Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma

TLDR

Breast carcinomas are classified into ER⁺/luminal, normal breast‑like, HER2‑overexpressing, and basal‑like groups, with HER2‑overexpressing and basal‑like subtypes linked to poorer outcomes. The study aimed to develop a clinical assay to identify basal‑like breast tumors. The authors identified immunohistochemical markers by testing known basal‑like tumors and validated their prognostic relevance using tissue microarrays. A four‑antibody panel (ER, HER1, HER2, CK5/6) accurately identifies basal‑like breast cancers, with basal cytokeratin and HER1 expression associated with poorer survival, while c‑KIT is more frequent but not prognostic, suggesting potential HER1‑targeted therapies.

Abstract

Abstract Purpose: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)+/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER+/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors. Experimental Design: To identify an immunohistochemical profile for breast basal-like tumors, we collected a series of known basal-like tumors and tested them for protein patterns that are characteristic of this subtype. Next, we examined the significance of these protein patterns using tissue microarrays and evaluated the prognostic significance of these findings. Results: Using a panel of 21 basal-like tumors, which was determined using gene expression profiles, we saw that this subtype was typically immunohistochemically negative for estrogen receptor and HER2 but positive for basal cytokeratins, HER1, and/or c-KIT. Using breast carcinoma tissue microarrays representing 930 patients with 17.4-year mean follow-up, basal cytokeratin expression was associated with low disease-specific survival. HER1 expression was observed in 54% of cases positive for basal cytokeratins (versus 11% of negative cases) and was associated with poor survival independent of nodal status and size. c-KIT expression was more common in basal-like tumors than in other breast cancers but did not influence prognosis. Conclusions: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity. These studies show that many basal-like tumors express HER1, which suggests candidate drugs for evaluation in these patients.