Safety of assisted reproductive techniques in young women harboring germline pathogenic variants in BRCA1/2 with a pregnancy after prior history of breast cancer.


Journal

ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685

Informations de publication

Date de publication:
12 2021
Historique:
received: 16 09 2021
revised: 06 10 2021
accepted: 07 10 2021
pubmed: 15 11 2021
medline: 25 3 2022
entrez: 14 11 2021
Statut: ppublish

Résumé

Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants. This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy. Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group. This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Sections du résumé

BACKGROUND
Knowledge is growing on the safety of assisted reproductive techniques (ART) in cancer survivors. No data exist, however, for the specific population of breast cancer patients harboring germline BRCA1/2 pathogenic variants.
PATIENTS AND METHODS
This is a multicenter retrospective cohort study across 30 centers worldwide including women diagnosed at ≤40 years with stage I-III breast cancer, between January 2000 and December 2012, harboring known germline BRCA1/2 pathogenic variants. Patients included in this analysis had a post-treatment pregnancy either achieved through use of ART (ART group) or naturally (non-ART group). ART procedures included ovulation induction, ovarian stimulation for in vitro fertilization or intracytoplasmic sperm injection, and embryo transfer under hormonal replacement therapy.
RESULTS
Among the 1424 patients registered in the study, 168 were eligible for inclusion in the present analysis, of whom 22 were in the ART group and 146 in the non-ART group. Survivors in the ART group conceived at an older age compared with those in the non-ART group (median age: 39.7 versus 35.4 years, respectively). Women in the ART group experienced more delivery complications compared with those in the non-ART group (22.1% versus 4.1%, respectively). No other apparent differences in obstetrical outcomes were observed between cohorts. The median follow-up from pregnancy was 3.4 years (range: 0.8-8.6 years) in the ART group and 5.0 years (range: 0.8-17.6 years) in the non-ART group. Two patients (9.1%) in the ART group experienced a disease-free survival event (specifically, a locoregional recurrence) compared with 40 patients (27.4%) in the non-ART group. In the ART group, no patients deceased compared with 10 patients (6.9%) in the non-ART group.
CONCLUSION
This study provides encouraging safety data on the use of ART in breast cancer survivors harboring germline pathogenic variants in BRCA1/2, when natural conception fails or when they opt for ART in order to carry out preimplantation genetic testing.

Identifiants

pubmed: 34775302
pii: S2059-7029(21)00262-3
doi: 10.1016/j.esmoop.2021.100300
pmc: PMC8593447
pii:
doi:

Substances chimiques

BRCA1 Protein 0
BRCA1 protein, human 0

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

100300

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure EdA has acted as a scientific advisory board member and has received honoraria from Roche/Genentech, Novartis, Seattle Genetics, Zodiacs, Libbs, Pierre Fabre, and Lilly; has received travel grants from Roche/GNE and GlaxoSmithKline (GSK)/Novartis; and has received research grants through his institution from Roche/GNE, AstraZeneca, GSK/Novartis, and Servier, outside the submitted work. FAP has acted as consultant for Ipsen, Roche Diagnostic, and Merck outside the submitted work. CRJ has acted as a scientific advisory board member and her institution has received honoraria from Bristol Myers Squibb (BMS), Theramex, and Roche; and her institution has received speaker's fees from Theramex and BMS, outside the submitted work. AS has acted as a consultant for Eli Lilly, Pfizer, Novartis, and Roche; has received speaker's fees from Teva, Roche, Pfizer, and Novartis; has received travel grants from Neopharm, Celgene, and Medison; and has received grant support from Novartis and Roche, outside the submitted work. CVG has acted as a consultant, as a scientific advisory board member, and has received speaker's fees from Roche, Novartis, Pfizer, Lilly, and Merck Sharp & Dohme (MSD); and has received research funding from AstraZeneca, Roche, and Pfizer, outside the submitted work. OCC has acted as a scientific advisory board member for Ascires Sistemas Genómicos; and has received grant support from Roche Diagnostics, Neomedic, and Takeda, outside the submitted work. KP has acted as a scientific advisory board member for AstraZeneca, Eli Lilly, Gilead Sciences, MSD, Novartis, Pierre Fabre, Roche, Teva, and Vifor Pharma; has acted as a consultant for AstraZeneca, Novartis, Pfizer, and Roche; has received speaker's fees from Eli Lilly, Medscape, MSD, Mundi Pharma, Novartis, Pfizer, and Roche; has received travel grants from AstraZeneca, Novartis, Pfizer, PharmaMar, and Roche, outside the submitted work. FP has acted as a scientific advisory board member and has received speaker's fees from Amgen, AstraZeneca, Daichi-Sankyo, Eisai, Eli Lilly, Ipsen, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Seagen, and Takeda; has received travel grants from Celgene, GlaxoSmithKline, and Roche; and has received research funding from AstraZeneca, Eisai, and Roche, outside the submitted work. ARF has received honoraria from Bayer, Daiichi Sankyo, Novartis, and Roche; and has received travel grants from Roche, outside the submitted work. JB has acted as consultant for AstraZeneca and Pfizer outside the submitted work. ID has acted as a scientific advisory board member and received grant from Roche; has received speaker's fees from Novartis; and has received travel grants from Theramex and Ferring, outside the submitted work. ML has acted as a consultant for Roche, Lilly, AstraZeneca, Exact Sciences, and Novartis; and has received honoraria from Sandoz, Roche, Lilly, Pfizer, Novartis, Ipsen, and Takeda, outside the submitted work. The remaining authors have no conflicts of interest to declare.

