Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study
Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study
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DOI：
10.1200/jco.2016.70.3116
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发表时间：
2017-04-10
影响因子：
45.3
通讯作者：
Thurlimann, Beat
中科院分区：
文献类型：
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作者：
Borgquist, Signe;Giobbie-Hurder, Anita;Thurlimann, Beat
降胆固醇药物（CLM）在预防乳腺癌复发中的作用已被报道。CLM可以通过降低雌激素胆固醇代谢物27-羟基胆固醇的水平来减弱通过雌激素受体的信号传导。内分泌治疗对胆固醇水平和高胆固醇血症本身的影响可能会抵消芳香化酶抑制剂的预期效果。患者和MethodsThe乳腺国际集团（BIG）进行了一项随机，第三阶段，双盲试验，BIG 1-98，其中包括8,010绝经后妇女与早期，激素受体阳性浸润性乳腺癌从1998年至2003年。在进入研究时和每6个月直至5.5年测量全身总胆固醇水平和CLM的使用。累积发生率函数用于描述在存在竞争风险的情况下启动CLM。边际结构考克斯比例风险模型研究了内分泌治疗期间开始CLM与结局之间的关系。三个时间到事件的终点被认为是：无病生存，乳腺癌的无间隔，和远端复发的无interval. Results胆固醇水平降低在他莫昔芬治疗。在内分泌治疗期间开始CLM的789例患者中，大多数来自来曲唑单药治疗组（n = 318），其次是序贯他莫昔芬-来曲唑（n = 189）、来曲唑-他莫昔芬（n = 176）和他莫昔芬单药治疗（n = 106）。内分泌治疗期间启动CLM与改善无病生存期相关（风险比[HR]，0.79; 95% CI，0.66 - 0.95; P = 0.01），无乳腺癌间期（HR，0.76; 95% CI，0.60至0.97; P = 0.02），和远端无复发间期（HR，0.74; 95% CI，0.56 - 0.97;结论在激素受体阳性的早期乳腺癌患者中，辅助内分泌治疗期间使用降胆固醇药物可能在预防乳腺癌复发方面发挥作用。乳腺癌分期我们建议在前瞻性随机试验中对这些观察结果进行说明。(C)2017年美国临床肿瘤学会
PurposeCholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors.Patients and MethodsThe Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor-positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free survival, breast cancer-free interval, and distant recurrence-free interval.ResultsCholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer-free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence-free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03).ConclusionCholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor-positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials. (C) 2017 by American Society of Clinical Oncology