Effects of adjuvant exemestane versus anastrozole on bone mineral density for women with early breast cancer (MA.27B): a companion analysis of a randomised controlled trial

Abstract

Summary Background Treatment of breast cancer with aromatase inhibitors is associated with damage to bones. NCIC CTG MA.27 was an open-label, phase 3, randomised controlled trial in which women with breast cancer were assigned to one of two adjuvant oral aromatase inhibitors—exemestane or anastrozole. We postulated that exemestane—a mildly androgenic steroid—might have a less detrimental effect on bone than non-steroidal anastrozole. In this companion study to MA.27, we compared changes in bone mineral density (BMD) in the lumbar spine and total hip between patients treated with exemestane and patients treated with anastrozole. Methods In MA.27, postmenopausal women with early stage hormone (oestrogen) receptor-positive invasive breast cancer were randomly assigned to exemestane 25 mg versus anastrozole 1 mg, daily. MA.27B recruited two groups of women from MA.27: those with BMD T-scores of –2·0 or more (up to 2 SDs below sex-matched, young adult mean) and those with at least one T-score (hip or spine) less than –2·0. Both groups received vitamin D and calcium; those with baseline T-scores of less than –2·0 also received bisphosphonates. The primary endpoints were percent change of BMD at 2 years in lumbar spine and total hip for both groups. We analysed patients according to which aromatase inhibitor and T-score groups they were allocated to but BMD assessments ceased if patients deviated from protocol. This study is registered with ClinicalTrials.gov, NCT00354302. Findings Between April 24, 2006, and May 30, 2008, 300 patients with baseline T-scores of –2·0 or more were accrued (147 allocated exemestane, 153 anastrozole); and 197 patients with baseline T-scores of less than –2·0 (101 exemestane, 96 anastrozole). For patients with T-scores greater than –2·0 at baseline, mean change of bone mineral density in the spine at 2 years did not differ significantly between patients taking exemestane and patients taking anastrozole (−0·92%, 95% CI −2·35 to 0·50 vs −2·39%, 95% CI −3·77 to –1·01; p=0·08). Respective mean loss in the hip was −1·93% (95% CI −2·93 to –0·93) versus −2·71% (95% CI −4·32 to –1·11; p=0·10). Likewise for those who started with T-scores of less than –2·0, mean change of spine bone mineral density at 2 years did not differ significantly between the exemestane and anastrozole treatment groups (2·11%, 95% CI −0·84 to 5·06 vs 3·72%, 95% CI 1·54 to 5·89; p=0·26), nor did hip bone mineral density (2·09%, 95% CI −1·45 to 5·63 vs 0·0%, 95% CI −3·67 to 3·66; p=0·28). Patients with baseline T-score of –2·0 or more taking exemestane had two fragility fractures and two other fractures, those taking anastrozole had three fragility fractures and five other fractures. For patients who had baseline T-scores of less than –2·0 taking exemestane, one had a fragility fracture and four had other fractures, whereas those taking anastrozole had five fragility fractures and one other fracture. Interpretation Our results demonstrate that adjuvant treatment with aromatase inhibitors can be considered for breast canc...

Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy

“…Failure to find any associations in exemestane-treated women in the SNP analysis may have been due to a small sample size being underpowered to detect modest pharmacogenetic effects. Alternatively, non-steroidal versus steroidal AIs have been shown to have different pharmacodynamic effects, and our results may indeed suggest different biological effects (15, 23–25). …”

Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover

“…The open label Phase III randomized clinical trial MA.27 bone subprotocol (MA.27B), in which exemestane and anastrozole were directly compared, failed to demonstrate a statistically significant difference in spine or hip BMD at 2 years, although there were suggestions that exemestane may have mild bone sparing effects based on differences in rates of osteoporosis diagnosis and new prescription of bisphosphonate medication between the two groups [11, 12]. It is of-note that MA.27B was originally planned for longer follow-up but was truncated when the parent study MA.27 closed [11]. Hence, further exploration of the differential bone effects of steroidal and non-steroidal AI remains clinically relevant [11, 12].…”

Adjuvant Endocrine Therapy and Bone Health in Breast Cancer

“…However, this finding is not definitive and the rate of fragility fractures was similar in both arms at 4 % [62]. The bone substudy of the comparison study of anastrozole versus exemestane did not demonstrate a statistically significant difference between skeletal outcomes [60].…”

“…The TEAM trial compared exemestane with tamoxifen and reported a significant decline in BMD at the lumbar spine and hip in the exemestane group [59]. Due to exemestane being a mildly androgenic steroid, it was thought possibly protective on bone compared to other AI's; although, the recent study by Goss et al did not show a difference in BMD when it was compared with anastrozole [60]. In the bone substudy of the phase III trial comparing letrozole to tamoxifen, letrozole was associated with a significant decline in BMD compared to tamoxifen alone [61•].…”