npj Breast Cancer (Feb 2021)
Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants
- Matteo Lambertini,
- Marcello Ceppi,
- Anne-Sophie Hamy,
- Olivier Caron,
- Philip D. Poorvu,
- Estela Carrasco,
- Albert Grinshpun,
- Kevin Punie,
- Christine Rousset-Jablonski,
- Alberta Ferrari,
- Shani Paluch-Shimon,
- Angela Toss,
- Claire Senechal,
- Fabio Puglisi,
- Katarzyna Pogoda,
- Jose Alejandro Pérez-Fidalgo,
- Laura De Marchis,
- Riccardo Ponzone,
- Luca Livraghi,
- Maria Del Pilar Estevez-Diz,
- Cynthia Villarreal-Garza,
- Maria Vittoria Dieci,
- Florian Clatot,
- Francois P. Duhoux,
- Rossella Graffeo,
- Luis Teixeira,
- Octavi Córdoba,
- Amir Sonnenblick,
- Arlindo R. Ferreira,
- Ann H. Partridge,
- Antonio Di Meglio,
- Claire Saule,
- Fedro A. Peccatori,
- Marco Bruzzone,
- Marie Daphne t’Kint de Roodenbeke,
- Lieveke Ameye,
- Judith Balmaña,
- Lucia Del Mastro,
- Hatem A. Azim
Affiliations
- Matteo Lambertini
- Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova
- Marcello Ceppi
- Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino
- Anne-Sophie Hamy
- Department of Medical Oncology, Institut Curie
- Olivier Caron
- Department of Medical Oncology, Institut Gustave Roussy, Université Paris-Saclay
- Philip D. Poorvu
- Department of Medical Oncology, Dana-Farber Cancer Institute
- Estela Carrasco
- Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron Barcelona Hospital Campus
- Albert Grinshpun
- Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center
- Kevin Punie
- Department of General Medical Oncology and Multidisciplinary Breast Centre, Leuven Cancer Institute, University Hospitals Leuven
- Christine Rousset-Jablonski
- Department of Surgery, Centre Léon Bérard
- Alberta Ferrari
- Department of Surgical Sciences, General Surgery III - Breast Surgery, Fondazione IRCCS Policlinico San Matteo, University of Pavia, aBRCAdaBRA onlus
- Shani Paluch-Shimon
- Breast Oncology Unit, Shaare Zedek Medical Centre and Department of Oncology, Sheba Medical Center, Tel Hashomer
- Angela Toss
- Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico di Modena
- Claire Senechal
- Cancer Genetics Unit, Bergonie Institute
- Fabio Puglisi
- Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS
- Katarzyna Pogoda
- Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology
- Jose Alejandro Pérez-Fidalgo
- Department of Medical Oncology, INCLIVA University Hospital of Valencia, CIBERONC
- Laura De Marchis
- Division of Medical Oncology, Department of Radiological, Oncological and Pathological Sciences, “La Sapienza” University of Rome
- Riccardo Ponzone
- Gynecological Oncology, Candiolo Cancer Institute, FPO – IRCCS, Candiolo
- Luca Livraghi
- Medical Oncology Unit, ASST Papa Giovanni XXIII
- Maria Del Pilar Estevez-Diz
- Departament of Oncology, Instituto do Cancer do Estado de Sao Paulo – Faculdade de Medicina da Universidade de Sao Paulo
- Cynthia Villarreal-Garza
- Department of Research and Breast Tumors, Mexican National Cancer Institute
- Maria Vittoria Dieci
- Department of Surgery, Oncology and Gastroenterology, University of Padua
- Florian Clatot
- Department of Medical Oncology, Centre Henri Becquerel
- Francois P. Duhoux
- Department of Medical Oncology, Breast Clinic, Cliniques Universitaires Saint-Luc, UCLouvain
- Rossella Graffeo
- Breast Unit of Southern Switzerland (CSSI), Oncology Institute of Southern Switzerland
- Luis Teixeira
- Breast Disease Unit, Saint-Louis Hospital, APHP, Université de Paris, INSERM U976
- Octavi Córdoba
- Obstetrics and Gynecology Department, Hospital Universitari Son Espases
- Amir Sonnenblick
- Oncology Division, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine
- Arlindo R. Ferreira
- Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation
- Ann H. Partridge
- Department of Medical Oncology, Dana-Farber Cancer Institute
- Antonio Di Meglio
- Predictive Biomarkers and New Therapeutic Strategies in Oncology, INSERM Unit 981, Gustave Roussy
- Claire Saule
- Department of Genetics, Institut Curie
- Fedro A. Peccatori
- Gynecologic Oncology Department, European Institute of Oncology IRCCS
- Marco Bruzzone
- Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino
- Marie Daphne t’Kint de Roodenbeke
- Department of Medicine, Institut Jules Bordet and Université Libre de Bruxelles (U.L.B.)
- Lieveke Ameye
- Data Centre, Institut Jules Bordet and Université Libre de Bruxelles (U.L.B.)
- Judith Balmaña
- Hereditary Cancer Genetics Group, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron Barcelona Hospital Campus
- Lucia Del Mastro
- Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova
- Hatem A. Azim
- Breast Cancer Center, Hospital Zambrano Hellion, Tecnologico de Monterrey
- DOI
- https://doi.org/10.1038/s41523-021-00224-w
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 9
Abstract
Abstract Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60–0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94–2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients’ counseling on treatment, prevention, and surveillance strategies.
