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Publications

Journal Article Epublish

PubMed: 42646839 DOI: 10.1001/jamanetworkopen.2026.30856

Surgical Management of Early-Onset Breast Cancer Among Young BRCA1 and BRCA2 Carriers.

JAMA Netw Open 9(8):e2630856

Authors: Stephanie M Wong, Eva Blondeaux, Virginia Delucchi, Florence Coussy, Rinat Bernstein Molho, Sabine Linn, Antonio Di Meglio, Ava Kwong, Katarzyna Pogoda, Elisa Agostinetto, Ines Nevelsteen, Judith BalmaƱa, Halle C F Moore, Angela Toss, Alberta Ferrari, Christine Rousset-Jablonski, Tiphaine Renaud, Kelly-Anne Phillips, Fedro A Peccatori, Maria Agustina Ipina, Shani Paluch-Shimon, Jai Min Ryu, Wanda Cui, Minna Lee, Robert Fruscio, Mariya Rozenblit, Claudio Vernieri, Alexios Matikas, Maria Vittoria Dieci, Fergus J Couch, Laura De Marchis, Shelley E Hwang, Dione Aguilar Y Mendez, Deniz Can Guven, Monique Swain, Caterina Gianni, Stefano Spinaci, Giacomo Montagna, Matteo Lambertini, Hee Jeong Kim

Affiliations

  • Department of Surgery and Oncology, McGill University Medical School, Montreal, Quebec, Canada.
  • Stroll Cancer Prevention Centre, Jewish General Hospital Segal Cancer Centre, Montreal, Quebec, Canada.
  • AOM - IRCCS Ospedale Policlinico San Martino, Clinical Trial Unit, U.O. Epidemiologia Clinica, Genova Italy.
  • Department of Medical Oncology, Institut Curie-Institut of Women's Cancers, Paris, France.
  • Suzanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center affiliated with Tel Aviv University, Tel Hashomer, Israel.
  • Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Cancer Survivorship Team, UniversitĆ© Paris-Saclay, UVSQ, Gustave Roussy, Inserm, CESP, F-94800, Villejuif, France.
  • Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong.
  • Cancer Genetics Centre and Breast Surgery Centre, Hong Kong Sanatorium and Hospital, Hong Kong.
  • Department of Surgery, The University of Hong Kong, Hong Kong.
  • Department of Breast Cancer and Reconstructive Surgery, Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
  • UniversitĆ© Libre de Bruxelles, HĆ“pital Universitaire de Bruxelles, Institut Jules Bordet, Service de Oncologie, Brussels, Belgium.
  • Department of Surgical Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
  • Hereditary Cancer Genetics Unit, Medical Oncology Department, Vall dĀ“Hebron University Hospital, Vall dĀ“Hebron Institute of Oncology, Barcelona, Spain.
  • Department of Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
  • Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
  • Hereditary Breast and Ovarian Cancer Unit and General Surgery 3-Senology, Breast Cancer Center, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy.
  • University of Pavia, Pavia, Italy.
  • Department of Surgery, Leon Berard Cancer Centre, Centre LĆ©on BĆ©rard, Lyon, France.
  • INSERM U1290 RESHAPE, Lyon, France.
  • Gynecology and Obstetrics Department, HĆ“pital Femme MĆØre Enfant, Hospices Civils de Lyon, France.
  • Cancer Genetics Unit, Bergonie Institute, Bordeaux, France.
  • Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
  • Gynecologic Oncology Department, European Institute of Oncology (Istituto di Ricovero e Cura a Carattere Scientifico [IRCCS]), Milan, Italy.
  • SUMA (Grupo Cooperativo Argentino para el Estudio y la InvestigaciĆ³n del CĆ”ncer de Mama), Argentina.
  • Sharett Institute of Oncology, Hadassah University Hospital and The Faculty of Medicine, Hebrew University, Jerusalem, Israel.
  • Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea.
  • Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
  • UO Gynecology, Department of Medicine and Surgery, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Gerardo dei Tintori, Monza, Italy.
  • Department of Obstetrics and Gynecology, University of Milan-Bicocca, Monza, Italy.
  • Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut.
  • Medical Oncology Department, Breast Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Nazionale dei Tumori, Milano, Italy.
  • Department of Oncology, UniversitĆ  La Statale, Milano, Italy.
  • Department of Oncology-Pathology, Karolinska Institute and Breast Center, Karolinska University Hospital, Stockholm, Sweden.
  • Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, UniversitĆ  di Padova, Padova, Italy.
  • Oncologia 2, Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
  • Division of Medical Oncology, Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
  • Medical Oncology, Unit Department of Hematology, Oncology, and Dermatology, Umberto I University Hospital, Rome, Italy.
  • Department of Surgery, Duke University, Durham, North Carolina.
  • Breast Cancer Center, Hospital Zambrano Hellion-TecSalud, Tecnologico de Monterrey, Monterrey, Mexico.
  • Hacettepe University Cancer Institute, Ankara, Turkey.
  • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
  • Henry Ford Hospital, Obstetrics and Gynecology Residency Program, Michigan State University, Detroit, Michigan.
  • Department of Clinical and Experimental Oncology and Hematology, Medical Oncology, Breast & GYN Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
  • Breast Surgery, Ospedale Villa Scassi-ASL3, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Metropolitana, Genova, Italy.
  • Department of Internal Medicine and Medical Specialties (DiMi), School of Medicine, University of Genova, Genova, Italy.
  • Academic Medical Oncology Unit, Ente Ospedaliero Ospedali Galliera, Genova, Italy.
  • Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Abstract

