Clinicopathological Characteristics and Prognosis of HER2-Low Early-Stage Breast Cancer: A Single-Institution Experience

Hangcheng Xu; Yiqun Han; Yun Wu; Yan Wang; Qing Li; Pin Zhang; Peng Yuan; Yang Luo; Ying Fan; Shanshan Chen; Ruigang Cai; Qiao Li; Fei Ma; Binghe Xu; Jiayu Wang

doi:10.3389/fonc.2022.906011

Clinicopathological Characteristics and Prognosis of HER2-Low Early-Stage Breast Cancer: A Single-Institution Experience

Front Oncol. 2022 Jun 16:12:906011. doi: 10.3389/fonc.2022.906011. eCollection 2022.

Authors

Hangcheng Xu¹, Yiqun Han¹, Yun Wu¹, Yan Wang¹, Qing Li¹, Pin Zhang¹, Peng Yuan², Yang Luo¹, Ying Fan¹, Shanshan Chen¹, Ruigang Cai¹, Qiao Li¹, Fei Ma¹, Binghe Xu¹, Jiayu Wang¹

Affiliations

¹ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract

Background: Human epidermal growth factor 2 (HER2)-low breast cancer, which is defined as HER2 1+ or 2+ in immunohistochemistry without gene amplification, accounts for a considerable part of all breast cancers. However, it remains controversial whether HER2-low breast cancer is a distinct entity. Our aim was to compare the clinicopathological features and survival outcomes between HER2-zero and HER2-low early breast cancer.

Methods: The study was a retrospective analysis that enrolled 1,039 patients with available HER2 expression data in a single institute from 2013 to 2014, of whom 262 HER2-positive patients were excluded from the subsequent analysis. The remaining patients were divided into HER2-zero and HER2-low groups. Each group was further categorized into a hormone receptor (HR)-positive and an HR-negative subgroup. Clinicopathological characteristics were collected and compared between HER2-zero and HER2-low groups. The primary endpoint was disease-free survival (DFS) and overall survival (OS), which were analyzed using the Kaplan-Meier method with log-rank test, landmark analysis, and Cox proportional hazards model.

Results: A total of 777 non-HER2-positive patients were included in this analysis, of whom 126, 552, 53, and 46 patients were HR-positive/HER2-zero, HR-positive/HER2-low, HR-negative/HER2-zero, and HR-negative/HER2-low, respectively. No significant difference in DFS and OS was detected between the HER2-zero group and the HER2-low group when paired by HR status. Landmark analysis with a time point set at 5 years indicated that HR-positive/HER2-low patients had a better DFS compared with HR-positive/HER2-zero patients after 5 years (p = 0.0047). HER2-low status was an independent prognostic factor for DFS after 5 years [hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.13-0.75, p = 0.01].

Conclusion: The clinicopathological characteristics and prognosis of HER2-zero and HER2-low breast cancer were similar regardless of HR status. Patients with HR-positive/HER2-low tumors tended to have a better DFS than their HR-positive/HER2-zero counterparts after 5 years.

Keywords: HER2-low; HER2-zero; breast cancer; landmark analysis; prognosis.