Endocrine Effects of Adjuvant Letrozole Compared With Tamoxifen in Hormone-Responsive Postmenopausal Patients With Early Breast Cancer: The HOBOE Trial

Abstract

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

Chemotherapy-induced ovarian toxicity in patients affected by endocrine-responsive early breast cancer

“…Tandem mass spectrometry, a validated method dosing steroids in the pg/ml range, may not be widely available [18]. Furthermore, tamoxifen has been reported to increase circulating estrogens and decrease FSH levels [110]. Increased levels of estradiol may result from cross-reactivity of tamoxifen and its metabolites in the estradiol assay.…”

Recognizing menopause in women with amenorrhea induced by cytotoxic chemotherapy for endocrine-responsive early breast cancer

“…Furthermore, tamoxifen has been reported to increase circulating estrogens and decrease FSH levels (Rossi et al 2009). AIs have been shown to profoundly decrease estrogens and increase FSH levels in postmenopausal patients (Rossi et al 2009). Increased levels of E 2 induced by tamoxifen may be related to cross-reactivity of tamoxifen and its metabolites in the E 2 assay (Rossi et al 2009).…”

“…Tandem mass spectrometry, a validated method used for dosing steroids in the picogram/milliliter range, is not widely available in nonresearch settings (Sundaram et al 2003, Smith et al 2006. Furthermore, tamoxifen has been reported to increase circulating estrogens and decrease FSH levels (Rossi et al 2009). AIs have been shown to profoundly decrease estrogens and increase FSH levels in postmenopausal patients (Rossi et al 2009).…”

“…However, how tamoxifen influences CIA/CIM remains unclear. It has been suggested that the drug increases plasma estradiol (E 2 ) levels and interferes with the hypothalamic-ovarian feedback loop that regulates estrogen synthesis (Rose & Davis 1980, Rossi et al 2009). …”

“…AIs have been shown to profoundly decrease estrogens and increase FSH levels in postmenopausal patients (Rossi et al 2009). Increased levels of E 2 induced by tamoxifen may be related to cross-reactivity of tamoxifen and its metabolites in the E 2 assay (Rossi et al 2009). Likewise, exemestane, a steroidal AI, may interfere with serum E 2 measurement (Johannessen et al 1997).…”