Selecting the optimal treatment for postmenopausal patients with hormone receptor-positive metastatic breast cancer remains a challenge. This decision was further complicated by a phase III trial conducted by SWOG that demonstrated an improvement in survival for the combination of anastrozole and fulvestrant. In this trial, anastrozole was administered at 1 mg daily alone or in combination with fulvestrant at 500 mg on day 1 and 250 mg thereafter.

Based on these results, Joyce A. O'Shaughnessy, MD, questions the efficacy of the 1 mg dose of anastrozole as a first-line treatment in this setting. Moreover, several questions remain unanswered regarding the optimal first-line treatment for these patients. Adding to the quandary, Sara Hurvitz, MD, points out that patients who received prior tamoxifen did not benefit as substantially from the combination.

Edith A. Perez, MD, believes the combination should not be a first-line choice. Instead, she believes the standard of care should be the 500 mg dose of fulvestrant alone. Andrew D. Seidman, MD, adds that men with ER-positive, tamoxifen refractory metastatic breast cancer also respond well to treatment with fulvestrant, further indicating that it should be a preferred first-line treatment. However, Hope S. Rugo, MD, suggests that many physicians administer aromatase inhibitors (AIs), such as anastrozole, in the first-line setting, since AIs are administered orally.

Based on the SWOG and other trials, O'Shaughnessy now preferentially administers the 500 mg dose of fulvestrant in the first-line setting for tamoxifen-naive patients. However, she notes, there are still questions about whether the SWOG results apply to other AIs, such as letrozole, which is being examined in combination with the novel CDK 4/6 inhibitor palbociclib. In general, Rugo notes, she would rather enroll patients to the clinical trial exploring palbociclib with letrozole, rather than selecting whether to use fulvestrant, anastrozole, or the combination.