The potency and clinical efficacy of aromatase inhibitors across the breast cancer continuum

Abstract

The strategy of using estrogen suppression to treat breast cancer led to the development of aromatase inhibitors, including the third-generation nonsteroidal compounds anastrozole and letrozole, and the steroidal compound exemestane. Aromatase inhibitors potently inhibit aromatase activity and also suppress estrogen levels in plasma and tissue. In clinical studies in postmenopausal women with breast cancer, third-generation aromatase inhibitors were shown superior to tamoxifen for the treatment of metastatic disease. Studies of adjuvant therapy with aromatase inhibitors include (i) head-to-head studies of 5 years of the aromatase inhibitor versus 5 years of tamoxifen monotherapy; (ii) sequential therapy of 2-3 years of tamoxifen followed by an aromatase inhibitor (or the opposite sequence) versus 5 years of tamoxifen monotherapy; (iii) extended therapy with an aromatase inhibitor after 5 years of tamoxifen; and (iv) sequential therapy with an aromatase inhibitor versus aromatase inhibitor monotherapy. Recent results from the Arimidex, Tamoxifen, Alone or in Combination and Breast International Group 1-98 trials advocate using an aromatase inhibitor upfront. This article examines the clinical data with aromatase inhibitors, following a brief summary of their pharmacology.

Figure 1.

Design of adjuvant aromatase inhibitor trials. ABCSG, Austrian Breast and Colorectal Cancer Study Group; AG, aminoglutethimide; ANA, anastrozole; ARNO, Arimidex–Nolvadex; ATAC, Arimidex, Tamoxifen, Alone or in Combination; EXE, exemestane; IES, Intergroup Exemestane Study; ITA, Italian Tamoxifen Anastrozole; LET, letrozole; NSABP, National Surgical Adjuvant Breast and Bowel Project; R, randomization; TAM, tamoxifen; TEAM, Tamoxifen, Exemestane Adjuvant Multicenter.

Figure 2.

Cumulative incidence of breast cancer recurrence in the sequential treatment analysis of the Breast International Group 1–98 trial at a median 71 months of follow-up. A: T - L versus L, B; L - T versus L. Reprinted with permission [78]. Copyright© 2009 Massachusetts Medical Society.