Recent advances in the use of aromatase inhibitors for women postmenopausal breast cancer

Abstract

The aromatase enzyme catalyses the last step in estrogen biosynthesis. There are two classes of third-generation aromatase inhibitors: irreversible steroidal inhibitors (e.g. exemestane) and reversible non-steroidal inhibitors (e.g. anastrozole, letrozole). All three agents have been found to be equivalent or superior to megestrol acetate as second-line therapy for metastatic breast cancer. In the first-line setting, large phase III trials have shown that all three are equivalent or superior to tamoxifen in women with metastatic disease. Several large trials with varying study designs have been launched to analyse their role in the adjuvant setting. The four that have reported found longer average disease-free survival for women who received an aromatase inhibitor than for those who did not. In addition, one trial, MA.17, has shown a survival advantage associated with the use of an aromatase inhibitor in node-positive patients. Guidelines produced by the American Society of Clinical Oncology suggest that adjuvant therapy for postmenopausal women with hormone-receptor-positive breast cancer should include an aromatase inhibitor. However, the long-term consequences of estrogen deprivation in postmenopausal women remain uncertain, particularly with regard to bone and cardiovascular health. The advantages and disadvantages of different hormonal strategies should therefore be carefully considered in each individual case.