Targeting the estrogen receptor in clinical breast cancer.
Breast cancer is the most common cancer in women worldwide with more than 500,000 new cases diagnosed and 250,000 deaths annually. Treatment directed to inhibiting the action of the estrogen receptor (ER) represents one of the earliest examples of a successful targeted therapy for clinical breast cancer. We know that the ER functions as a transcription factor which controls estrogen-regulated genes important for the development, growth, and progression of breast cancer. The current, initial palliative treatment for women with estrogen-sensitive breast cancer is the antiestrogen tamoxifen. Patients whose tumors progress after responding to tamoxifen can achieve further responses from subsequent second-line therapy with agents such as the potent aromatase inhibitors, which have recently shown promise as potential first-line therapies. Our present understanding of the molecular mechanisms of action of ER, and its interaction downstream of various polypeptide growth factors and their receptors, cell survival conduits, and various protein kinase signaling pathways, has the potential to greatly increase our armory of hormonally-targeted strategies for the treatment and reversal of endocrine resistance. Therefore, combined directed therapies to these growth factor-triggered pathways, along with treatments directly targeting the ER, may provide more optimum treatment strategies in the future.
Fuqua
Suzanne A W
SA
Breast Center, Baylor College of Medicine, Houston, TX 77030, USA. sfuqua@breastcenter.tmc.edu
Cui
Yukun
Y