Hines Stephanie L, Mincey Betty, Dentchev Todor, Sloan Jeff A, Perez Edith A, Johnson David B, Schaefer Paul L, Alberts Steve, Liu Heshan, Kahanic Stephen, Mazurczak Miroslaw A, Nikcevich Daniel A, Loprinzi Charles L
Mayo Clinic Jacksonville, Jacksonville, FL 32224, USA.
Breast Cancer Res Treat. 2009 Oct;117(3):603-9. doi: 10.1007/s10549-009-0332-2. Epub 2009 Feb 12.
Postmenopausal women with breast cancer (BC) are at increased risk for bone loss. Bisphosphonates improve bone mineral density (BMD) in normal postmenopausal women. The purpose of this study was to determine if immediate treatment with zoledronic acid preserves BMD in postmenopausal women with BC starting letrozole after tamoxifen. Postmenopausal women with BC completing tamoxifen were treated with daily letrozole 2.5 mg/vitamin D 400 I.U., calcium 500 mg twice daily and were randomized to upfront or delayed zoledronic acid 4 mg every 6 months. Patients in the delayed arm were only given zoledronic acid if they developed a post-baseline BMD T score <-2.0 or had a fracture. The primary endpoint was the mean percent change in lumbar spine (LS) BMD at 1 year. About 558 women enrolled; 395 provided 1 year BMD data. The upfront arm experienced a mean change of +3.66% in LS BMD versus -1.66% for the delayed group (P < 0.001). Changes at the femoral neck/total hip were also greater for the upfront versus delayed arms (P < 0.001; P < 0.001) with differences persisting at 2 years. Patients in the delayed arm were more likely to experience a clinically meaningful 5% loss of BMD at all sites versus the upfront zoledronate group. Patients in the upfront arm were slightly more likely to report limb edema, fatigue, fever, nausea and jaw osteonecrosis(1%). Upfront zoledronic acid prevents bone loss in postmenopausal women with BC starting letrozole after tamoxifen.
绝经后乳腺癌（BC）患者骨质流失风险增加。双膦酸盐可提高正常绝经后女性的骨矿物质密度（BMD）。本研究的目的是确定唑来膦酸立即治疗能否在他莫昔芬治疗后开始来曲唑治疗的绝经后BC女性中保留骨密度。完成他莫昔芬治疗的绝经后BC女性每日服用2.5mg来曲唑/400国际单位维生素D，每日两次服用500mg钙，并随机分为每6个月一次的 upfront 或延迟使用4mg唑来膦酸组。延迟组的患者只有在基线后骨密度T评分<-2.0或发生骨折时才给予唑来膦酸。主要终点是1年时腰椎（LS）骨密度的平均百分比变化。约558名女性入组；395名提供了1年骨密度数据。upfront组LS骨密度平均变化为+3.66%，而延迟组为-1.66%（P<0.001）。upfront组与延迟组相比，股骨颈/全髋部的变化也更大（P<0.001；P<0.001），且在2年时差异持续存在。与 upfront 唑来膦酸组相比，延迟组患者在所有部位更有可能经历具有临床意义的骨密度5%的损失。upfront组患者报告肢体水肿、疲劳、发热、恶心和颌骨坏死（1%）的可能性略高。upfront使用唑来膦酸可预防他莫昔芬治疗后开始来曲唑治疗的绝经后BC女性的骨质流失。
