Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society

Abstract

Background: There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody–drug conjugates. We explored the diferences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. Methods: Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan–Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specifc survival between the two groups. Results: HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was signifcantly associated with a lower Ki-67 labeling index. No signifcant diference was observed in overall survival between the two groups. HER2-low breast cancer showed signifcantly better breast cancer-specifc survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specifc survival was signifcant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49–0.93; P=0.019). Conclusions: These fndings suggest that the biology and clinical impact of low HER2 expression can difer according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.