A study of the effects of the aromatase inhibitors anastrozole   and letrozole on bone metabolism in postmenopausal women   with estrogen receptor-positive breast cancer.
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.
McCaig
Fiona M
FM
Breakthrough Research Unit, Edinburgh Breast Unit, Western General Hospital, Edinburgh EH4 2XU, Scotland, UK.
Renshaw
Lorna
L
Williams
Linda
L
Young
Oliver
O
Murray
Juliette
J
Macaskill
Elizabeth J
EJ
McHugh
Mary
M
Hannon
Rosemary
R
Dixon
J Michael
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D001862:Bone Resorption / Q000139:chemically induced; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects*; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000096:biosynthesis; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects; D013629:Tamoxifen / Q000009:adverse effects; D014230:Triazoles / Q000009:adverse effects*
D047072:Aromatase Inhibitors; D009570:Nitriles; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D000077289:Letrozole