Fundacion Instituto Valenciano de Oncologia, Valencia, Spain.
Clin Breast Cancer. 2012 Feb;12(1):40-8. doi: 10.1016/j.clbc.2011.08.002. Epub 2011 Oct 19.
Letrozole is a proven and effective adjuvant therapy in postmenopausal women with hormone receptor-positive (HR(+)) early breast cancer (EBC). As with other aromatase inhibitors (AIs), long-term letrozole administration is associated with decreased bone mineral density (BMD) and increased fracture risk. This study compared potential bone-protecting effects of immediate vs. delayed administration of zoledronic acid (ZOL) in patients with EBC receiving adjuvant letrozole.
Patients with HR(+) EBC in whom adjuvant letrozole treatment was initiated (2.5 mg/day for 5 years) were randomized to immediate ZOL treatment (immediate ZOL) or delayed ZOL treatment (delayed ZOL) (both at 4 mg every 6 months). Patients in the delayed ZOL group received ZOL only for a BMD T-score that decreased to < -2.0 (lumbar spine [LS] or total hip [TH]) or for fracture. The primary endpoint was percentage change in the LS BMD at month 12. Patients were stratified by established or recent postmenopausal status, baseline T-scores, and adjuvant chemotherapy history.
At 12 months, the LS BMD increased in the immediate ZOL group (+2.72%) but decreased in the delayed ZOL group (-2.71%); the absolute difference between groups was significant (5.43%; P < .0001). Across all subgroups, patients receiving immediate ZOL had significantly increased LS and TH BMD vs. those who received delayed ZOL (P < .0001). Differences in fracture incidence or disease recurrence could not be ascertained because of early data cutoff and low incidence of events. Adverse events were generally mild, transient, and consistent with the known safety profiles of both agents.
Immediate ZOL administration effectively prevented BMD loss and increased BMD in postmenopausal women with HR(+) EBC receiving adjuvant letrozole, regardless of BMD status at baseline.
来曲唑是一种已被证实且有效的绝经后激素受体阳性（HR(+））早期乳腺癌（EBC）辅助治疗药物。与其他芳香化酶抑制剂（AIs）一样，长期来曲唑治疗会导致骨密度（BMD）降低和骨折风险增加。本研究比较了在接受辅助来曲唑治疗的 EBC 患者中，立即给予唑来膦酸（ZOL）与延迟给予 ZOL 的潜在骨保护作用。
起始接受辅助来曲唑治疗（每天 2.5mg，持续 5 年）的 HR(+)EBC 患者被随机分为立即 ZOL 治疗组（立即 ZOL）或延迟 ZOL 治疗组（延迟 ZOL）（均为每 6 个月 4mg）。延迟 ZOL 组仅在 BMD T 评分降至< -2.0（腰椎 [LS]或全髋 [TH]）或发生骨折时给予 ZOL。主要终点为第 12 个月时 LS 骨密度的变化百分比。患者按已绝经或近期绝经状态、基线 T 评分和辅助化疗史进行分层。
在 12 个月时，立即 ZOL 组的 LS 骨密度增加（+2.72%），而延迟 ZOL 组的 LS 骨密度下降（-2.71%）；两组间的绝对差异有统计学意义（5.43%；P<.0001）。在所有亚组中，与接受延迟 ZOL 的患者相比，接受立即 ZOL 的患者 LS 和 TH 骨密度均显著增加（P<.0001）。由于数据提前截止和事件发生率低，无法确定骨折发生率或疾病复发的差异。不良事件通常为轻度、短暂，与两种药物的已知安全性特征一致。
在接受辅助来曲唑治疗的 HR(+)EBC 绝经后妇女中，立即给予 ZOL 可有效防止 BMD 丢失并增加 BMD，无论基线时的 BMD 状态如何。
