Re-testing of predictive biomarkers on surgical breast cancer specimens is clinically relevant

Breast Cancer Res Treat. 2019 Apr;174(3):795-805. doi: 10.1007/s10549-018-05119-2. Epub 2019 Jan 18.

Abstract

Purpose: The accuracy of predictive and prognostic biomarker assessment in breast cancer is paramount since these guide therapy decisions. The aim was to investigate the concordance of biomarkers and immunohistochemical (IHC)-based surrogate tumor subtypes between core needle biopsies (CNB) and consecutive paired breast cancer surgical resections.

Methods: This retrospective study comprised two cohorts of patients with primary breast cancer diagnosed between 2016 and 2017: one treated with primary surgery (n = 526) and one with neoadjuvant chemotherapy (NAC) (n = 216). The agreement between preoperative CNB and paired tumor specimens regarding the assessment of biomarkers and surrogate tumor subtypes was evaluated in both cohorts.

Results: In the primary surgery cohort, the concordance rates and kappa values for estrogen receptor (ER), progesterone receptor (PR) and Ki67 were 98.6% (κ = 0.917), 89.3% (κ = 0.725) and 78.8% (κ = 0.529), respectively. Importantly, human epidermal growth factor receptor 2 (HER2) IHC assessment showed only moderate agreement (κ = 0.462). HER2 status combining IHC and in situ hybridization was discordant in 3.6% of cases, potentially impacting on indications for HER2-targeted therapy. The concordance rate for IHC-based surrogate tumor subtypes was only 73.2-78.3%. Generally lower concordance rates for ER, PR and HER2 were observed in the NAC cohort. Here, HER2 status was discordant in 7.4%.

Conclusions: The agreement of HER2 and Ki67 between CNB and paired surgical specimen in primary breast cancer is insufficient. Limited agreement of surrogate tumor subtypes indicates a significant clinical value of biomarker re-testing on surgical specimens.

Keywords: Breast cancer; Core biopsy; Human epidermal growth factor receptor 2; Immunohistochemistry; Ki67; Predictive biomarker.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Biopsy, Large-Core Needle
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery*
  • Drug Therapy
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Mastectomy / methods*
  • Middle Aged
  • Neoadjuvant Therapy
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2