IMPORTANCE

Young BRCA carriers may undergo breast-conserving surgery (BCS) or mastectomy with or without contralateral risk-reducing mastectomy at the time of an index breast cancer diagnosis. A variety of factors may influence surgical decision-making.

OBJECTIVE

To explore surgical patterns of care and factors associated with uptake of bilateral mastectomy among affected BRCA1 or BRCA2 (BRCA1/2) carriers diagnosed with early-onset breast cancer.

DESIGN, SETTING, AND PARTICIPANTS

The BRCA BCY Collaboration is an international, hospital-based retrospective cohort study conducted at 109 centers across 5 continents. Women aged 40 years or younger with germline pathogenic or likely pathogenic variants in BRCA1/2 who were diagnosed between January 1, 2000, and December 31, 2020, with invasive stage I to III breast cancer were included. Data were collected between January 2022 and June 2024, and analyses were performed between May 21 and 28, 2025.

MAIN OUTCOME AND MEASURES

The main outcome was the evaluation of surgical management as primary treatment for a first diagnosis of invasive breast cancer, defined as BCS, unilateral mastectomy, or bilateral mastectomy.

RESULTS

Of 5660 eligible BRCA1/2 carriers, 4715 women (median [IQR] age, 35 [31-38] years) had unilateral stage I to III breast cancer with surgical treatment details available. In the cohort, 1805 patients (38.3%) underwent BCS, 1752 (37.2%) underwent unilateral mastectomy, and 1158 (24.6%) underwent bilateral mastectomy. The proportion of BRCA1/2 carriers undergoing BCS decreased over the study period (55.7% [49 of 88] in 2000 vs 27.0% [82 of 304] in 2020), whereas the use of bilateral mastectomy significantly increased (8.0% [7 of 88] in 2000 vs 44.4% [135 of 304] in 2020). Bilateral mastectomy was more common in women who had genetic testing performed before (248 of 435 [57.0%]) or within 6 months (729 of 1892 [38.5%]) of a breast cancer diagnosis compared with those tested after diagnosis (111 of 2167 [5.1%]). On multivariable analysis, compared with those tested after diagnosis, earlier genetic testing was the factor most strongly associated with bilateral mastectomy receipt (testing prior to diagnosis: adjusted odds ratio, 20.72 [95% CI, 15.27-28.13]; testing at diagnosis: adjusted odds ratio, 6.83 [95% CI, 5.39-8.66]). In subgroup analyses, including 2327 patients who had genetic testing performed before or within 6 months of diagnosis, 977 (42.0%) underwent bilateral mastectomy, with the lowest rates reported in Asia and Africa (130 of 499 [26.1%]) and the highest rates reported in North America (233 of 351 [66.4%]).

CONCLUSIONS AND RELEVANCE

The findings of this cohort study of young BRCA1/2 carriers suggest that geographic region and timing of genetic testing were the factors most strongly associated with surgical management.

MeSH

Research Design, Mastectomy, Genetic Testing, Breast Neoplasms, Neoplasms, Cohort Studies, Clinical Medicine, Odds Ratio, Breast, Diagnosis, Therapeutics, Genes, Brca2, Genes, Brca1