Rational Management of Endocrine Resistance in Breast Cancer A Comprehensive Review of Estrogen Receptor Biology, Treatment Options, and Future Directions

Endocrine therapy for breast cancer was introduced more than 100 years ago. In the last 30 years, it has been demonstrated that tamoxifen significantly improves outcomes for patients with hormone-responsive breast tumors. Aromatase inhibitors, Which suppress the production of estrogen, are recognized today as all effective alternative for estrogen-receptor-positive breast cancer in postmenopausal women. However, despite ail initial response to treatment, many tumors eventually recur or progress. When selecting subsequent endocrine therapy, it is helpful to Understand the mechanisms of hormone resistance, consider the goals of treatment, and evaluate the clinical potential of each available drug. The objective of this article was to review the Underlying mechanisms of action and resistance for each type of hormone therapy, evaluate the most recent data regarding the Use of endocrine agents after disease progression or recurrence, and explore potential combinations of hormone therapies with novel molecules that target key growth factor signaling pathways. Cancer 2008;113:2385-97. (C) 2008 American Cancer Society.