A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer

Fiona M. Mccaig (1) , Lorna Renshaw (1) , Linda Williams (2) , Oliver Young (1) , Juliette Murray (1) , Elizabeth J. Macaskill (1) , Mary Mchugh (1) , Rosemary Hannon (3) , J. Michael Dixon (1)

1 Breakthrough Research Unit, Edinburgh Breast Unit
2 Centre for Population Health Sciences, Medical School
3 Unit of Bone Metabolism, Metabolic Bone Centre

ALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg;  = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg;  = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen ( = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption.

Mots clés: ALIQUOT; Anastrozole; Bone markers; Breast cancer; Letrozole

Fiona M. Mccaig, Lorna Renshaw, Linda Williams, Oliver Young, Juliette Murray, et al.. A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer. Breast Cancer Research and Treatment, 2009, 119 (3), pp.643-651. ⟨10.1007/s10549-009-0646-0⟩. ⟨hal-00535417⟩