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.
In a database of 47,286 patients with breast cancer, EGFR status was known on 2,567. 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 negative tumors were compared. Clinical outcomes were assessed by systemic therapy status.
475 out of 2,567 tumors (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<0.0001), but less likely to be ER-positive (60% vs. 88%, p<0.0001), or PR-positive (26% vs. 65%, p<0.0001).
In multivariate analyses, EGFR expression independently correlated with worse DFS (HR=1.66, 95% CI=1.4–2.41, p=0.007) and OS (HR=1.98, 95% CI=1.36–2.88, p=0.0004) in treated patients, but not in untreated patients.
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 over-expression. It is correlated with higher risk of relapse in patients receiving adjuvant treatment. Blocking EGFR may improve outcome in selected patients.