Dr. O'Regan on Breast Cancer Endocrine Therapy Resistance

Ruth M. O’Regan, MD, director of Translational Breast Cancer Research, professor, hematology and oncology, medical oncology, Winship Cancer Institute, Emory University, discusses resistance to endocrine therapy in patients with metastatic, hormone receptor-positive breast cancer.

The optimal treatment for patients with this type of disease is endocrine therapy, O’Regan says, but unfortunately all cancers will eventually develop resistance to endocrine therapy. The mechanisms that cause this resistance are complex, but researchers have learned that increased signaling through growth-factor receptor pathways, PI3K pathway, and MAPK pathways have important roles in endocrine resistance.

O’Regan says physicians believe the activation of these growth-factor receptors sets off a phosphorylation cascade. The cascade affects the estrogen receptor, causing it to no longer be a viable target for endocrine therapy.

However, there are many agents that target various parts of these pathways, including VEGF, HER2, EGFR, and insulin growth factor receptor-1. However, O’Regan says inhibition of mTOR has shown to be one of the most important pathways in reversing patients’ resistance to endocrine therapy.