HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis

Cancer Treat Rev. 2020 Mar:84:101965. doi: 10.1016/j.ctrv.2020.101965. Epub 2020 Jan 17.

Abstract

Background: HER2-positive (HER2+) breast cancer (BC) comprises all the four PAM50 molecular subtypes. Among these, the HER2-Enriched (HER2-E) appear to be associated with higher pathological complete response (pCR) rates following anti-HER2-based regimens. Here, we present a meta-analysis to validate the association of the HER2-E subtype with pCR following anti-HER2-based neoadjuvant treatments with or without chemotherapy (CT).

Methods: A systematic literature search was performed in February 2019. The primary objective was to compare the association between HER2-E subtype (versus others) and pCR. Selected secondary objectives were to compare the association between 1) HER2-E subtype and pCR in CT-free studies, 2) HER2-E subtype within hormone receptor (HR)-negative and HR+ disease and 3) HR-negative disease (versus HR+) and pCR in all patients and within HER2-E subtype. A random-effect model was applied. The Higgins' I2 was used to quantify heterogeneity.

Results: Sixteen studies were included, 5 of which tested CT-free regimens. HER2-E subtype was significantly associated with pCR in all patients (odds ratio [OR] = 3.50, p < 0.001, I2 = 33%), in HR+ (OR = 3.61, p < 0.001, I2 = 1%) and HR-negative tumors (OR = 2.28, p = 0.01, I2 = 47%). In CT-free studies, HER2-E subtype was associated with pCR in all patients (OR = 5.52, p < 0.001, I2 = 0%) and in HR + disease (OR = 4.08, p = 0.001, I2 = 0%). HR-negative status was significantly associated with pCR compared to HR + status in all patients (OR = 2.41, p < 0.001, I2 = 30%) and within the HER2-E subtype (OR = 1.76, p < 0.001, I2 = 0%).

Conclusions: The HER2-E biomarker identifies patients with a higher likelihood of achieving a pCR following neoadjuvant anti-HER2-based therapy beyond HR status and CT use. Future trial designs to escalate or de-escalate systemic therapy in HER2+ disease should consider this genomic biomarker.

Keywords: Biomarker; Breast cancer; HER2-Enriched; HER2-positive; PAM50; Pathologic complete response.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Female
  • Humans
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Remission Induction

Substances

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