RESPONSE: Re: Germline BRCA1 Mutations and a Basal Epithelial Phenotype in Breast Cancer

Extract

We note with interest that data from Palacios et al. broadly support our original observation, and that the data from van der Groep et al. extend our findings to include other basal-associated markers, in this case, epidermal growth factor receptor (EGFR). It is notable that van der Groep et al. found that BRCA2-related breast cancers also tended to share the basal epithelioid phenotype previously identified only in BRCA1-related breast cancers. This result should be interpreted cautiously, particularly because only four tumors were studied and because all four BRCA2 tumors were estrogen receptor (ER)-negative, which is unusual. Most BRCA2-related breast cancers are ER-positive (1). Moreover, the reports of Sørlie et al. (2) and Palacios et al. do not suggest that the basal phenotype of BRCA1-related breast cancer is likely to be extendible to BRCA2-related breast cancer.

The data provided by Palacios et al. suggest that the complete ER/erbB2–negative, cytokeratin (CK) 5/6-positive phenotype may not be quite so discriminatory of a BRCA1 mutation if age is taken into account. However, in light of our findings and those reported by Palacios et al. and van der Groep et al. we suggest that basal markers, such as CK5/6 and its partner CK14, as well as P-cadherin and EGFR, be evaluated further as first-line immunohistochemical tests for the presence of a germ-line BRCA1 mutation. The finding of van der Groep et al. that the BRCA1-related basal phenotype can be extended to include the basal-associated marker EGFR is consistent with the work of Santini et al. (3), who noted that EGFR expression was frequently observed only in breast cancers with a high nuclear grade that also expressed basal epithelial markers (3). In a more recent study, long-term treatment of basal mammary epithelial cells with EGF resulted in a mobile rather than a stationary phenotype (4), possibly indicating a mechanism by which expression of EGFR influences the behavior of breast cancer cells that possess a basal epithelial phenotype.