Effects of Exemestane, Anastrozole and Tamoxifen on Bone Mineral Density and Bone Turnover Markers in Postmenopausal Early Breast Cancer Patients: Results of N-SAS BC 04, the TEAM Japan Substudy

Abstract

Background: Use of aromatase inhibitors in women with postmenopausal breast cancer accompanies risks of bone loss. We evaluated changes in bone mineral density (BMD) and bone turnover markers in patients treated with exemestane, anastrozole or tamoxifen for hormone-sensitive postmenopausal early breast cancer. Patients and Methods: Sixty-eight patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational Japan bone substudy were randomly assigned to receive tamoxifen, exemestane or anastrozole. During a 2-year study period, lumbar spine BMD was measured using dual-energy X-ray absorptiometry, and urinary type I collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP) were also measured. Results: BMD at 2 years of treatment was higher in tamoxifen patients compared with exemestane and anastrozole patients; however, the intergroup difference was not significant (p = 0.2521 and p = 0.0753, respectively). BMD was higher in exemestane patients compared with anastrozole patients; however, the intergroup difference was not significant (p = 0.7059 and p = 0.8134, respectively). NTX and BAP were significantly lower in tamoxifen patients compared with exemestane and anastrozole patients at 1 and 2 years of treatment (p < 0.05). Conclusion: Tamoxifen may provide better bone protection compared with exemestane or anastrozole. The effect of exemestane and anastrozole on bone loss may be comparable in Japanese postmenopausal women.

Effect of adjuvant chemotherapy on carboxytelopeptide of cross-linked type I collagen of egyptian women with non-metastatic breast cancer

“…Chemotherapeutic aromatase inhibitors (e.g., exemestane and anastrozole) have been shown to directly inhibit osteoclast differentiation and bone resoption markers leading to osteoporosis in postmenopausal women with early BC [6], yet with apparently increased bone resorption biochemical markers, as also had been shown earlier [31,32]. It has been shown that osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts [4].…”

“…Consequently, total T-and Z-Scores after chemotherapy were also significantly (p<0.001) lower than those before chemotherapy, confirming that bone loss was directly related to treatment with adjuvant chemotherapy. In line with this, many studies reported that adjuvant chemotherapy may cause a rapid bone loss, increasing the risk of osteoporosis for pre-and postmenopausal women with BC later in life [1][2][3][4][5][6][7][24][25][26][27]. It has been shown that bone loss with aging occurs because hypogonadism may progress to primary osteoporosis.…”

“…Thus, women with BC are at increased risk for the development of osteoporosis and skeletal fractures, giving rise to significant morbidity and some mortality [3], as a consequence of aromatase inhibition or chemotherapyinduced ovarian failure [4,5]. Exemestane and anastrozole, two chemotherapeutic aromatase inhibitors, have been shown to directly inhibit osteoclast differentiation and bone resoption markers leading to osteoporosis in postmenopausal women with non-metastatic breast cancer (NMBC) [6]. The bone resorption cross-linked carboxytelopeptide of collagen type I (CTx-I) combined with BMD measurements, can be used for assessing bone health status in postmenopausal women [7,8].…”

Efficacy of zoledronic acid in postmenopausal Japanese women with early breast cancer receiving adjuvant letrozole: 12-month results

“…Okisiro et al [26] also showed that bone loss of Japanese women induced by anastrozole was less compared that of ATAC bone study (1.3 vs. 2.2% at 1 year and 2.8 vs. 4.0% at 2 years). In the Japanese subgroup bone study of TEAM, BMDs of patients treated with tamoxifen versus exemestane after 1 and 2 years were 88.1 and 87.8% versus 87.5 and 86.8%, although bone metabolic markers (urine NTx and BSAP) were significantly high in exemestane group compared with tamoxifen group [19]. In the phase III study, comparing tamoxifen for 5 years versus switch from tamoxifen for 1-4 years to anastrozole for 1-4 years in Japanese postmenopausal breast cancer patients (N-SAS BC03), fracture rate was not significantly different between two groups (tamoxifen 2.6%, tamoxifen to anastrozole 1.4%) [20].…”

“…In retrospective studies, Yoneda et al [18] reported no significant bone loss with 1-year treatment with anastrozole in Japanese women, and they speculated that Japanese women are less fat, and effects of aromatase inhibitors on bone mass might be less in lean women. In the Japanese subgroup study of TEAM (tamoxifen vs. exemestane), BMD of patients with tamoxifen and exemestane were not significantly different [19]. Furthermore, phase III study comparing tamoxifen versus switch from tamoxifen to anastrozole in Japanese postmenopausal breast cancer patients (N-SAS BC03) showed that fracture rate was not significantly different between two groups [20].…”