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Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study.
Schettini, Francesco; Blondeaux, Eva; Molinelli, Chiara; Bas, Raphaëlle; Kim, Hee Jeong; Di Meglio, Antonio; Bernstein Molho, Rinat; Linn, Sabine C; Pogoda, Katarzyna; Carrasco, Estela; Punie, Kevin; Agostinetto, Elisa; Lopetegui-Lia, Nerea; Phillips, Kelly-Anne; Toss, Angela; Rousset-Jablonski, Christine; Acheritogaray, Marion; Ferrari, Alberta; Paluch-Shimon, Shani; Fruscio, Robert; Cui, Wanda; Wong, Stephanie M; Vernieri, Claudio; Dieci, Maria Vittoria; Matikas, Alexios; Rozenblit, Mariya; Villarreal-Garza, Cynthia; De Marchis, Laura; Puglisi, Fabio; Vasconcelos de Matos, Leonor; Mariño, Monica; Teixeira, Luis; Graffeo, Rossella; Rognone, Alessia; Chirco, Alessandra; Antone, Nicoleta; Abdou, Yara; Marhold, Maximilian; Bozovic-Spasojevic, Ivana; Cortés Salgado, Alfonso; Carmisciano, Luca; Bruzzone, Marco; Curigliano, Giuseppe; Prat, Aleix; Lambertini, Matteo.
Afiliación
  • Schettini F; Translational Genomics and Targeted Therapies in Solid Tumors group, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
  • Blondeaux E; Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain.
  • Molinelli C; Department of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
  • Bas R; U.O. Epidemiologia Clinica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
  • Kim HJ; Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy.
  • Di Meglio A; Department of Medical Oncology, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
  • Bernstein Molho R; Department of Medical Oncology, Universite Paris Cité, Institut Curie, Paris, France.
  • Linn SC; Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
  • Pogoda K; Cancer Survivorship Group, INSERM U981, Gustave Roussy, Villejuif, France.
  • Carrasco E; Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center affiliated to Tel Aviv University, Tel Hashomer, Israel.
  • Punie K; Department of Medical Oncology, Netherlands Cancer Institute (NKI), Amsterdam, The Netherlands.
  • Agostinetto E; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Lopetegui-Lia N; Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
  • Phillips KA; Hereditary Cancer Genetics Unit, Medical oncology Department, Vall d´Hebron University Hospital, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • Toss A; Department of General Medical Oncology and Multidisciplinary Breast Center, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium.
  • Rousset-Jablonski C; Institut Jules Bordet and l'Université Libre de Bruxelles (U.L.B.), Hôpital Universitaire de Bruxelles (HUB), Brussels, Belgium.
  • Acheritogaray M; Department of Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.
  • Ferrari A; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Paluch-Shimon S; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
  • Fruscio R; Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Cui W; Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
  • Wong SM; Division of Oncology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
  • Vernieri C; Department of Surgery, Leon Berard Cancer Center, Lyon, France.
  • Dieci MV; Unité INSERM U1290, Université Claude Bernard Lyon 1, Lyon, France.
  • Matikas A; Hopital Femme Mère Enfant, Hospice civils de Lyon, Bron, France.
  • Rozenblit M; Department of Gynecology, Cote Basque Hospital Center, Bayonne, France.
  • Villarreal-Garza C; Hereditary Breast and Ovarian Cancer (HBOC) Unit and General Surgery 3 - Senology, Breast Cancer Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • De Marchis L; University of Pavia, Pavia, Italy.
  • Puglisi F; Sharett institute of oncology, Hadassah University Hospital & Faculty of Medicine, Hebrew University, Jerusalem, Israel.
  • Vasconcelos de Matos L; UO Gynecology, Department of Medicine and Surgery, University of Milan-Bicocca, IRCCS San Gerardo dei Tintori, Monza, Italy.
  • Mariño M; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
  • Teixeira L; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, Victoria, Australia.
  • Graffeo R; Stroll Cancer Prevention Centre, Jewish General Hospital, and McGill University Medical School, Montreal, Quebec, Canada.
  • Rognone A; Medical Oncology Department, Breast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
  • Chirco A; Oncology and Hematology-Oncology Department, University of Milan, Milano, Italy.
  • Antone N; Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università di Padova, Padova, Italy.
  • Abdou Y; Oncologia 2, Istituto Oncologico Veneto IRCCS, Padova, Italy.
  • Marhold M; Department of Oncology/Pathology, Karolinska Institute and Breast Center, Karolinska University Hospital, Stockholm, Sweden.
  • Bozovic-Spasojevic I; Medical Oncology, Yale University, New Haven, Connecticut, USA.
  • Cortés Salgado A; Breast Cancer Center, Hospital Zambrano Hellion - TecSalud, Tecnologico de Monterrey, Monterrey, Mexico.
  • Carmisciano L; Division of Medical Oncology, Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy.
  • Bruzzone M; Medical Oncology Department of Hematology, Oncology, Dermatology, Umberto 1 University Hospital, Rome, Italy.
  • Curigliano G; Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy.
  • Prat A; Department of Medicine, University of Udine, Udine, Italy.
  • Lambertini M; Breast Cancer Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal.
Cancer ; 130(16): 2746-2762, 2024 Aug 15.
Article en En | MEDLINE | ID: mdl-38752572
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Mutación de Línea Germinal / Receptor ErbB-2 / Proteína BRCA1 / Proteína BRCA2 Límite: Adult / Female / Humans Idioma: En Revista: Cancer Año: 2024 Tipo del documento: Article País de afiliación: España
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Mutación de Línea Germinal / Receptor ErbB-2 / Proteína BRCA1 / Proteína BRCA2 Límite: Adult / Female / Humans Idioma: En Revista: Cancer Año: 2024 Tipo del documento: Article País de afiliación: España