Aromatase inhibitors and breast cancer

Abstract Breast cancer is the most prevalent cancer and the second leading cause of death among women worldwide. The advent of hormonal therapy has revolutionized the treatment for breast cancer for a century. In the 1960s, an important advance was the development of the antiestrogen tamoxifen. While this drug has had a major impact on breast cancer treatment, its partial agonist activity is associated with increased risk of stroke and endometrial cancer as well as drug resistance. One of the breakthroughs in breast cancer treatment is the discovery of aromatase inhibitors (AIs) in the early 1970s. AIs have proven to be effective in treating hormone receptor-positive breast cancer and lack the estrogenic effects of tamoxifen. They are now considered to be the standard treatment for postmenopausal women with hormone receptor-positive breast cancer. While AIs are effective in treating hormone receptor-positive breast cancer, resistance to AIs inevitably occurs in metastatic setting after prolonged suppression of estrogen production. This chapter summarizes the evolution of AIs, clinical efficacy of AIs, mechanisms of AI resistance, and the strategies to overcome resistance.