Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study.

Autor: Schettini F; Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.; Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain.; Department of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain., Blondeaux E; U.O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Molinelli C; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Bas R; Department of Medical Oncology, Universite Paris Cité, 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., Di Meglio A; Cancer Survivorship Group, INSERM U981, Gustave Roussy, Villejuif, France., Bernstein Molho R; Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center affiliated to Tel Aviv University, Tel Hashomer, Israel., Linn SC; Department of Medical Oncology, Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands., Pogoda K; Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland., Carrasco E; Hereditary Cancer Genetics Unit, Medical oncology Department, Vall d´Hebron University Hospital, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain., Punie K; Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium., Agostinetto E; Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B.), Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium., Lopetegui-Lia N; Department of Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA., Phillips KA; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.; Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia., Toss A; Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.; Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy., Rousset-Jablonski C; Department of Surgery, Leon Berard Cancer Center, Lyon, France.; Unité INSERM U1290, Université Claude Bernard Lyon 1, Lyon, France.; Hopital Femme Mère Enfant, Hospice civils de Lyon, Bron, France., Acheritogaray M; Department of Gynecology, Cote Basque Hospital Center, Bayonne, France., Ferrari A; Hereditary Breast and Ovarian Cancer (HBOC) Unit and General Surgery 3 - Senology, Breast Cancer Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.; University of Pavia, Pavia, Italy., Paluch-Shimon S; Sharett institute of oncology, Hadassah University Hospital & Faculty of Medicine, Hebrew University, Jerusalem, Israel., Fruscio R; UO Gynecology, Department of Medicine and Surgery, University of Milan-Bicocca, IRCCS San Gerardo dei Tintori, Monza, Italy., Cui W; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia., Wong SM; Stroll Cancer Prevention Centre, Jewish General Hospital, and McGill University Medical School, Montreal, Quebec, Canada., Vernieri C; Medical Oncology Department, Breast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.; Oncology and Hematology-Oncology Department, University of Milan, Milano, Italy., Dieci MV; Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università di Padova, Padova, Italy.; Oncologia 2, Istituto Oncologico Veneto IRCCS, Padova, Italy., Matikas A; Department of Oncology/Pathology, Karolinska Institute and Breast Center, Karolinska University Hospital, Stockholm, Sweden., Rozenblit M; Medical Oncology, Yale University, New Haven, Connecticut, USA., Villarreal-Garza C; Breast Cancer Center, Hospital Zambrano Hellion - TecSalud, Tecnologico de Monterrey, Monterrey, Mexico., De Marchis L; Division of Medical Oncology, Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.; Medical Oncology Department of Hematology, Oncology, Dermatology, Umberto 1 University Hospital, Rome, Italy., Puglisi F; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.; Department of Medicine, University of Udine, Udine, Italy., Vasconcelos de Matos L; Breast Cancer Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal., Mariño M; Hospital Universitari Son Espases Palma, Palma, Spain., Teixeira L; Department of Senology, Université Paris Cité, Assistance Publique-Hôpitaux de Paris, Saint Louis University Hospital, Paris, France., Graffeo R; Oncology Institute of Southern Switzerland, EOC-IOSI, Bellinzona, Switzerland., Rognone A; Department of Oncology, IRCCS Ospedale San Raffaele, Milano, Italy., Chirco A; Medical Oncology Unit, ASST Papa Giovanni XXIII, Bergamo, Italy., Antone N; Institute of Oncology 'Ion Chiricuta', Cluj-Napoca, Romania., Abdou Y; University of North Carolina - Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, USA., Marhold M; Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Božović-Spasojević I; Institute for Oncology and Radiology of Serbia, University of Belgrade, Faculty of Medicine, Belgrade, Serbia., Cortés Salgado A; Medical Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain., Carmisciano L; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Bruzzone M; U.O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genova, Italy., Curigliano G; Early Drug Development for Innovative Therapies Division, IRCCS European Institute of Oncology (IEO), Milan, Italy.; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy., Prat A; Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.; Department of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.; Institute of Cancer and Blood Disorders, Hospital Clinic of Barcelona, Barcelona, Spain.; Reveal Genomics, Barcelona, Spain.; Institute of Oncology (IOB)-Hospital Quirón Salud, Barcelona, Spain., Lambertini M; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
Jazyk: angličtina
Zdroj: Cancer [Cancer] 2024 Aug 15; Vol. 130 (16), pp. 2746-2762. Date of Electronic Publication: 2024 May 16.
DOI: 10.1002/cncr.35323
Abstrakt: Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset.
Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05.
Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS.
Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.
(© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
Databáze: MEDLINE
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