ABSTRACT
Introduction: 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.
Declaration of interest
HS Rugo receives research support provided to the Regents of the University of California from Pfizer, Novartis, Lilly and Genentech/Roche. They have also received travel support from Puma and Mylan for presentations. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. A reviewer on this manuscript has disclosed that they have acted as a consultant for Novartis, Pfizer, and Lilly. Another reviewer on this manuscript has disclosed that they have received honoraria, research grants and travel support from Novartis, Pfizer, Lilly, Roche, Celgene, Amgen, Bristol-Myers Squibb, Puma Biotechnology, and Daiichi-Sankyo. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose