The association between HER2-low expression and prognosis of breast cancer: a systematic review and meta-analysis

Yuyao Tang; Guoshuang Shen; Yuanfang Xin; Zhoujuan Li; Yonghui Zheng; Miaozhou Wang; Zhen Liu; Yi Zhao; Fuxing Zhao; Dengfeng Ren; Jiuda Zhao

doi:10.1177/17588359231156669

The association between HER2-low expression and prognosis of breast cancer: a systematic review and meta-analysis

Ther Adv Med Oncol. 2023 Mar 1:15:17588359231156669. doi: 10.1177/17588359231156669. eCollection 2023.

Authors

Yuyao Tang¹, Guoshuang Shen¹, Yuanfang Xin¹, Zhoujuan Li¹, Yonghui Zheng¹, Miaozhou Wang¹, Zhen Liu¹, Yi Zhao¹, Fuxing Zhao¹, Dengfeng Ren¹, Jiuda Zhao^{2

1}

Affiliations

¹ Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, China.
² Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining 810000, China.

Abstract

Background: The use of antibody-drug conjugates for the treatment of advanced-stage human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer (BC) has shown prominent curative effects, which has led to increased academic interest. However, the role of HER2-low expression in the prognosis of BC remains controversial.

Methods: We conducted a systematic search of the PubMed, Embase, and Cochrane library databases and several oncology conferences until 20 September 2022. We used fixed- and random-effects models to calculate odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and pathological complete response (pCR) rates.

Results: Overall, 26 studies encompassing 677,248 patients were included in the meta-analysis. Patients with HER2-low BC showed significantly better OS than those with HER2-zero BC in the overall population (HR = 0.90; 95% CI: 0.85-0.97) and hormone receptor-positive population (HR = 0.98; 95% CI: 0.96-0.99), whereas no significant difference was observed in the OS of the hormone receptor-negative population (p > 0.05). In addition, there was no significant difference in the DFS of the overall and hormone receptor-negative population (p > 0.05), but better DFS than those with HER2-zero BC in the hormone receptor-negative population (HR = 0.96; 95% CI: 0.94-0.99). There was also no significant difference in the PFS of the overall population, hormone receptor-positive, and hormone receptor-negative population (p > 0.05). Patients with HER2-low BC had a lower pCR rate after neoadjuvant treatment than those with HER2-zero BC.

Conclusions: Compared to patients with HER2-zero BC, those with HER2-low BC had better OS in the overall population and hormone receptor-positive population, DFS in hormone receptor-positive population and lower pCR in the overall population. The biological differences between HER2-low and HER2-zero BCs, particularly in hormone receptor-positive patients, and the relationship between HER2-low expression status and prognosis need to be explored further.

Keywords: HER2-low; antibody–drug conjugates; breast cancer; overall survival; prognosis.