1. Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study.
- Author
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Schettini F, Blondeaux E, Molinelli C, Bas R, Kim HJ, Di Meglio A, Bernstein Molho R, Linn SC, Pogoda K, Carrasco E, Punie K, Agostinetto E, Lopetegui-Lia N, Phillips KA, Toss A, Rousset-Jablonski C, Acheritogaray M, Ferrari A, Paluch-Shimon S, Fruscio R, Cui W, Wong SM, Vernieri C, Dieci MV, Matikas A, Rozenblit M, Villarreal-Garza C, De Marchis L, Puglisi F, Vasconcelos de Matos L, Mariño M, Teixeira L, Graffeo R, Rognone A, Chirco A, Antone N, Abdou Y, Marhold M, Božović-Spasojević I, Cortés Salgado A, Carmisciano L, Bruzzone M, Curigliano G, Prat A, and Lambertini M
- Subjects
- Humans, Female, Retrospective Studies, Adult, Young Adult, Disease-Free Survival, Prognosis, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Germ-Line Mutation, Breast Neoplasms genetics, Breast Neoplasms pathology, Breast Neoplasms mortality, BRCA1 Protein genetics, BRCA2 Protein genetics
- 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., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
- Published
- 2024
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