Prognostic implications of HER2 changes after neoadjuvant chemotherapy in patients with HER2-zero and HER2-low breast cancer

HER2-Low Breast Cancer: Now and in the Future

“…Miglietta et al [ 24 ] showed that a HER2 transition was not significantly related to DFS, while the German Breast Group reported that patients with a HER2 transition from HER2-zero to HER2-low showed a significantly reduced invasive DFS compared with patients with a constant HER2-low status [ 46 ]. Kang et al [ 34 ] showed that patients with a HER2 transition from HER2-low to HER2-zero had better DFS and OS than patients with a constant HER2-zero status; however, when separately analyzed according to HR status, no significant differences in DFS or OS were observed. Due to limited evidence, currently, the prognostic role of a HER2 transition remains unknown, and further evaluation is necessary.…”

“…The mechanisms of a HER2 transition (HER2-low to HER2-zero or vice versa) have not been delineated well, but the possible reasons are as follows: (1) the intratumoral heterogeneity of breast cancer [ 47 - 49 ] and (2) therapeutic selection pressure after systemic treatment (including surgery, chemotherapy, hormonal therapy, and anti-HER2 therapy) [ 44 , 50 , 51 ]. Notably, patients with HR+/HER2-zero breast cancer have a higher probability of a HER2-low transition than patients with HR–/HER2-zero breast cancer in both early (OR, 2.48; 95% CI, 1.62 to 3.87) [ 34 ] and advanced settings (OR, 2.66; 95% CI, 1.12 to 6.59; p=0.027) [ 38 ], supporting the strong association between HR+ and HER2-low tumors in biology and that HR+ might affect changes in HER2 status. In conclusion, HER2-low breast cancer is not currently considered a new entity of breast cancer based on the cumulative evidence reported to date.…”