Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2024 Jan 2;331(1):49-59.
doi: 10.1001/jama.2023.25463.

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

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

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

Matteo Lambertini et al. JAMA. .

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Lambertini reported having an advisory role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences; receiving speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Knight, Ipsen, and AstraZeneca; receiving travel grants from Gilead and Daiichi Sankyo; receiving research funding (to his institution) from Gilead; and having nonfinancial interests as the chair of the European Society for Medical Oncology (ESMO) Young Oncologists Committee (YOC) and as a member of the national council of the Italian Association of Medical Oncology. Dr Blondeaux reported receiving research funding (to her institution) from Gilead. Dr Agostinetto reported receiving speaker honoraria from Eli Lilly, Sandoz, AstraZeneca; research funding (to her institution) from Gilead; and meeting/travel grants from Novartis, Roche, Eli Lilly, Genetic, Istituto Gentili, Daiichi Sankyo, AstraZeneca. Dr Pogoda reported receiving honoraria for consultations/lectures/training/clinical trials and payment of conferences fees from AstraZeneca, Gilead, Roche, Novartis, Eli Lilly, Pfizer, MSD, Teva, Egis, and Vipharm. Dr Punie reported receiving research grants (to his institution) from MSD and Sanofi; speaker fees and honoraria for consultancy and advisory board functions from AstraZeneca, Eli Lilly, Exact Sciences, Focus Patient, Gilead, Menarini, MSD, Novartis, Pfizer, Roche, and Seagen; speaker fees and honoraria for consultancy and advisory board functions (to his institution) from AstraZeneca, Eli Lilly, Exact Sciences, Gilead, MSD, Novartis, Pfizer, Roche, and Seagen; stock options from Need Inc; and travel grants from AstraZeneca, Novartis, Pfizer, PharmaMar, and Roche. Dr Bajpai reported receiving research grants (to his institution) from Eli Lilly, Novartis, Roche, AstraZeneca, Paxman Coolers, Samsung Bioepis, and Sun Pharma; conducting nonremunerated advisory board activities for Novartis; and having leadership roles with the Immuno-Oncology Society of India, the Indian Society of Medical and Paediatric Oncology, the Teenage and Young Cancer Association, ESMO, and the Society for Immunotherapy of Cancer. Dr Ignatiadis reported receiving honoraria from Novartis and Seattle Genetics; research grants (to his institution) from Pfizer, Roche, Inivata Inc, Natera Inc, and Gilead; and meeting/travel grants from Roche, AstraZeneca, and Gilead. Dr Moore reported receiving consulting fees from Myovant and research support (to her institution) from Daiichi Sankyo, AstraZeneca, Roche/Genentech, Sermonix, and Seattle Genetics. Dr Phillips reported having an unpaid advisory role for AstraZeneca and receiving research funding (to her institution) from AstraZeneca. Dr Toss reported having an advisory role for Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, and MSD; receiving speaker honoraria from Lilly, Novartis, and Pfizer; and receiving travel grants from Gilead and Daiichi Sankyo. Dr Rousset-Jablonski reported having an advisory role for Bristol Myers Squibb, Roche, and Theramex; receiving speaker honoraria (to her institution) from Novartis, Organon, and Theramex; and receiving research funding (to her institution) from Bayer Healthcare. Dr Cui reported receiving honoraria from Pfizer, Merck, Eisai, and AstraZeneca. Dr Vernieri reported having an advisory role for Novartis, Eli Lilly, Daiichi Sankyo, and Pfizer; consultancy for Eli Lilly; receiving research grants (to his institution) from Roche; and receiving honoraria as a speaker from Novartis, Eli Lilly, Istituto Gentili, and Accedemia di Medicina. Dr Matikas reported consultancy for Veracyte (no compensation); receiving speaker honoraria from Roche and Seagen (to his institution); and receiving research funding (to his institution) from AstraZeneca, Novartis, and MSD. Dr Del Mastro reported receiving grants from Eli Lilly, Novartis, Roche, Daiichi Sankyo, Seagen, AstraZeneca, Gilead, and Pierre Fabre; receiving consulting fees from Eli Lilly, Gilead, and Daiichi Sankyo; receiving speaker honoraria from Roche, Novartis, Pfizer, Eli Lilly, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen, GSK, and Agendia-Stemline; receiving travel grants from Roche, Pfizer, Eisai, Daiichi Sankyo, and AstraZeneca; and having an advisory role for Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sakyo, Exact Sciences, Gilead, Pierre Fabre, Eisai, AstraZeneca, Agendia, GSK, and Seagen. Dr Puglisi reported having an advisory role for and receiving speaker honoraria, travel grants, and research grants from Amgen, AstraZeneca, Daichii Sankyo, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, and Viatris. Dr Rodriguez-Wallberg reported receiving research grants from Novo Nordisk, Merck, and Ferring Pharmaceuticals (to her institution); receiving consulting fees from the Swedish Ministry of Health and Welfare as an expert in assisted reproduction and fertility preservation; and receiving speaker honoraria from Ferring Pharmaceuticals, Roche, Pfizer, Organon, and Merck. Dr Clatot reported having received speaker honoraria from BMS, Merck Serono, MSD, AstraZeneca, Novartis, Gilead, and Daiichi Sankyo and travel grants from Pfizer, Merck Serono, Nutricia, and Novartis. Dr Yerushalmi reported consulting for Roche, Pfizer, Novartis, Rhenium, Eli Lilly, Gilead, and Stemline; receiving research grants from Roche; and receiving speaker honoraria from Roche, Novartis, Medison, MSD, Astra-Zeneca, Eli Lilly, and Stemline. Dr De Angelis reported having an advisory role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo, Gilead, and GSK; receiving speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, GSK, Gilead, and Daiichi Sankyo; receiving travel grants from Gilead; and receiving research support (to her institution) from Novartis, Gilead, and Daiichi Sankyo. Dr Sánchez-Bayona reported receiving travel grants from Pfizer, Gilead, AstraZeneca, and Novartis; receiving honoraria for speaker or advisory board participation from Novartis, Lilly, AstraZeneca, Daiichi Sankyo, Gilead, Roche, GlaxoSmithKline, Clovis Oncology, Seagen, and Accord; and having nonfinancial interests as a member of the ESMO YOC and scientific secretary of the Spanish Society of Medical Oncology. Dr Meattini reported having an advisory role for Eli Lilly, Novartis, Pfizer, Seagen, Gilead, Accuray, AstraZeneca, and Daiichi Sankyo. Dr Azim reported being an employee of Emergence Therapeutics. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Participant Flow
Figure 2.
Figure 2.. Cumulative Incidence of Pregnancy Overall and According to Hormone Receptor Status
Median observation time in the overall cohort was 5.6 years (IQR, 2.9-9.4 years); in patients with hormone receptor–positive disease, 5.8 years (IQR, 3.0-9.3 years); and in patients with hormone receptor–negative disease, 5.6 years (IQR, 2.7-9.6 years).
See this image and copyright information in PMC

