Neoadjuvant chemotherapy efficacy and prognosis in HER2-low and HER2-zero breast cancer patients by HR status: a retrospective study in China

PeerJ. 2024 May 29:12:e17492. doi: 10.7717/peerj.17492. eCollection 2024.

Abstract

Background: The promising efficacy of novel anti-HER2 antibody-drug conjugates (ADC) in HER2-low breast cancer has made HER2-low a research hotspot. However, controversy remains regarding the neoadjuvant chemotherapy (NAC) efficacy, prognosis, and the relationship with hormone receptor (HR) status of HER2-low.

Methods: A retrospective analysis was conducted on 975 patients with HER2-negative breast cancer undergoing NAC at Tianjin Medical University Cancer Institute and Hospital, evaluating pathological complete response (pCR) rate and prognosis between HER2-low and HER2-zero in the overall cohort and subgroups.

Results: Overall, 579 (59.4%) and 396 (40.6%) patients were HER2-low and HER2-zero disease, respectively. Compared with HER2-zero, the HER2-low cohort consists of more postmenopausal patients, with lower histological grade and higher HR positivity. In the HR-positive subgroup, HER2-low cases remain to exhibit lower histological grade, while in the HR-negative subgroup, they show higher grade. The HER2-low group had lower pCR rates than the HER2-zero group (16.4% vs. 24.0%). In the HR-positive subgroup, HER2-low consistently showed lower pCR rate (8.1% vs. 15.5%), and served as an independent suppressive factor for the pCR rate. However, no significant difference was observed in the pCR rates between HER2-low and HER2-zero in the HR-negative breast cancer. In the entire cohort and in stratified subgroups based on HR and pCR statuses, no difference in disease-free survival were observed between HER2-low and HER2-zero.

Conclusions: In the Chinese population, HER2-low breast cancer exhibits distinct characteristics and efficacy of NAC in different HR subgroups. Its reduced pCR rate in HR-positive subgroup is particularly important for clinical decisions. However, HER2-low is not a reliable factor for assessing long-term survival outcomes.

Keywords: Breast cancer; Disease-free survival; Human epidermal growth factor receptor 2; Neoadjuvant chemotherapy; Pathological complete response.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • China
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy*
  • Prognosis
  • Receptor, ErbB-2* / genetics
  • Receptor, ErbB-2* / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • Treatment Outcome

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Receptors, Estrogen
  • Receptors, Progesterone

Grants and funding

This study was supported by research funding from the General Project of the Scientific Research Program of the Tianjin Municipal Education Commission (Grant no. 2020KJ136). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.