HER2 immunohistochemical scores provide prognostic information for patients with HER2-type invasive breast cancer

Histopathology. 2019 Mar;74(4):578-586. doi: 10.1111/his.13801. Epub 2019 Jan 29.

Abstract

Aims: Invasive breast cancer patients with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) scores of 3+ or 2+ with reflex in-situ hybridisation (ISH) positivity are suitable for anti-HER2 therapies. The aim of this study is to investigate whether the prognoses between IHC 3+ patients and IHC 2+/ISH+ patients are different.

Methods and results: We analysed the clinicopathological information of 886 consecutive cases of HER2-positive early breast cancer. The influences of the patients' age, cancer stage, hormone receptor status and anti-HER2 treatment were adjusted using a multivariate Cox regression model. Both HER2 copy numbers and HER2 ISH ratios of the IHC 3+ group were significantly higher than those of the IHC 2+/ISH+ group. The outcomes of IHC 3+ patients were significantly better than those of IHC 2+/ISH+ patients in the univariate and multivariate analyses. HER2 copy numbers of ≥8 represented the best prognostic value, and it was chosen to be the cut-off value. The reflex ISH for IHC 2+ patients with high HER2 copy numbers (≥8) predicted a better overall survival than that for those with low HER2 copy numbers.

Conclusion: HER2 IHC scores and HER2 copy numbers can provide prognostic information for patients with HER2-positive invasive breast cancer. Both IHC 3+ and IHC 2+ patients with high HER2 copy numbers had a better prognosis.

Keywords: breast neoplasms; erbB-2; immunohistochemistry; in-situ hybridisation; prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / analysis
  • Receptor, ErbB-2 / biosynthesis*

Substances

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