Update on fulvestrant for hormone receptor-positive advanced breast cancer

Hormone therapy delays the need for cytotoxic chemotherapy and provides palliation in postmenopausal women with hormone receptor-positive advanced breast cancer. With multiple hormone therapy options available, it is important to define how and when each agent should be used. Each blocks estrogen-mediated breast cancer growth - tamoxifen by blocking estrogen-receptor (ER) activity, the third-generation aromatase inhibitors (Als) by blocking adrenal estrogen synthesis, and fulvestrant by causing selective ER downregulation. Whereas tamoxifen is a partial estrogen agonist, fulvestrant is devoid of estrogen agonist activity. In multicenter phase III studies, fulvestrant was at least as effective as the Al anastrozole in women whose disease progressed on other hormone therapies (primarily tamoxifen). Fulvestrant also showed similar efficacy to tamoxifen in the first-line treatment of advanced breast cancer and, in smaller studies, was effective following the failure of both tamoxifen and Als to control the disease. Fulvestrant was well tolerated in these studies, producing less arthralgia than anastrozole and fewer estrogenic effects than tamoxifen. These studies indicate that fulvestrant is an important treatment option for advanced breast cancer. Ongoing clinical studies are exploring the optimal position for fulvestrant within the endocrine treatment sequence and whether combinations with other endocrine therapy or with novel targeted agents having different mechanisms of action will provide even greater clinical benefit.