Impact of BMI on serum estradiol and bone turnover markers in postmenopausal women with hormone-sensitive early breast cancer treated with anastrozole

Abstract

Obesity increases the risk of all-cause and breast cancer mortality. As obese patients have higher levels of aromatase enzyme activity, conflicting results on the effect of body mass index (BMI) of a standard dose aromatase inhibitor on estradiol depletion have been reported. We prospectively investigated the effect of BMI on the efficacy of anastrozole in 70 postmenopausal women with early, ER-positive breast cancer to decrease serum estradiol assessed by a high-sensitive assay with a sensitivity limit of 5pg/ml over 24 months. Additionally, we examined the changes of bone markers expecting an inverse relationship. Overall, estradiol decreased from 12.6pg/ml (SD=5.4) to 4.0pg/ml (SD=5.6) over 24 months (p<0.001). In contrast, carboxy-terminal collagen crosslinks (CTX) and serum aminoterminal propeptide of type I collagen (PINP) increased from 0.26ng/ml (SD=0.18) to 0.40ng/ml (SD=0.24) and 41.5ng/ml (SD=19.7) to 59.1ng/ml (SD=29.1) (p<0.0001 for both). Baseline estradiol comprised significant differences comparing normal weight with overweight (p<0.01) or obese patients (p<0.001). After 12 and 24 months, overweight and obese patients showed a slightly, but insignificantly higher concentrations of estradiol compared to normal weight subjects. We found differences of CTX in comparison between normal weight and obese patients (0.33 vs. 0.21ng/ml; p<0.023) at baseline. At 12 and 24months, there was a significant BMI-independent increase in CTX. Estradiol concentrations in postmenopausal women with early, ER-positive breast cancer on anastrozole were significantly different in normal weight versus overweight or obese patients at baseline, but not at 12 and 24 months. CTX and PINP present a notable increase in the first 12months of anastrozole treatment, stabilizing thereafter.