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

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; Mari&#241;o, M; Teixeira, L; Graffeo, R; Rognone, A; Chirco, A; Antone, N; Abdou, Y; Marhold, M; Božović-Spasojević, I; Cort&#233;s Salgado, A; Carmisciano, L; Bruzzone, M; Curigliano, G; Prat, A; Lambertini, M

Author(s): 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; Lambertini, M;
Details: Publication Year 2024-08-15,Volume 130,Issue #16,Page 2746-2762
Journal Title: Cancer
Publication Type: Research article
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.
Publisher: Wiley
Keywords: Humans; Female; *Receptor, ErbB-2/genetics/metabolism; Retrospective Studies; Adult; *Germ-Line Mutation; *Breast Neoplasms/genetics/pathology/mortality; *BRCA1 Protein/genetics; *BRCA2 Protein/genetics; Young Adult; Disease-Free Survival; Prognosis; Brca; HER2‐low; breast cancer; subtypes; young women
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1002/cncr.35323
Open Access at Publisher's Site: https://doi.org/10.1002/cncr.35323
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-09-03 07:48:57

Last Modified: 2024-09-03 07:49:09