Differences in treatment response and survival between HER2(2+)/FISH-positive and HER2(3+) breast cancer patients

Sicheng Zhou1, Xuhui Qin2, Wei Xing3

  • 1Department of Thyroid and Breast Surgery, Peking University First Hospital, Beijing, China.

Frontiers in Oncology
|April 21, 2025
PubMed
Abstract

Insights

Patients with HER2(3+) breast cancer (BC) show better response to dual-target neoadjuvant therapy (NAT) than HER2(2+)/FISH-positive BC. HER2 expression level impacts treatment efficacy and prognosis in HER2-positive BC patients.

Area of Science:

  • Oncology
  • Medical Research
  • Clinical Trials

Background:

  • Dual-target neoadjuvant therapy (NAT) is effective for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC).
  • Differences in response and prognosis exist between HER2(3+) and HER2(2+)/fluorescence in situ hybridization (FISH)-positive BC after TCbHP-based dual-target NAT.

Purpose of the Study:

  • To compare treatment responses and prognosis in HER2(3+) versus HER2(2+)/FISH-positive breast cancer patients undergoing dual-target NAT.
  • To identify factors influencing pathological complete response (pCR) and invasive disease-free survival (IDFS) in HER2-positive BC.

Main Methods:

  • Retrospective analysis of HER2-positive invasive BC patients receiving NAT and surgery (January 2019 - December 2022).
  • Propensity score matching (PSM) applied to 308 patients, resulting in 132 matched pairs (66 pairs).
  • Evaluation of pathological complete response (pCR) and invasive disease-free survival (IDFS).

Main Results:

  • The pCR rate was significantly higher in the HER2(3+) group compared to the HER2(2+)/FISH-positive group (P<0.001).
  • Tumor grade, hormone receptor (HR) status, and HER2 status significantly affected pCR.
  • The 3-year IDFS rate was better for HER2(3+) BC patients, though not statistically significant (P=0.083). Positive lymph nodes, HER2(3+), and pCR were independent prognostic factors for IDFS.

Conclusions:

  • HER2(2+)/FISH-positive BC patients demonstrated poorer treatment response and prognosis compared to HER2(3+) patients after dual-target NAT.
  • HER2 expression level is a critical determinant of therapeutic efficacy and patient prognosis in HER2-positive breast cancer treated with TCbHP-based dual-target NAT.