandro , Palacios Tamara , Da Ros Lucia , Miolo Gianmaria , Garutti Mattia , Pastò Brenno , Spazzapan Simon , Viel Alessandra , Pérez-Fidalgo Alejandro , Colombo Bonadio Renata , Peretz-Yablonski Tamar , Anghelone Chiara Annunziata Pasqualina , Della Valle Angelica , Campanella Maria , Guarneri Valentina , Bas Raphaelle , Heudel Pierre-Etienne , Tredan Olivier , de Talouet Solenne , Bonadona Valérie , Lasset Christine , Acheritogaray Marion , Senechal Claire , Mariño Monica , Córdoba Octavi , Feldman Didi , Pesce Romina I. , Allemand Carol , Riggi Cecilia , Iriarte Maria Belen , Cortés Salgado Alfonso , Cortes Javier , Gion María , Saavedra Cristina , Rodriguez Adela , Adamo Barbara , Prat Aleix , Hester Anna , Dunckelmann Sofia , Harbeck Nadia , Marhold Maximilian , Bartsch Rupert , Mannsbarth Constantin , Popovic Lazar , Božović-Spasojević Ivana , Krivokuca Ana , Dimitrijevic Marija , Visani Luca , Bettazzi Beatrice , Livi Lorenzo , Sposetti Caterina , Sini Valentina , Rognone Alessia , Bianchini Giampaolo , Patricelli Maria Grazia , Rabaiotti Emanuela , Gentilini Oreste , Fontana Andrea , Acconci Giulia , Baldacci Erica , Bianchini Giulia , Pistelli Mirco , Linn Sabine , Kleiterp Sieta , Moha Daoud A. , Sarin Rajiv , Sekar Anberson , Atzori Francesco , Loi Francesco , Dessì Mariele , O’Connor Sarah , Nesci Stephanie , James Paul , Michael Chris , Couch Fergus J. , Olson Janet E. , Larson Nicole L. , Yadav Siddhartha , Lopetegui Nerea , Carey Lisa A. , Abdou Yara , Zagami Paola , Di Rocco Roberta , Baldassarri Margherita , Bengala Carmelo , Mariamidze Elene , Graff Stephanie L. , Haddad Stephanie A. , Safran Emma , Vasconcelos de Matos Leonor , Ferreira Arlindo , Negri Serena , Dell'Oro Cristina , Inzoli Alessandra , Costa Clarissa , Marchetta Liliana , Lustberg Maryam , Blansky Deanna , Jeon June , Ansari Norin , Aguilar-y-Mendez Dione , Woodruff Teresa K. , Swain Monique , Miller Madison , Leach Richard , Fabi Alessandra , Palazzo Antonella , Paris Ida , Kufel-Grabowska Joanna , Synowiec Agnieszka , Hancinova Miriam , Tarbaj Lukas , Sokolović Emir , Bešlija Semir , Cerić Timur , Hasanbegović Berisa , Foulkes William D , Bianchi Manuel A. , Tolosa Pablo , Alvaro Laura , Eriksson Bergman Louise , Antone Nicoleta , Damian Cristina 
Published: December 2023

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