Association between human epidermal growth factor receptor 2 status, namely low and zero expression, and prognosis in hormone receptor-positive breast cancer: a single-center retrospective study

Yuki Hara; Hiroshi Yano; Yuka Ishida; Keisuke Iwasaki; Rin Yamaguchi

doi:10.21037/tcr-23-2216

Association between human epidermal growth factor receptor 2 status, namely low and zero expression, and prognosis in hormone receptor-positive breast cancer: a single-center retrospective study

Transl Cancer Res. 2024 Apr 30;13(4):1773-1785. doi: 10.21037/tcr-23-2216. Epub 2024 Apr 7.

Authors

Yuki Hara¹, Hiroshi Yano¹, Yuka Ishida¹, Keisuke Iwasaki², Rin Yamaguchi³

Affiliations

¹ Department of Breast Surgery, Sasebo City General Hospital, Nagasaki, Japan.
² Department of Pathology, Sasebo City General Hospital, Nagasaki, Japan.
³ Department of Pathology, Nagasaki University Hospital, Nagasaki, Japan.

Abstract

Background: The recently developed anti-human epidermal growth factor receptor 2 (HER2) therapy has substantially improved the prognosis of HER2-positive breast cancer. The DESTINY-Breast04 trial results showed that trastuzumab deruxtecan (T-DXd) significantly prolonged the survival of patients with HER2-low breast cancer, thus presenting a paradigm shift in anti-HER2 therapy. This may facilitate a change in the treatment strategy for HER2-low breast cancer. However, the implication of HER2-low in hormone receptor (HR)-positive breast cancer is unclear. In this retrospective study, we aimed to reveal the association between HER2 status, namely HER2-low and HER2-zero, and prognosis in HR-positive breast cancer.

Methods: We collected the data of 247 patients with estrogen receptor (ER)-positive/HER2-negative breast cancer (159 with HER2-low and 88 with HER2-zero breast cancer) who underwent surgery. Patients were divided into HER2-low and HER2-zero groups. Univariate analysis was performed to evaluate the baseline characteristics using the Wilcoxon rank sum test and Fisher's exact test. Survival analysis of the HER2-low and HER2-zero groups was performed using the Kaplan-Meier method.

Results: The median observation period was 2,706 days, and the median period until recurrence was 1,380 days; 25 patients (10%) had recurrences. Age (P=0.004) and menopausal status (P=0.04) were significant variables in the univariate analysis of baseline characteristics. In the subgroup analysis of luminal A- and B-like breast cancers, there was a significant difference in overall survival (OS) only in patients with luminal A-like breast cancer, but relapse-free survival (RFS) of the HER2-low luminal B-like cancer subgroups tended to be relatively short.

Conclusions: We inferred that the HER2-low and HER2-zero statuses do not affect the RFS and OS of patients with ER-positive breast cancer. The prognostic significance of HER2-low or HER2-zero status in luminal A- and B-like breast cancers might differ, and a new treatment strategy is required for the HER2-low subgroup.

Keywords: Human epidermal growth factor receptor 2 (HER2); breast cancer; overall survival (OS); relapse-free survival (RFS); trastuzumab deruxtecan (T-DXd).