Endocrine Effects of Tamoxifen Plus Exemestane in Postmenopausal Women with Breast Cancer

Abstract

Purpose: In some specific circumstances, combined hormonal therapies for breast cancer seem to be more effective than single maneuvers. In two laboratory mammary cancer models, the combination of the aromatase inactivator exemestane plus tamoxifen gives a higher response rate than is found with either agent alone.To evaluate the endocrine effects of the combination of exemestane and tamoxifen, we studied 33 postmenopausal women disease-free following primary treatments for breast cancer who were taking tamoxifen for at least 3 months.Design: After observation for symptoms on tamoxifen for 4 weeks, blood samples were taken and patients were begun additionally on exemestane 25 mg p.o. qd. Eight weeks later, blood samples were again taken, and exemestane was discontinued.Results: A decrease in alkaline phosphatase was found with exemestane treatment (P = 0.06), whereas no change in osteocalcin level was observed. A decrease in high-density lipoprotein cholesterol level was found (P = 0.0025), whereas total cholesterol, low-density lipoprotein cholesterol and triglyceride levels showed no changes with exemestane treatment. Estradiol, estrone, and estrone sulfate levels decreased to immeasurable or very low levels with exemestane treatment (all P < 0.001). No significant changes in frequencies of common drug-associated side effects, such as vasomotor symptoms or weight change, were found.Conclusions: Based on the absence of adverse endocrine effects with the addition of exemestane to tamoxifen therapy observed in this study, further clinical evaluation of the efficacy of this combination is warranted.

Differential profile of letrozole and exemestane on bone turnover markers in vinylcyclohexene diepoxide treated ovotoxic female mice

“…Because exemestane also reduced ALP in the femoral epiphysis, it is discernible that it may impair bone formation in femoral epiphysis while having no effect on bone resorption. Thus, there seems to be a differential profile of the two aromatase inhibitors on bone biomarkers which is also in agreement with some previous reports [6,45]. However, our results differ from the study by McCloskey and co-workers (2007) which reported all three aromatase inhibitors viz.…”

Effect of Exemestane on Tamoxifen Pharmacokinetics in Postmenopausal Women Treated for Breast Cancer

“…A portion of the plasma aliquots from the week 4 and week 12 blood samples was separated and assayed for estrone, estrone sulfate, and estradiol concentrations, as well as for osteocalcin, total and HDL cholesterol, triglycerides, and alkaline phosphatase. The results of the enzyme, lipid, and bone resorption assays are reported elsewhere (25). After the collection of blood samples at week 12, the subjects discontinued the exemestane and left the study on tamoxifen.…”

Molecular signatures of neoadjuvant endocrine therapy for breast cancer: characteristics of response or intrinsic resistance

“…However, in two preclinical models using human xenograft tumors in rodents [7,8] the steroidal AI exemestane, which irreversibly inhibits the aromatase enzyme, was shown to be more effective when combined with tamoxifen than either agent alone. In addition, two pilot clinical trials suggested that co-administration of tamoxifen does not affect exemestane pharmacokinetics or pharmacodynamics and that the combination is well tolerated and active [9][10][11].…”