Effect of Bisphosphonate Use on Risk of Postmenopausal Breast Cancer Results From the Randomized Clinical Trials of Alendronate and Zoledronic Acid
Effect of Bisphosphonate Use on Risk of Postmenopausal Breast Cancer Results From the Randomized Clinical Trials of Alendronate and Zoledronic Acid
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DOI：
10.1001/jamainternmed.2014.3634
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发表时间：
2014-10-01
影响因子：
39
通讯作者：
Black, Dennis M.
中科院分区：
文献类型：
--
作者：
Hue, Trisha F.;Cummings, Steven R.;Black, Dennis M.
重要性 研究表明，双膦酸盐可能具有抗肿瘤和抗转移特性。最近，观察性研究表明双磷酸盐可能对乳腺癌有保护作用，但尚未在随机试验中测试双磷酸盐的使用对乳腺癌风险的影响。 目的 使用 2 项随机 (1:1)、双盲、安慰剂对照试验的数据评估绝经后乳腺癌发病率与双磷酸盐使用的关系。 设计、设置和参与者 骨折干预试验 (FIT) 随机分配6459 名 55 至 81 岁的女性接受阿仑膦酸钠或安慰剂治疗，平均随访时间为 3.8 年。唑来膦酸每年一次的健康成果和降低发病率关键性骨折试验 (HORIZON-PFT) 将 7765 名 65 至 89 岁的女性随机分配到每年静脉注射唑来膦酸或安慰剂组，平均随访时间为 2.8 年。数据收集于美国（FIT 和 HORIZON-PFT）以及亚太地区、欧洲、北美和南美（HORIZON-PFT）的临床中心。在这两项研究中，患有复发性乳腺癌或报告有乳腺癌病史的女性均被排除在分析之外。在每项试验中，都对每份癌症不良事件报告进行了盲审，以核实发生的浸润性乳腺癌病例。主要分析使用对数秩检验比较活性药物组与安慰剂组的事件。 干预 阿仑膦酸钠与安慰剂 (FIT) 或唑来膦酸与安慰剂 (HORIZON-PFT)。 主要结果和测量 双磷酸盐治疗组与安慰剂组相比，发生乳腺癌的风险比。 结果 FIT 中乳腺癌发生率没有显着差异：1.5%（n = 46）安慰剂组为 1.8%(n = 57)，阿仑膦酸钠组为 1.8%（风险比 [HR]，1.24 [95% CI，0.84-1.83]）。在 HORIZON-PFT 中，也没有显着差异：安慰剂组为 0.8%(n = 29)，唑来膦酸组为 0.9%(n = 33)（HR，1.15 [95% CI，0.70-1.89]）。将 FIT 和 HORIZON-PFT 的数据合并后也没有显着差异（HR，1.20 [95% CI，0.89-1.63]）。 结论和相关性 这 2 项随机临床试验并不支持观察性研究的结果。与观察性研究的结果相反，我们发现 3 至 4 年的双膦酸盐治疗并没有降低侵袭性绝经后乳腺癌的风险。
IMPORTANCE Studies have shown that bisphosphonates may have antitumor and antimetastatic properties. Recently, observational studies have suggested a possible protective effect of bisphosphonates on breast cancer, but the effect of bisphosphonate use on risk of breast cancer has not been tested in randomized trials.OBJECTIVE To assess the relationship of postmenopausal breast cancer incidence and bisphosphonate use using data from 2 randomized (1:1), double-blind, placebo-controlled trials.DESIGN, SETTING, AND PARTICIPANTS The Fracture Intervention Trial (FIT) randomly assigned 6459 women aged 55 to 81 years to alendronate or placebo for a mean follow-up of 3.8 years. The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7765 women aged 65 to 89 years to annual intravenous zoledronic acid or placebo for a mean follow-up of 2.8 years. Data were collected at clinical centers in the United States (FIT and HORIZON-PFT) and in Asia and the Pacific, Europe, North America, and South America (HORIZON-PFT). Women, in either study, with recurrent breast cancer or who reported a history of breast cancer were excluded from analyses. In each trial, a blinded review was conducted of each cancer adverse event report to verify incident invasive breast cancer cases. The primary analysis compared events in the active vs placebo group using a log-rank test.INTERVENTION Alendronate vs placebo (FIT) or zoledronic acid vs placebo (HORIZON-PFT).MAIN OUTCOMES AND MEASURES Hazard ratio for incident breast cancer in the bisphosphonate treatment group compared to the placebo group.RESULTS There was no significant difference in the rate of breast cancer in FIT: 1.5%(n = 46) in the placebo group and 1.8%(n = 57) in the alendronate group (hazard ratio [HR], 1.24 [95% CI, 0.84-1.83]). In HORIZON-PFT, there was also no significant difference: 0.8%(n = 29) in the placebo group and 0.9%(n = 33) in the zoledronic acid group (HR, 1.15 [95% CI, 0.70-1.89]). There was also no significant difference when the data from FIT and HORIZON-PFT were pooled (HR, 1.20 [95% CI, 0.89-1.63]).CONCLUSIONS AND RELEVANCE These 2 randomized clinical trials do not support the findings from observational research. Contrary to the results from observational studies, we found that 3 to 4 years of bisphosphonate treatment did not decrease the risk of invasive postmenopausal breast cancer.