Expression of EGFR in relation to BRCA1 status, basal-like markers and prognosis in breast cancer

Abstract

Aims: BRCA1-related breast cancer is associated with a basal-like phenotype, and is frequently estrogen receptor and HER2-negative. The expression of EGFR has been considered to be one component of the basal-like phenotype, but no standard criteria exist. We have studied the relationship between EGFR expression, BRCA1 status and basal markers with respect to clinico-pathological associations and prognosis, in addition to an evaluation of different criteria for EGFR assessment by immunohistochemistry.

Methods: A tissue microarray comprising 230 available cases from our series of primary invasive breast cancer diagnosed in Ashkenazi Jewish women during 1980-1995, was stained for EGFR using the Dako PharmDX kit, and evaluated by Webslide virtual microscopy.

Results: EGFR was positive in 9-19% according to different criteria. Expression was associated with BRCA1 carrier status and basal-like markers as negative ER, positive CK 5/6 and positive P-cadherin staining. EGFR was prognostically significant by univariate and multivariate analysis within the group carrying germ-line BRCA1 mutations. Histological grade, axillary lymph node status and P-cadherin status had significant independent value in the final multivariate model including all cases, whereas EGFR was not significant in this model. All five scoring systems gave comparable results concerning clinico-pathological associations and patient outcome, although the most restrictive criteria (EGFR-HI) tended to be most sensitive in predicting BRCA1-status, a basal phenotype, and patient prognosis.

Conclusions: EGFR expression, being present in 9-19% of the cases, was prognostically significant among BRCA1 mutated cases only. In multivariate survival analysis of all cases, no independent effect was seen. Still, EGFR immunostaining might be relevant to predict the response to targeted therapy, and this should be studied further.