Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study - 29/05/25

Doi : 10.1016/S1470-2045(25)00152-4

Eva Blondeaux, MD ^a,^{*
Contributed equally}, Amir Sonnenblick, MD ^b,^{*
Contributed equally}, Elisa Agostinetto, MD ^c, Raphaëlle Bas, MD ^d, Hee J Kim, ProfMD ^e, Maria A Franzoi, MD ^f,^g, Rinat Bernstein-Molho, MD ^h, Sabine Linn, MD ^i,^j, Ava Kwong, ProfPhD ^k,^l,^m, Katarzyna Pogoda, MD ⁿ, Judith Balmana, MD ^o, Ann Smeets, MD ^p, Jyoti Bajpai, MD ^q, Halle C F Moore, ProfMD ^r,^s, Ann H Partridge, MD ^t, Kelly-Anne Phillips, ProfMD ^u,^v, Angela Toss, MD ^w,^x, Christine Rousset-Jablonski, MD ^y,^z,^aa, Fedro A Peccatori, PhD ^ab, Tiphaine Renaud, MD ^ac, Alberta Ferrari, MD ^ad,^ae, Shani Paluch-Shimon, MD ^af, Pablo Mando, MD ^ag, Jeong E Lee, MD ^ah, Robert Fruscio, MD ^ai,^aj, Wanda Cui, MBBS ^u,^v, Stephanie M Wong, MD ^ak, Claudio Vernieri, MD ^al,^am, Kathryn J Ruddy, MD ^an, Maria V Dieci, MD ^ao,^ap, Alexios Matikas, MD ^aq, Mariya Rozenblit, MD ^ar, Deniz C Guven, MD ^as, Minna Lee, MD ^at, Cynthia Villarreal-Garza, MD ^au, Shelley E Hwang, MD ^av, Laura De Marchis, MD ^aw,^ax, Fabio Puglisi, MD ^ay,^az, Zoe Kemp, MD ^ba, Pedro A Meireles, MD ^bb, Anastasia Parokonnaya, MD ^bc, Gustavo Werutsky, MD ^bd, Maiko Okano, MD ^be,^bf, Hatem A Azim, MD ^bg, Kleida Mati, MD ^bh, Shoshana Rosenberg, ScD ^bi, Richard Gelber, PhD ^bj, Luca Boni, MD ^a, Matteo Lambertini, PhD ^bk,^bl,⁎

^a Clinical Trial Unit, Epidemiologia Clinica, Ospedale Policlinico San Martino, Genova, Italy

^b The Oncology Division, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

^c Université libre de Bruxelles, Hôpital Universitaire de Bruxelles, Institut Jules Bordet, Service de Oncologie, Brussels, Belgium

^d Department of Medical Oncology, Universite Paris Cité, Institut Curie, Paris, France

^e Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

^f Cancer Survivorship Group, Gustave Roussy, Villejuif, France

^g INSERM U981, Villejuif, France

^h Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center affiliated to Tel Aviv University, Tel Hashomer, Israel

ⁱ Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands

^j Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands

^k Hong Kong Hereditary Breast Cancer Family Registry, Hong Kong

^l Cancer Genetics Centre and Breast Surgery Centre, Hong Kong Sanatorium and Hospital, Hong Kong

^m Department of Surgery, The University of Hong Kong, Hong Kong

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

^o Hereditary Cancer Genetics Unit, Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain

^p Department of Surgical Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium

^q Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India

^r Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH, USA

^s Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH, USA

^t Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

^u Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

^v Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia

^w Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy

^x Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy

^y Department of Surgery, Leon Berard Cancer Center, Lyon, France

^z INSERM 1290 RESHAPE, Lyon, France

^aa Hôpital Femme Mère Enfant, Bron, France

^ab Gynecologic Oncology Department, European Institute of Oncology, Milan, Italy

^ac Cancer Genetics Unit, Bergonie Institute, Bordeaux, France

^ad Hereditary Breast and Ovarian Cancer Unit and General Surgery 3—Senology, Breast Cancer Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

^ae University of Pavia, Pavia, Italy

^af Sharett Institute of Oncology, Hadassah University Hospital and Faculty of Medicine, Hebrew University, Jerusalem, Israel

^ag SUMA Argentina

^ah Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea

^ai UO Gynecology, IRCCS San Gerardo dei Tintori, Monza, Italy

^aj Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy

^ak Department of Surgery and Oncology, Jewish General Hospital Segal Cancer Centre, Montreal, QC, Canada

^al Medical Oncology Department, Breast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

^am Oncology and Hematology-Oncology Department, University of Milan, Milan, Italy

^an Department of Oncology, Mayo Clinic, Rochester, MN, USA

^ao Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università di Padova, Padova, Italy

^ap Oncologia 2, Istituto Oncologico Veneto IRCCS, Padova, Italy

^aq Department of Oncology–Pathology, Karolinska Institute and Breast Center, Karolinska University Hospital, Stockholm, Sweden

^ar Yale University, Medical Oncology, Yale New Haven, CT, USA

^as Hacettepe University Cancer Institute, Ankara, Turkey

^at Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

^au Breast Cancer Center, Hospital Zambrano Hellion –TecSalud, Tecnologico de Monterrey, Monterrey, Mexico

^av Department of Surgery, Duke University, Durham, NC, USA

^aw Division of Medical Oncology, Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy

^ax Medical Oncology Unit Department of Hematology, Oncology, Dermatology Umberto I University Hospital, Rome, Italy

^ay Department of Medical Oncology, Centro di Riferimento Oncologico di Avano–CRO IRCCS, Aviano, Italy

^az Department of Medicine, University of Udine, Udine, Italy

^aaa Breast Medical Oncology and Cancer Genetics Units, Royal Marsden Hospital, London, UK

^aab Medical Oncology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisbon, Portugal

^aac National Medical Research Center of Oncology named after N N Blokhin of the Russian Ministry of Health, Moscow, Russia

^aad Hospital Moinhos de Vento, Porto Alegre, Brazil

^aae Hoshi General Hospital, Koriyama, Japan

^aaf Fukushima Medical University, Fukushima, Japan

^aag Cairo Cure Oncology Center, Cairo, Egypt

^aah SALUS Hospital, Tirana, Albania

^aai Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA

^aaj Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, USA

^aak Department of Medical Oncology, Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy

^aal Department of Internal Medicine and Medical Specialties, School of Medicine, University of Genova, Genova, Italy

^* Correspondence to: Dr Matteo Lambertini, Department of Medical Oncology, Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy Department of Medical Oncology Clinica di Oncologia Medica IRCCS Ospedale Policlinico San Martino Genova 16132 Italy

Summary

Background

Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer.

Methods

The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I–III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306.

Findings

Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7–12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53–0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61–18·17] with RRM vs 16·65 years [16·38–16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48–0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43–18·03] with RRSO vs 16·67 years [16·38–16·96] without RRSO).

Interpretation

In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies.

Funding

Italian Association for Cancer Research.

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Vol 26 - N° 6

P. 759-770 - juin 2025 Retour au numéro

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Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study - 29/05/25

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