Bone turnover markers in postmenopausal breast cancer patients treated with fulvestrant
680 Background: Aromatase inhibitor (AI) therapy in patients with breast cancer accelerates bone turnover with increased secretion and excretion of bone turnover markers. Here, we report the effect of fulvestrant, an estrogen receptor (ER) antagonist with no agonist activity, on bone metabolism. Methods: 23 patients with either locally advanced primary [LAPC] or metastatic [MBC] disease who had clinical benefit (objective response/stable disease ≥6 months) during fulvestrant therapy were included in the study. Sequential tumor biopsies and blood samples were taken at baseline and after 3, 6, 9, 12 and 18 months of fulvestrant treatment (disease being stable throughout the study period). Serum was analyzed for bone formation markers (N-terminal propeptide of procollagen Type 1 [PINP] and bone-specific alkaline phosphatase [bone ALP]) and for the resorption marker C-terminal telopeptide (CTX). Data are presented as median percentage change (from baseline) in marker level with 95% confidence intervals (CI). Data were analyzed separately for patients with LAPC and MBC. Results: Changes in bone ALP (reference range: 3.9–46.8 ng/mL), PINP (20.6–82.1 ng/mL) and CTX (0.14–1.35 ng/mL) in patients with LAPC, are shown in the table . In a further 5 patients with LAPC who were already established on fulvestrant, there were no significant changes in markers over a 15-month period. No changes in markers were noted in the 4 patients with MBC. Conclusions: In this study, there was long-term stability of bone turnover markers in postmenopausal women with LAPC treated with fulvestrant over a period of 18 months. This property may be exploited in future with the use of fulvestrant earlier in the sequence of endocrine therapies particularly in the adjuvant setting and/or in patients with pre-existing decreased bone mass. [Table: see text] [Table: see text]