Pathological complete response and survival according to the level of HER-2 amplification after trastuzumab-based neoadjuvant therapy for breast cancer

Br J Cancer. 2010 Oct 26;103(9):1335-42. doi: 10.1038/sj.bjc.6605939.

Abstract

Background: We analysed whether the level of human epidermal growth factor receptor-2 (HER-2) amplification significantly influenced either pathological complete response (pCR) or recurrence-free survival (RFS) and overall survival (OS) after trastuzumab-based neoadjuvant therapy.

Methods: In all, 99 patients with an HER-2-amplified breast tumour treated with trastuzumab-based neoadjuvant therapy were included. Tumours were classified as low amplified (LA; 6-10 signals per nuclei) or highly amplified (HA; >10 signals). Pathological response was assessed according to Chevallier's classification (pCR was defined as grade 1 or 2). Median follow-up lasted 46 months (6-83). Cox uni- and multivariate analyses were performed.

Results: In all, 33 tumour samples were LA and 66 were HA. The pCR in HA tumours was significantly higher than in LA tumours (55% vs 24%, P=0.005), whereas no association was found between the pCR rate and tumour stage, grade or hormone receptor status. In multivariate analysis, the pathological nodal status (P=0.005) and adjuvant trastuzumab (P=0.037) were independently associated with RFS, whereas the level of HER-2 amplification nearly reached statistical significance (P=0.057). There was no significant difference between LA and HA tumours for OS (P=0.22, log-rank).

Conclusion: The level of HER-2 gene amplification significantly influenced pCR but not RFS or OS in non-metastatic breast cancer treated with trastuzumab-based neoadjuvant therapy. However, RFS in patients with HA tumours tended to be shorter.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Gene Amplification
  • Genes, erbB-2*
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Remission Induction
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Trastuzumab