Optimal sequence of hormonotherapy in advanced breast cancer

Several active, well tolerated hormonal agents have become available in recent years for the treatment of patients with advanced, hormone receptor-positive breast cancer. When used in an appropriate sequential strategy, hormonal therapies offer the opportunity of prolonging disease control and maintaining quality of life. The widening use of aromatase inhibitors in the adjuvant setting, however, means that traditional sequential cascades must be revised. The review describes the most relevant evidence that can contribute to the optimal positioning of each agent in the sequence.

Most recent phase II and III trials of hormonal therapy in advanced breast cancer have examined the role of exemestane, letrozole, anastrozole, and fulvestrant in postmenopausal women.

Partial non-cross resistance between nonsteroidal (letrozole and anastrozole) and steroidal (exemestane) aromatase inhibitors may allow treatment with exemestane after a nonsteroidal aromatase inhibitor and vice versa. The estrogen receptor downregulator fulvestrant is also an option after treatment with aromatase inhibitors. The role of the progestin megestrol acetate and, paradoxically, of tamoxifen in the sequential strategy for advanced breast cancer is less well studied.