Sistema de Salut de Catalunya
Institut Català de la Salut
[Lambertini M] Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genoa, Italy. Medical Oncology Department, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. [Blondeaux E] U. O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. [Tomasello LM] Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genova, Genoa, Italy. Section of Medical Oncology, Department of Precision Medicine in Medical, Surgical and Clinical Care (Me.Pre.C.C), University of Palermo, Palermo, Italy. [Agostinetto E] Medical Oncology Department, Institut Jules Bordet, Université Libre de Bruxelles (U.L.B.), Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium. [Hamy AS] Department of Medical Oncology, Université Paris Cite, Institut Curie, Paris, France. [Kim HJ] Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. [Balmaña J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Hereditary Cancer Genetics Unit, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-07-04T10:34:27Z
2025-07-04T10:34:27Z
2025-05-10
Càncer de mama; Línia germinal BRCA
Cáncer de mama; Línea germinal BRCA
Breast cancer; Germline BRCA
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
Published version
English
Mama - Càncer - Aspectes genètics; Mama - Càncer - Diagnòstic; Mama - Càncer - Propensió; Anomalies cromosòmiques; DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms; Other subheadings::Other subheadings::/diagnosis; PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation::Germ-Line Mutation; DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Susceptibility::Genetic Predisposition to Disease; CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Fanconi Anemia Complementation Group Proteins::BRCA1 Protein; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama; Otros calificadores::Otros calificadores::/diagnóstico; FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación::mutación de la línea germinal; ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::susceptibilidad a enfermedades::predisposición genética a la enfermedad; COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas de grupos de complementación de la anemia de Fanconi::proteína BRCA1
American Society of Clinical Oncology
Journal of Clinical Oncology;43(14)
https://doi.org/10.1200/JCO-24-01334
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
