Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes

Mothaffar F. Rimawi, Priya B. Shetty, Heidi L. Weiss, Rachel Schiff, C. Kent Osborne, Gary C. Chamness, Richard M. Elledge

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

BACKGROUND: Epidermal growth factor receptor (EGFR) expression is associated with aggressive phenotypes in preclinical breast cancer models, but in clinical studies, EGFR has been inconsistently linked to poor outcome. We hypothesized that EGFR expression in human breast tumors, when centrally and uniformly assessed, is associated with an aggressive phenotype and resistance to systemic therapy. METHODS: In a database of 47,286 patients with breast cancer, EGFR status was known on 2567 tumors. EGFR levels were measured centrally by ligand binding assay, and tumors with ≥10 fmol/mg were prospectively deemed positive. Clinical and biological features of EGFR-positive and EGFR-negative tumors were compared. Clinical outcomes were assessed by systemic therapy status. RESULTS: Of 2567 tumors, 475 (18%) were EGFR positive. EGFR-positive tumors were more common in younger and in black women, were larger, had a higher S-phase fraction, and were more likely to be aneuploid. EGFR-positive tumors were more likely to be HER2-positive (26% vs 16%, P < .0001), but less likely to be estrogen receptor-positive (60% vs 88%, P < .0001) or progesterone receptor-positive (26% vs 65%, P < .0001). In multivariate analyses, EGFR expression independently correlated with worse disease-free survival (hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.4-2.41, P = .007) and overall survival (HR = 1.98, 95% CI, 1.36-2.88, P = .0004) in treated patients, but not in untreated patients. CONCLUSIONS: EGFR expression is more common in breast tumors in younger and black women. It is associated with lower hormone receptor levels, higher proliferation, genomic instability, and HER2 overexpression. It is correlated with higher risk of relapse in patients receiving adjuvant treatment. Blocking EGFR may improve outcome in selected patients.

Original languageEnglish (US)
Pages (from-to)1234-1242
Number of pages9
JournalCancer
Volume116
Issue number5
DOIs
StatePublished - Mar 1 2010

Keywords

  • Breast cancer
  • Chemotherapy resistance
  • EGFR
  • Resistance to endocrine therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes'. Together they form a unique fingerprint.

Cite this