Comment in

References

    1. Ruddy KJ, Gelber SI, Tamimi RM, et al. . Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol. 2014;32(11):1151-1156. doi:10.1200/JCO.2013.52.8877 - DOI - PMC - PubMed
    1. Mangiardi-Veltin M, Sebbag C, Rousset-Jablonski C, et al. ; Seintinelles Research Network . Pregnancy, fertility concerns and fertility preservation procedures in a national study of French breast cancer survivors. Reprod Biomed Online. 2022;44(6):1031-1044. doi:10.1016/j.rbmo.2021.12.019 - DOI - PubMed
    1. Copson ER, Maishman TC, Tapper WJ, et al. . Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol. 2018;19(2):169-180. doi:10.1016/S1470-2045(17)30891-4 - DOI - PMC - PubMed
    1. Fine E, Knoll MA, Maslow BL. Fertility considerations for reproductive-aged carriers of deleterious BRCA mutations: a call for early intervention. JCO Oncol Pract. 2022;18(3):165-168. doi:10.1200/OP.21.00389 - DOI - PubMed
    1. Turan V, Lambertini M, Lee DY, et al. . Association of germline BRCA pathogenic variants with diminished ovarian reserve: a meta-analysis of individual patient-level data. J Clin Oncol. 2021;39(18):2016-2024. doi:10.1200/JCO.20.02880 - DOI - PMC - PubMed

Publication types

Associated data