Clinical characteristics and treatment outcomes of HER2 mutation and HER2 fusion in 22 patients with advanced breast cancer

Abstract

Abstract Background The clinical characteristics and efficacy of human epidermal growth factor receptor‐2 (HER‐2)‐directed agents against HER2 mutations and HER2 fusions in breast cancer are obscure due to their low frequency. Methods We conducted a retrospective study in patients with advanced breast cancer harboring HER2 mutations and/or HER2 fusions between January 1, 2017 and January 1, 2021. Results Among a total of 22 patients, 17 HER2 mutations were detected, including L755S, S310F, R100=, V777L, R897W, T862A, 440‐17C > G, H878Y, V842I, 73 + 9G > C, T278fs, E1069K, L755P, 226‐11C > T, 574 + 12C>T, L114V and P128L. The majority of patients had ductal carcinoma, which mostly coexisted with HER2 amplification/overexpression. The median progression‐free survival (PFS) of the 22 patients was 6.9 months (95% CI: 4.7, 9.1) in the first‐line setting. The median PFS of patients who received first‐line trastuzumab‐based regimens was significantly longer than that of patients who received a first‐line tyrosine kinase inhibitor (TKI) (10.8 months [95% CI: 2.9, 18.7] vs. 1.9 months [95% CI: 0.8, 3.0], p < 0.005). A total of 14 patients were treated with anti‐HER2 antibody‐drug conjugate (ADC), among whom the median treatment line of first‐time of administration of anti‐HER2 ADC was 4.5 (range, 1–10). Anti‐HER2 ADC reached an objective response rate (ORR) of 42.9%, a disease control rate (DCR) of 85.7% and a median PFS of 7.3 months (95% CI: 4.4–10.1) from the first‐time of administration. Conclusion Our data demonstrated the clinical benefit of anti‐HER2 treatment in Chinese breast cancer patients harboring HER2 mutation and/or HER2 fusion. The value of immunotherapy and treatment selection among individual HER2 variants needs further study.

Keywords

• anti‐HER2 therapy
• breast cancer
• HER2 fusion
• HER2 mutation