Abstract 24P
Background
This study is, to the best of our knowledge, the only direct head-to-head comparison of letrozole and exemestane concerning suppression of serum estrogen levels in postmenopausal breast cancer patients.
Methods
In this cross-over design study, 102 breast cancer patients were randomized into two cohorts for neoadjuvant endocrine therapy. Cohort 1 initially received letrozole (2.5 mg daily) for 3 months, then switched to exemestane (25 mg daily) for another 3 months. Cohort 2, conversely, started with exemestane and then switched to letrozole. Serum levels of estrone, estradiol, letrozole, and exemestane were measured using an ultrasensitive LC-MS/MS assay. This enabled precise monitoring of drug efficacy, and provided invaluable quality control for drug adherence, a known challenge in endocrine therapy, ensuring accurate assessment of the therapeutic comparison.
Results
Letrozole achieved superior suppression of serum estrogen levels compared to exemestane. In Cohort 1, which started with letrozole, estrone and estradiol levels significantly decreased from baseline to 0.2 pmol/L and 0.4 pmol/L, respectively, but increased after switching to exemestane. Conversely, in Cohort 2, which began with exemestane, letrozole further reduced estrogen levels upon cross-over. Notably, while on letrozole, 94% of patients had estrone levels below the quantification limit, compared to only 35% when on exemestane. Serum drug levels confirmed treatment adherence and were correlated with the degree of estrogen suppression.
Conclusions
This study conclusively demonstrates letrozole's superior efficacy in suppressing serum estrogens compared to exemestane during neoadjuvant breast cancer treatment. The findings indicate that the well-documented lack of cross-resistance between these drugs in clinical settings, allowing sequential therapy in MBC, is likely due to mechanisms beyond estrogen suppression. Our research group is currently investigating several additional, hithero unknown anti-tumor effects during exemestane therapy. In the long run, our results may improve the selection of individual patients to the different types of aromatase inhibitors.
Legal entity responsible for the study
Akershus University Hospital, Norway.
Funding
Has not received any funding.
Disclosure
J. Geisler: Financial Interests, Institutional, Advisory Board: Novartis. All other authors have declared no conflicts of interest.