Hormone-Biological Therapy in Breast Cancer: Preclinical Evidence, Clinical Studies and Future Directions

Background: The development of resistance to endocrine agents is a major issue in the treatment of ER-positive breast cancer patients. Evidence of cross-talk among signaling pathways and recent advances in understanding biology of this neoplasm have led to the new concept of hormone-biological therapy. Aims: The main aim of this review was to comprehensively examine ongoing and concluded clinical trials about endocrine agents used in combination with biological drugs. The second aim was to provide up-to-date knowledge of preclinical studies in this flourishing field, considering several in vitro and in vivo models, by focusing on the main signaling pathways involved in breast tumorigenesis. Materials and Methods: We performed a literature search for papers published in MEDLINE database until January 2009. We selected the most significant data presented as abstract or poster during the relevant international meetings for breast cancer (ASCO, ESMO and San Antonio Breast Cancer Symposium). Moreover, we systematically reviewed a publicly available registry of federally and privately supported clinical trials conducted in the United States and around the world to provide updated information about concluded trials and ongoing trials not yet published. Results/Conclusion: Hormone-biological therapy is a relatively new option in the treatment of breast cancer with and some combinations seemingly effective in certain settings. Numerous trials are ongoing and they will help to better clarify the role of different combined therapies. In parallel, cancer biology has a central role in providing a deeper understanding of this heterogeneous disease where preclinical studies will be necessary to test new compounds and strategies.