Clinical trial

Breast Cancer Research and Treatment

, Volume 119, Issue 3, pp 643-651

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. McCaigAffiliated withBreakthrough Research Unit, Edinburgh Breast Unit, Western General Hospital
  • , Lorna RenshawAffiliated withBreakthrough Research Unit, Edinburgh Breast Unit, Western General Hospital
  • , Linda WilliamsAffiliated withCentre for Population Health Sciences, Medical School, University of Edinburgh
  • , Oliver YoungAffiliated withBreakthrough Research Unit, Edinburgh Breast Unit, Western General Hospital
  • , Juliette MurrayAffiliated withBreakthrough Research Unit, Edinburgh Breast Unit, Western General Hospital
  • , Elizabeth J. MacaskillAffiliated withBreakthrough Research Unit, Edinburgh Breast Unit, Western General Hospital
  • , Mary McHughAffiliated withBreakthrough Research Unit, Edinburgh Breast Unit, Western General Hospital
  • , Rosemary HannonAffiliated withUnit of Bone Metabolism, Metabolic Bone Centre, Northern General Hospital
  • , J. Michael DixonAffiliated withBreakthrough Research Unit, Edinburgh Breast Unit, Western General Hospital Email author 

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Abstract

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; n = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; n = 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 (n = 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.

Keywords

ALIQUOT Anastrozole Bone markers Breast cancer Letrozole