The emerging predictive and prognostic role of HER2 in HER2-negative early breast cancer: a retrospective study

Breast Cancer Res Treat. 2024 Aug;206(3):603-614. doi: 10.1007/s10549-024-07336-4. Epub 2024 May 14.

Abstract

Purpose: Many patients with early breast cancer (eBC) undergoing neoadjuvant chemotherapy do not achieve pathological complete response (pCR), which is a prognostic factor. We examined the role of HER2-low expression in predicting pCR and prognosis in HER2-negative eBC.

Methods: We evaluated patients with stage I-III HER2-negative BC, treated between 2013 and 2023 at The Royal Marsden NHS Foundation Trust, London. Tumors were classified based on estrogen receptor (ER) status and into HER2-low and HER2-zero subgroups. We analyzed pCR rates, relapse-free survival (RFS) and overall survival (OS).

Results: 754 patients were included in the analysis. pCR rate was 8.9% in the ER+ /HER2-low, 16.5% in the ER+ /HER2-zero, 38.9% in the ER- ER-/HER2-low and 35.9% in the ER-/HER2-zero eBC (p < 0.001). Multivariable analysis showed a significantly lower pCR rate in HER2-low compared to HER2-zero BC in the ER+ subgroup. At a median follow-up of 63.8 months (59.9-67.4), we observed longer OS in HER2-low compared to HER2-zero patients in the overall and in the ER+ population. There was no predictive or prognostic impact of HER2-low status in the ER- population.

Conclusion: This study supports the interpretation of HER2 status as a possible prognostic and predictive biomarker for HER2-negative eBC, especially among patients with ER+ disease.

Keywords: Early breast cancer; Human Epidermal Growth Factor Receptor 2 (HER2); Pathological complete response (pCR); Prognosis.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Staging*
  • Prognosis
  • Receptor, ErbB-2* / genetics
  • Receptor, ErbB-2* / metabolism
  • Receptors, Estrogen* / metabolism
  • Retrospective Studies

Substances

  • Receptor, ErbB-2
  • ERBB2 protein, human
  • Biomarkers, Tumor
  • Receptors, Estrogen