Management of Advanced Breast Cancer: Defining the Role of Anastrozole
Gillian M. Keating
Karen L. Goa
Breast cancer is the most common malignancy affecting women and imposes a substantial economic burden on society. Estrogen is thought to play a major role in both the initiation and promotion of hormone dependent breast cancer, and a number of well recognized risk factors for breast cancer reflect increased cumulative estrogen exposure (e.g. early menarche, late menopause). Metastatic breast cancer is an incurable condition and the goals of treatment are to relieve symptoms, improve health-related quality of life and prolong life. Women with hormone receptor-positive disease are candidates for hormonal treatment. In contrast, chemotherapy is traditionally the treatment of choice in those with hormone receptor-negative disease or symptomatic visceral disease. Anastrozole is a highly selective nonsteroidal type II aromatase inhibitor that suppresses plasma and intratumoral estrogen levels. The results of 2 multicenter, randomized, double-blind trials have shown anastrozole to be at least as effective as tamoxifen in the first-line treatment of postmenopausal women with advanced breast cancer, although survival data are lacking. In the smaller of these trials, the median time to disease progression was significantly prolonged (p = 0.005) in anastrozole, compared with tamoxifen, recipients (11.1 vs 5.6 months), although combined analysis of the 2 trials revealed no significant difference between anastrozole and tamoxifen in terms of this end-point. Similarly, anastrozole has been shown to be at least as effective as megestrol in the second-line treatment of postmenopausal women with advanced breast cancer in 2 multicenter randomized studies. Combined analysis of the studies revealed a significant survival advantage (p < 0.025) for anastrozole 1 mg/day, compared with megestrol 40mg 4 times daily, recipients (estimated hazard ratio 0.78; 97.5% confidence interval 0.6 to <1). Tolerability is an important consideration in women with advanced breast cancer. The most common adverse events associated with anastrozole therapy were gastrointestinal disturbance, hot flushes, asthenia and pain. Anastrozole is associated with less vaginal bleeding and thromboembolic disease than tamoxifen and less bodyweight gain than megestrol. Anastrozole also appears to be a cost-effective option in the first- and second-line treatment of advanced breast cancer, although data are limited. Conclusion: Current treatment guidelines support the use of anastrozole in the second-line treatment of postmenopausal women with advanced breast cancer. Although current treatment guidelines do not yet reflect this, data from recent, well designed studies demonstrate that anastrozole is likely to be a viable alternative to tamoxifen in the first-line treatment of postmenopausal women with advanced breast cancer.
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