Clinical Behavior of Breast Cancer in Young <i>BRCA</i> Carriers and Prediagnostic Awareness of Germline <i>BRCA</i> Status
Abstract
PURPOSE To investigate the clinical behavior of breast cancer in young BRCA carriers according to the specific BRCA gene ( BRCA1 v BRCA2 ) and the association of the timing of genetic testing (before v at diagnosis) with prognosis. METHODS This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in BRCA1 or BRCA2 , who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306 ). RESULTS Compared with BRCA2 carriers (n = 1,683), BRCA1 carriers (n = 3,069) had more frequently hormone receptor–negative (74.4% v 15.5%) and high-grade (77.5% v 49.1%) tumors. Similar outcomes were observed in BRCA1 and BRCA2 carriers but with a different pattern and risk of disease-free survival events over time. Compared with patients tested for BRCA at diagnosis (ie, between 2 months before and up to 6 months after diagnosis; n = 1,671), those tested before diagnosis (ie, any time up to 2 months before diagnosis; n = 411) had smaller tumors (T1: 61.3% v 32.4%), less nodal involvement (N0: 65.9% v 50.8%), less frequently received chemotherapy (84.4% v 92.9%), and axillary dissection (37.5% v 47.4%). Patients tested before diagnosis had better overall survival (OS; unadjusted hazard ratio [HR], 0.61 [95% CI, 0.40 to 0.92]); however, this result lost statistical significance after adjustment for potential confounders including tumor stage (adjusted HR, 0.74 [95% CI, 0.47 to 1.15]). CONCLUSION This global study provides evidence on the different clinical behavior of breast cancer in young BRCA1 and BRCA2 carriers. Identifying a BRCA PV in healthy individuals was associated with earlier-stage breast cancer diagnosis and lower treatment burden, as well as better unadjusted OS.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (39)
Matteo Lambertini
Eva Blondeaux
U.O. Epidemiologia Clinica, IRCCS Azienda Ospedaliera Metropolitana, Genova, Italy
Loredana M. Tomasello
Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genoa, Italy
Elisa Agostinetto
Anne-Sophie Hamy
Institut Curie, Université Paris Cité, Paris, France
Hee Jeong Kim
Maria Alice Franzoi
Cancer Survivorship Program, INSERM Unit 981, Gustave Roussy, Villejuif, France
Rinat Bernstein-Molho
Sheba Medical Center, Giv'atayim, Israel
Florentine Hilbers
Department of Molecular Pathology, Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands
Katarzyna Pogoda
Hans Wildiers
Jyoti Bajpai
Department of Medical Oncology, Tata Memorial Centre, Mumbai, India
Michail Ignatiadis
Halle C.F. Moore
Breast Oncology Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
Ann H. Partridge
Dana–Farber Cancer Institute, Harvard Medical School, Boston
Kelly-Anne Phillips
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Angela Toss
Christine Rousset-Jablonski
Department of Surgery, Leon Berard Cancer Centre, Centre Léon Bérard, Lyon, France
Carmen Criscitiello
IRCCS Humanitas Research Hospital, Rozzano, Italy
Tiphaine Renaud
Institut Bergonié, centre régional de lutte contre le cancer, service pharmacie, Bordeaux, France
Alberta Ferrari
Hereditary Breast and Ovarian Cancer (HBOC) Unit and General Surgery 3 - Senology, Breast Cancer Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Shani Paluch-Shimon
Robert Fruscio
Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
Wanda Cui
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
Stephanie M. Wong
Stroll Cancer Prevention Centre, Jewish General Hospital, and McGill University Medical School, Montreal, Canada
Claudio Vernieri
Kathryn J. Ruddy
Maria Vittoria Dieci
Alexios Matikas
Mariya Rozenblit
Yale Cancer Center, Yale School of Medicine, New Haven, CT
Cynthia Villarreal-Garza
Breast Cancer Center, Hospital Zambrano Hellion TecSalud, Tecnologico de Monterrey, Monterrey, NL, Mexico
Laura De Marchis
Sapienza University of Rome, Medical Oncology Department, Policlinico Umberto I, Roma, Italy
Fabio Puglisi
Kenny A. Rodriguez-Wallberg
Karolinska Institutet, Department of Oncology-Pathology, Laboratory of Translational Fertility Preservation, New Karolinska Hospital, ME Gynecology and Reproduction, Stockholm, Sweden
Francois P. Duhoux
Department of Medical Oncology, Institut Roi Albert II, Cliniques universitaires Saint-Luc and Institut de Recherche Expérimentale et Clinique (pôle MIRO)
Luca Livraghi
Nuovo Ospedale di Prato, Prato, Italy
Marco Bruzzone
U.O. Epidemiologia Clinica, IRCCS Azienda Ospedaliera Metropolitana, Genova, Italy
Luca Boni
Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Azienda Ospedaliera Metropolitana, Genova, Italy
Judith Balmana
Hereditary Cancer Genetics, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain