Predictive markers for pathological complete response (pCR) after neo-adjuvant chemotherapy in HER2-positive breast carcinoma

Histol Histopathol. 2024 Feb;39(2):153-164. doi: 10.14670/HH-18-626. Epub 2023 May 10.

Abstract

Objectives: Patients with HER2-positive invasive breast cancer that is node-positive and/or larger than 3 cm are generally treated with neoadjuvant chemotherapy (NAC). We aimed to identify predictive markers for pathological complete response (pCR) after NAC in HER2-positive breast carcinoma.

Methods: Hematoxylin/eosin-stained slides of 43 HER2-positive breast carcinoma biopsies were histopathologically reviewed. Immunohistochemistry (IHC) was performed on pre-NAC biopsies, comprising HER2, estrogen receptor (ER), progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), mucin-4 (MUC4), p53 and p63. Dual-probe HER2 in situ hybridization (ISH) was performed to study the mean HER2 and CEP17 copy numbers. ISH and IHC data were retrospectively collected for a validation cohort, comprising 33 patients.

Results: Younger age at diagnosis, 3+ HER2 IHC scores, high mean HER2 copy numbers and high mean HER2/CEP17 ratios were significantly associated with an increased chance of achieving a pCR, and the latter two associations were confirmed in the validation cohort. No other immunohistochemical or histopathological markers were associated with pCR.

Conclusions: This retrospective study of two community-based NAC-treated HER2-positive breast cancer patient cohorts identified high mean HER2 copy numbers as a strong predictor for pCR. Further studies on larger cohorts are required to determine a precise cut-point for this predictive marker.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Female
  • Humans
  • Neoadjuvant Therapy*
  • Receptor, ErbB-2 / analysis
  • Receptors, Progesterone / metabolism
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • Receptor, ErbB-2
  • Receptors, Progesterone