Hormone receptor positive (HR+) breast cancer represents the most common subtype of breast cancer. Metastatic HR+ breast cancer may develop resistance to standard hormone therapies, arising from genomic alterations in the estrogen receptor and/or upregulation of other signal transduction pathways. Areas covered: In this review, we discuss hormone resistance and strategies to overcome it, from the pre-clinical and clinical perspectives. This review includes a discussion of inhibition of the PI3K/AKT/mTOR, CDK 4/6, histone deacetylation, fibroblast growth factor receptor, and immune pathways, based on review of relevant literature. Expert commentary: Several emerging novel therapies to improve the response to hormone therapy are approved or are in development. The most promising agents at present are inhibitors of CDK 4/6 and mTOR, which have already been incorporated into treatment in the advanced stage setting and are under study for early stage disease.
Keywords: CDK 4/6 inhibitors; PI3K/AKT/mTOR inhibitors; fibroblast growth factor receptor inhibitors; histone deacetylation inhibitors; hormone receptor positive breast cancer; hormone resistance.