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

Abstract

International audienceALIQUOT (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

AI-related BMD variation in actual practice conditions: A prospective cohort study

“…However, the current analysis is in accordance with some studies, indicating that prior tamoxifen treatment profoundly increases the effects of AIs on bone turnover, resulting in a greater decrease in BMD (McCaig et al 2010). A possible explanation for this phenomenon is the rebound effect; unfortunately, the positive influence of tamoxifen not only ceases when tamoxifen therapy is finished (McCaig et al 2010) but also causes a marked bone loss when switching to AI. Moreover, tamoxifen is a standard treatment for perimenopausal women, but not for postmenopausal women.…”

“…There is compelling evidence for its beneficial effects, from reducing bone resorption and stimulating bone formation in postmenopausal breast cancer patients (Resch et al 1998). However, the current analysis is in accordance with some studies, indicating that prior tamoxifen treatment profoundly increases the effects of AIs on bone turnover, resulting in a greater decrease in BMD (McCaig et al 2010). A possible explanation for this phenomenon is the rebound effect; unfortunately, the positive influence of tamoxifen not only ceases when tamoxifen therapy is finished (McCaig et al 2010) but also causes a marked bone loss when switching to AI.…”

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07)

“…The interruption of tamoxifen combined with the rapid fall in estrogen levels induced by the AI may promote an accelerated loss of BMD following the switch [7,23,24]. McCaig et al [25] reported that stopping tamoxifen and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naive patients. The measurement of bone turnover biomarkers also showed that the effect of AIs occurs relatively rapidly after initiation of the treatment [9,24,[26][27][28][29].…”

A Retrospective Study on Screening and Management of Osteoporosis in Breast Cancer Women Treated With Aromatase Inhibitors in Libya

“…They have shown themselves to be superior to the previous tamoxifen in terms of the efficacy, safety and tolerability profile (5). One side effect of these three compounds, however, is a decrease in bone mineral density (BMD) and an increased risk of fracture (6)(7)(8)(9)(10). In fact, by blocking the conversion of androgens to estrogens in peripheral tissue, they have proven to suppress plasma and tissue estrogen level by > 98% in vivo.…”