Pregnancy After Breast Cancer in Young <i>BRCA </i>Carriers
Authors: 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 Ferrari, Shani 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, Evandro de Azambuja, Chiara Molinelli, Marianne Paesmans, Lieveke Ameye, Frédéric Amant, Hilde Brems, Sileny Han, Sigrid Hatse, Ines Nevelsteen, Patrick Neven, Ann Smeets, Chantal Van Rompuy, Hans Wildiers, Francois Duhoux, Federica Giugliano, Carmen Criscitiello, Roberto Borea, Luca Arecco, Alessandra Chirco, Federica Bini, Marta Venturelli, Laura Cortesi, Riccardo Ponzone, Nicoletta Tomasi Cont, Judith Balmaña, Rossella Graffeo, Helena Luna Pais, Alejandro Mohar, Tamara Palacios, Lucia Da Ros, Gianmaria Miolo, Mattia Garutti, Brenno Pastò, Simon Spazzapan, Alessandra Viel, Alejandro Pérez-Fidalgo, Renata Colombo Bonadio, Tamar Peretz-Yablonski, Chiara Annunziata Pasqualina Anghelone, Angelica Della Valle, Maria Campanella, Valentina Guarneri, Raphaelle Bas, Pierre-Etienne Heudel, Olivier Tredan, Solenne de Talouet, Valérie Bonadona, Christine Lasset, Marion Acheritogaray, Claire Senechal, Monica Mariño, Octavi Córdoba, Didi Feldman, Romina I. Pesce, Carol Allemand, Cecilia Riggi, Maria Belen Iriarte, Alfonso Cortés Salgado, Javier Cortes, María Gion, Cristina Saavedra, Adela Rodriguez, Barbara Adamo, Aleix Prat, Anna Hester, Sofia Dunckelmann, Nadia Harbeck, Maximilian Marhold, Rupert Bartsch, Constantin Mannsbarth, Lazar Popovic, Ivana Božović-Spasojević, Ana Krivokuca, Marija Dimitrijevic, Luca Visani, Beatrice Bettazzi, Lorenzo Livi, Caterina Sposetti, Valentina Sini, Alessia Rognone, Giampaolo Bianchini, Maria Grazia Patricelli, Emanuela Rabaiotti, Oreste Gentilini, Andrea Fontana, Giulia Acconci, Erica Baldacci, Giulia Bianchini, Mirco Pistelli, Sabine Linn, Sieta Kleiterp, Daoud A. Moha, Rajiv Sarin, Anberson Sekar, Francesco Atzori, Francesco Loi, Mariele Dessì, Sarah O’Connor, Stephanie Nesci, Paul James, Chris Michael, Fergus J. Couch, Janet E. Olson, Nicole L. Larson, Siddhartha Yadav, Nerea Lopetegui, Lisa A. Carey, Yara Abdou, Paola Zagami, Roberta Di Rocco, Margherita Baldassarri, Carmelo Bengala, Elene Mariamidze, Stephanie L. Graff, Stephanie A. Haddad, Emma Safran, Leonor Vasconcelos de Matos, Arlindo Ferreira, Serena Negri, Cristina Dell'Oro, Alessandra Inzoli, Clarissa Costa, Liliana Marchetta, Maryam Lustberg, Deanna Blansky, June Jeon, Norin Ansari, Dione Aguilar-y-Mendez, Teresa K. Woodruff, Monique Swain, Madison Miller, Richard Leach, Alessandra Fabi, Antonella Palazzo, Ida Paris, Joanna Kufel-Grabowska, Agnieszka Synowiec, Miriam Hancinova, Lukas Tarbaj, Emir Sokolović, Semir Bešlija, Timur Cerić, Berisa Hasanbegović, William D Foulkes, Manuel A. Bianchi, Pablo Tolosa, Laura Alvaro, Louise Eriksson Bergman, Nicoleta Antone, Cristina Damian
Journal: JAMA (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