Auteurs

M Condorelli (M)

Department of Obstetrics and Gynecology, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Fertility Clinic, Brussels, Belgium; Research Laboratory on Human Reproduction, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.

M Bruzzone (M)

Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

M Ceppi (M)

Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

A Ferrari (A)

Department of Surgical Sciences, General Surgery III-Breast Surgery, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Clinical Surgical Sciences, University of Pavia, Pavia, Italy.

A Grinshpun (A)

Breast Oncology Unit Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

A S Hamy (AS)

Department of Medical Oncology, Institut Curie, Paris, France.

E de Azambuja (E)

Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.

E Carrasco (E)

Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.

F A Peccatori (FA)

Gynecologic Oncology Department, European Institute of Oncology IRCCS, Milan, Italy.

A Di Meglio (A)

Molecular Predictors and New Targets in Oncology, INSERM Unit 981, Gustave Roussy, Villejuif, France.

S Paluch-Shimon (S)

Breast Oncology Unit Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University, Jerusalem, Israel.

P D Poorvu (PD)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.

M Venturelli (M)

Department of Oncology and Haematology, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.

C Rousset-Jablonski (C)

Department of Surgery, Centre Léon Bérard and INSERM U1290 RESHAPE, Université Claude Bernard Lyon 1, Lyon, France.

C Senechal (C)

Cancer Genetics Unit, Bergonie Institute, Bordeaux, France.

L Livraghi (L)

Medical Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy; University of Siena, Siena, Italy.

R Ponzone (R)

Gynecological Oncology, Candiolo Cancer Institute, FPO - IRCCS, Candiolo, Turin, Italy.

L De Marchis (L)

Division of Medical Oncology, Department of Radiological, Oncological and Pathological Sciences, "La Sapienza" University of Rome, Rome, Italy.

K Pogoda (K)

Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.

A Sonnenblick (A)

Oncology Division, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv, Israel.

C Villarreal-Garza (C)

Breast Cancer Center, Hospital Zambrano Hellion, Tecnologico de Monterrey, San Pedro Garza Garcia, Mexico.

O Córdoba (O)

Obstetrics and Gynecology Department, Hospital Universitari Son Espases, Palma, Spain.

L Teixeira (L)

Breast Disease Unit, Saint-Louis Hospital, APHP, Université de Paris, INSERM U976, Paris, France.

F Clatot (F)

Department of Medical Oncology, Centre Henri Becquerel, Rouen, France.

K Punie (K)

Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.

R Graffeo (R)

Breast Unit of Southern Switzerland (CSSI), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.

M V Dieci (MV)

Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Medical Oncology 2, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.

J A Pérez-Fidalgo (JA)

Department of Medical Oncology, INCLIVA University Hospital of Valencia, CIBERONC, Valencia, Spain.

F P Duhoux (FP)

Department of Medical Oncology, Breast Clinic, Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium.

F Puglisi (F)

Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy; Department of Medicine, University of Udine, Udine, Italy.

A R Ferreira (AR)

Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal.

E Blondeaux (E)

Breast Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.

T Peretz-Yablonski (T)

Breast Oncology Unit Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

O Caron (O)

Department of Medical Oncology, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France.

C Saule (C)

Department of Genetics, Institut Curie, Paris, France.

L Ameye (L)

Data Centre, Institut Jules Bordet and Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.

J Balmaña (J)

Hereditary Cancer Genetics Group, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.

A H Partridge (AH)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.

H A Azim (HA)

Breast Cancer Center, Hospital Zambrano Hellion, Tecnologico de Monterrey, San Pedro Garza Garcia, Mexico.

I Demeestere (I)

Department of Obstetrics and Gynecology, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Fertility Clinic, Brussels, Belgium; Research Laboratory on Human Reproduction, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.

M Lambertini (M)

Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genova, Italy; Department of Medical Oncology, Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy. Electronic address: matteo.lambertini@unige.it.

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