Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.
Tiphaine Renaud, Antonio Di Meglio, Luca Boni, Matteo Lambertini, Florentine Hilbers, Jyoti Bajpai, Alberta Ferrari, Eva Blondeaux, Anne-Sophie Hamy, Rinat Bernstein Molho, Estela Carrasco, Michail Ignatiadis, Halle C F Moore, Fedro A Peccatori, Kathryn J Ruddy, Shani Paluch-Shimon, Wanda Cui, Stephanie M Wong, Maria Vittoria Dieci, Mariya Rozenblit, Maria Del Pilar Estevez-Diz, Sarah Meister, Natalia Cichowska-Cwalinska, Mahmoud Salama, Camila Chiodi, Young-Jin Lee, Camille Maria, Kelly-Anne Phillips, Katarzyna Pogoda, Elisa Agostinetto, Angela Toss, Alexios Matikas, Luca Livraghi, Christine Rousset-Jablonski, Kenny A Rodriguez-Wallberg, Robert Fruscio, Amir Sonnenblick, Hatem A Azim, Hee Jeong Kim, Martine Berlière, Laura De Marchis, Bela Mrinakova, Lucia Del Mastro, Carmine De Angelis, Rodrigo Sánchez-Bayona, Florian Clatot, Rinat Yerushalmi, Claudio Vernieri, Cynthia Villarreal-Garza, Ugo De Giorgi, Icro Meattini, Ann H Partridge, Kevin Punie, Fabio Puglisi
Journal: JAMA
2024;331(1):49-59
PMID: 38059899
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.
Address:
Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy.; Department of Medical Oncology, U. O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.; U. O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Breast Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium.; Department of Medical Oncology, Universite Paris Cité, Institut Curie, Paris, France.; Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.; Cancer Survivorship Program-Molecular Predicitors and New Targets in Oncology, INSERM Unit 981, Gustave Roussy, Villejuif, France.; Susanne Levy Gertner Oncogenetics Unit, Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center Affiliated to Tel Aviv University, Tel Hashomer, Israel.; Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.; Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.; Hereditary Cancer Genetics Unit, Medical Oncology Department, Vall d´Hebron University Hospital, Vall d´Hebron Institute of Oncology, Barcelona, Spain.; Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.; Department of Medical Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India.; Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.; Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.; Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.; Department of Surgery, Leon Berard Cancer Center, Lyon, France.; Gynecologic Oncology Department, European Institute of Oncology (IRCCS), Milan, Italy.; Cancer Genetics Unit, Bergonie Institute, Bordeaux, France.; Hereditary Breast and Ovarian Cancer Unit and General Surgery 3-Senology, Surgical Department, Fondazione IRCCS Policlinico San Matteo, and University of Pavia, Pavia, Italy.; Breast Oncology Unit, Sharett Institute of Oncology, Hadassah University Hospital, and Faculty of Medicine, Hebrew University, Jerusalem, Israel.; UO Gynecology, Department of Medicine and Surgery, University of Milan-Bicocca, IRCCS San Gerardo dei Tintori, Monza, Italy.; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.; Stroll Cancer Prevention Centre, Jewish General Hospital, and McGill University Medical School, Montreal, Quebec, Canada.; Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.; IFOM ETS, AIRC Institute of Molecular Oncology, Milan, Italy.; Department of Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota.; Dipartimento di Scienze Chirurgiche, Oncologiche, e Gastroenterologiche, Università di Padova, Padova, Italy.; Oncologia 2, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy.; Department of Oncology/Pathology, Karolinska Institute, and Breast Center, Karolinska University Hospital, Stockholm, Sweden.; Department of Medical Oncology, Smilow Cancer Hospital at Yale New Haven, New Haven, Connecticut.; Breast Cancer Center, Hospital Zambrano Hellion-TecSalud, Tecnologico de Monterrey, Monterrey, Mexico.; Department of Radiological, Oncological, and Pathological Sciences, Sapienza University of Rome, Rome, Italy.; Division of Oncology, Department of Hematology, Oncology, and Dermatology, Umberto 1 University Hospital, Rome, Italy.; Department of Medical Oncology, Centro di Riferimento Oncologico di Avano (CRO) IRCCS, Aviano, Italy.; Department of Medicine, University of Udine, Udine, Italy.; Department of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.; Department of Oncology-Pathology, Laboratory of Translational Fertility Preservation, Karolinska Institute, Stockholm, Sweden.; Department of Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden.; First Department of Oncology, Comenius University and St Elisabeth Cancer Institute, Bratislava, Slovakia.; Department of Obstetrics and Gynecology, Ludwig Maximilian University (LMU) Hospital, LMU Munich, Germany.; Department of Medical Oncology, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.; Department of Medical Oncology, Hospital of Prato, Azienda USL Toscana Centro, Italy.; Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.; Department of Medical Oncology, Davidoff Center, Rabin Medical Center, Petah Tikva, Tel Aviv University, Tel Aviv, Israel.; Department of Medical Oncology, University of Naples Federico II, Napoli, Italy.; Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.; Department of Experimental and Clinical Biomedical Sciences M. Serio, University of Florence, and Radiation Oncology Unit, Oncology Department, Florence University Hospital, Florence, Italy.; Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.; Early Phase Clinical Trials Centre, Medical University of Gdańsk, Gdańsk, Poland.; Department of Medical Oncology and Breast Surgery, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCL), Brussels, Belgium.; Oncofertility Consortium and Department of Obstetrics, Gynecology, and Reproductive Biology, Michigan State University, East Lansing.; Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy.; Oncology Division, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.; Breast Cancer Center, Hospital Zambrano Hellion-TecSalud, Tecnologico de Monterrey, Monterrey, Mexico.; Cairo Oncology Center, Cairo, Egypt.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
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MeSH Terms:
Adult,
Female,
Humans,
Pregnancy,
Breast Neoplasms,
Disease-Free Survival,
Germ-Line Mutation,
Retrospective Studies,
Genes, BRCA2,
Genes, BRCA1,
Pregnancy Outcome,
Pregnancy Complications, Neoplastic,
Internationality
