Hormone Receptor Positive Early Breast Cancer: What Role for Aromatase Inhibitors?

Abstract: Breast cancer is a significant problem worldwide. Five years of Tamoxifen has been the established endocrine adjuvant therapy for both pre- and post-menopausal women for several decades, until the more recent introduction of AI’s for use in post-meno-pausal ER-positive EBC. There are three third generation AI’s currently available commercially these include non steroidal (anastrozole and letrozole) and steroidal inhibitors (exemestane). Anastrozole, letrozole and exemestane have all been compared against tamoxifen in randomised phase III studies as upfront monotherapy and all show a significant improvement in disease free survival (DFS). However there has been no overall survival (OS) benefit seen with AI’s in any of the upfront trials. The question of upfront AI versus switch is complicated and is highly debated. Evidence from randomised phase III trials shows an improvement in DFS for all three AI’s in the switch setting. The only trial to show a significant survival benefit is the IES trial where patients were switched to exemestane. More data is required to directly compare the AI’s in the upfront setting and study the most appropriate duration of the AI’s. There does still appear to be a role for tamoxifen in low risk patients and for intermediate risk patients when used in combination with aromatase inhibitors in the switch setting