Management of Hormone-Responsive Postmenopausal Breast Cancer: Defining the Role of Anastrozole
Lynda R. Wiseman
Lesley J. Scott
Postmenopausal breast cancer is frequently hormone responsive and may be treated with agents that prevent estrogen activity. Tamoxifen is the most widely used of these agents, proving effective in both early and advanced disease. However, the role of tamoxifen has been challenged by the development of newer agents which have demonstrated at least equivalent activity and better tolerability, notably the nonsteroidal third-generation aromatase inhibitor anastrozole, which is currently the only other agent approved for primary adjuvant treatment of early disease and first-line treatment of advanced disease. In postmenopausal women with early breast cancer, anastrozole was associated with a significantly higher rate of disease-free survival (86.9% vs 84.5%) and a lower incidence of contralateral breast cancer than tamoxifen. Furthermore, the incidences of thromboembolic events and endometrial cancer were significantly lower with anastrozole. However, anastrozole was associated with an increase in musculoskeletal events (including fractures) and further evaluation of the clinical significance of this finding is warranted. Pharmacoeconomic analyses based on the results of this trial and conducted from different healthcare perspectives have all found anastrozole to be a cost-effective adjuvant therapy for early postmenopausal breast cancer. Clinical trial data indicate that switching patients who have already received 2 years' tamoxifen treatment to anastrozole reduces the risk of relapse and death compared with continuing treatment with tamoxifen. Further studies are warranted to determine the optimum sequence of agents and duration of adjuvant therapy. Large well designed trials have also shown first-line anastrozole therapy is at least as effective as tamoxifen in prolonging time to disease progression and overall survival in patients with advanced disease. Current data indicate that the drug is more effective than tamoxifen in patients whose tumors are known to express the estrogen receptor. Pharmacoeconomic analyses conducted from various healthcare perspectives support the use of anastrozole as a cost-effective treatment in this indication. Anastrozole has demonstrated similar efficacy to that of other approved agents, including letrozole and fulvestrant, as second-line therapy for patients who have failed first-line therapy (in most cases with tamoxifen). In conclusion, clinical and pharmacoeconomic data support the role of anastrozole as a primary adjuvant treatment for use across the entire spectrum of breast cancer encompassing early disease through to advanced metastatic disease, and reflect current treatment guidelines. Anastrozole has also proven effective in clinical trials in the neoadjuvant setting, though its use in this setting and in breast cancer prevention remains to be fully elucidated.
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