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 differences 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-specific 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 significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific 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-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49-0.93; P = 0.019).

Conclusions: These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

Keywords: Breast cancer; HER2-low; Prognosis.

Fig. 1

Flow diagram for the selection of patients in this study

Fig. 2

OS and BCSS (A, B) in HR-positive breast cancer and (C, D) in TNBC. No significant difference was noted in overall survival between patients with HER2-low breast cancer and those with HER2-IHC 0 breast cancer, but breast cancer-specific survival was significantly better in patients with HER2-low breast cancer than in those with HER2-IHC 0 breast cancer

Fig. 3

Kaplan–Meier survival curves for BCSS stratified by pathological stage. A A significant association was observed between pathological stage and breast cancer-specific survival. Breast cancer-specific survival was significantly better in patients with HER2-low breast cancer than in those with HER2-IHC 0 breast cancer in stages I (B), II (C), and III (D)