The aromatase inhibitor letrozole (Femarâ/ Femaraâ) and the aromatase inactivator exemestane (Aromasinâ) are currently widely used to treat estrogen receptor positive breast cancer in postmenopausal patients. Interestingly, exemestane may cause clinical disease stabilization following progression on non-steroidal AIs in patients with metastatic breast cancer indicating that additional effects, not necessarily related to estrogen-suppression, may be involved in the well-known “lack of cross-resistance”. The adipocytokine leptin has been shown to enhance the expression of aromatase via promoter II and I.3 using an AP-1 motif. In this study, we evaluated the serum levels of 12 adipokines relative to given treatment with aromatase inhibitors aiming for a direct head-to-head comparison between letrozole and exemestane in vivo.
The NEO-LET-EXE-trial is a neoadjuvant, randomized, open-label, intra-patient cross-over trial. Postmenopausal women with ER+, HER-2 negative, locally advanced breast cancer were enrolled. Blood specimens obtained at baseline, after 2 months and 4 months of treatment were available from 39 patients. All patients were randomized to sequential treatment starting with either letrozole (2.5 mg o.d.) or exemestane (25 mg o.d.) for 2 months followed by another 2 months on the alternative aromatase inhibitor. The serum levels of twelve adipokines were assessed using the Luminex xMAP technology (multiple ELISA).
Serum levels of leptin were significantly decreased during treatment with exemestane compared to treatment with letrozole (P < 0.001), regardless whether exemestane was given as first or second therapy. Furthermore, we observed a strong trend towards a reduction of serum levels of adiponectin during treatment with exemestane (P = 0.059). No significant changes in serum levels of the other adipocytokines were registered during treatment with aromatase inhibitors.
Our results suggest distinct influences of exemestane on serum leptin but also adiponectin levels that may contribute to the clinical well-document positive effects of exemestane following progression on non-steroidal AIs like letrozole.
Akershus University Hospital.
The South-Eastern Norway Regional Health Authority.
All authors have declared no conflicts of interest.