Estrogen-Receptor Antagonists as Second-Line Therapy in MBC
As many as 75% of advanced breast cancers in postmenopausal women are hormone sensitive, making these patients potentially good candidates for endocrine therapy. Indeed, there are several advantages to such an approach, including avoidance of troublesome side effects of chemotherapy. As breast cancer expert Dr. Stephen E. Jones has noted, "Endocrine therapy represents a safe and effective treatment modality in postmenopausal receptor positive patients, and is underutilized by oncologists" (personal communication).

Tamoxifen has long been a mainstay in the management of breast cancer, in both the adjuvant and metastatic settings. As front-line therapy in the metastatic setting, tamoxifen has been compared with the aromatase inhibitor drugs letrozole and anastrozole. These studies, which were conducted in both North America and worldwide, showed superiority of the aromatase inhibitors over tamoxifen with regard to time to progression (TTP). Thus, most breast cancer experts now feel that the aromatase inhibitors are the best choice in the front-line metastatic setting.

However, a significant proportion of patients continue to take tamoxifen, and because of its partial agonist activity, many will progress despite therapy. Because many of these tumors remain hormone sensitive, their disease lends itself to further endocrine manipulation. It is in this setting that the estrogen antagonist fulvestrant has been evaluated.