Adjuvant hormonal therapy for postmenopausal women

Approximately 75% of all breast cancer is hormone receptor positive and the majority arises in postmenopausal women. In the United States alone, there are over 100,000 women annually who are diagnosed with postmenopausal hormone-receptor-positive disease. Adjuvant hormonal therapy substantially decreases a woman's risk of developing recurrent breast cancer and improves overall mortality. For almost two decades, a 5-year course of tamoxifen was the standard treatment offered to almost all women with hormone-receptor-positive disease. Over the past decade, the aromatase inhibitors have emerged as highly effective agents in the treatment of hormone-receptor-positive breast cancer. Multiple large trials including 25,000 women have assessed the role of the aromatase inhibitors in the adjuvant setting. These studies have demonstrated that the use of an aromatase inhibitor, either in place of tamoxifen or following a 2-year to 5-year course of tamoxifen, will reduce the risk of disease recurrence compared with the use of a 5-year course of tamoxifen alone. To date, these studies have not demonstrated a substantial improvement in overall survival, but the follow-up was relatively short. The optimal treatment approach has not been identified. Recently completed and ongoing trials are comparing a 5-year course of an aromatase inhibitor with the use of sequential therapy. Given the natural history of hormone-receptor-positive breast cancer, there is also great interest in treatment strategies that extend beyond 5 years. The toxicity profile of the aromatase inhibitors differs from tamoxifen, and these differences need to be considered in making clinical decisions. Ultimately, it is probable that different treatment approaches will be appropriate for different women based on tumor biology, pharmacogenetic variability, and susceptibility to side effects.