FOXA1 in Breast Cancer: A Luminal Marker with Promising Prognostic and Predictive Impact

SIMPLE SUMMARY: Forkhead box A1 protein (FOXA1) is described as a pioneer factor that binds to condensed chromatin, permitting the recruitment of other transcription factors to the DNA. Worthy of note, FOXA1 is an interacting partner of both the estrogen and androgen receptor, playing a crucial role in the development and progression of breast cancer. Moreover, it is necessary for the estrogen-receptor-binding and subsequent transcriptional activation of luminal genes in breast cancer cells. Herein, we review principal roles of FOXA1 in normal and neoplastic tissues, with special attention to its prognostic and predictive role in luminal and non-luminal breast cancers. ABSTRACT: The present review focuses on the function of the forkhead protein FOXA1 in breast cancer (BC) in relation to steroid hormone receptors. We explored the currently available analytic approaches for FOXA1 assessment both at gene and protein levels, comparing the differences between the available techniques used for its diagnostic assessment. In addition, we elaborated on data regarding the prognostic and predictive role of this marker in BC based on several studies that evaluated its expression in relation to the outcome and/or response to therapy. FOXA1, similar to the androgen receptor (AR), may have a dual role in BC according to hormonal status. In luminal cancers, its expression contributes to a better prognosis, while in triple-negative breast cancers (TNBC), it implies an adverse outcome. Consequently, we observed that FOXA1-positive expression in a neoadjuvant setting may predict a lack of response in luminal BC as opposed to TNBC, in which FOXA1 allegedly increases its chemosensitivity. In conclusion, considering its accessible and convenient identification by immunohistochemistry, its important impact on prognosis, and its suitability to identify patients with different responses to chemotherapy, we propose that FOXA1 could be tested in routine diagnostics as an additional prognostic and predictive marker in BC.