Statins, commonly used to treat hypercholesterolemia, have also been proposed as anti-cancer agents. The identification of a predictive marker is essential. The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), which is inhibited by statins, might serve as such a marker. Thorough antibody validation was performed for four different HMGCR antibodies. Tumor expression of HMGCR (#AMAb90619, CL0260, Atlas Antibodies, Stockholm, Sweden) was evaluated in the Malmö Diet and Cancer Study breast cancer cohort. Statin use and cause of death data were retrieved from the Swedish Prescribed Drug Register and Swedish Death Registry, respectively. Breast cancer-specific mortality (BCM) according to statin use and HMGCR expression were analyzed using Cox regression models. Three-hundred-twelve of 910 breast cancer patients were prescribed statins; 74 patients before and 238 after their breast cancer diagnosis. HMGCR expression was assessable for 656 patients; 119 showed negative, 354 weak, and 184 moderate/strong expressions. HMGCR moderate/strong expression was associated with prognostically adverse tumor characteristics as higher histological grade, high Ki67, and ER negativity. HMGCR expression was not associated with BCM. Neither was statin use associated with BCM in our study. Among breast cancer patients on statins, no or weak HMGCR expression predicted favorable clinical outcome. These suggested associations need further testing in larger cohorts.

中文翻译：

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服用他汀类药物，HMGCR表达和乳腺癌生存率-马尔默饮食与癌症研究。

通常用于治疗高胆固醇血症的他汀类药物也已被提出作为抗癌药。预测标记的识别是必不可少的。他汀类药物所抑制的3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）可能是这样的标记。对四种不同的HMGCR抗体进行了彻底的抗体验证。在马尔默饮食与癌症研究乳腺癌队列中评估了HMGCR（＃AMAb90619，CL0260，Atlas Antibodies，Stockholm，Sweden）的肿瘤表达。他汀类药物的使用和死亡原因数据分别从瑞典处方药注册处和瑞典死亡登记处获取。使用他汀类药物和HMGCR表达的乳腺癌特异性死亡率（BCM）使用Cox回归模型进行了分析。910名乳腺癌患者中有三十二名接受了他汀类药物治疗；乳腺癌诊断之前和之后的238位患者中有74位患者。HMGCR表达可评估656例患者。119个显示否定，354个弱和184个中等/强表达。HMGCR中度/强表达与更高的组织学等级，较高的Ki67和ER阴性与预后不良的肿瘤特征相关。HMGCR表达与BCM不相关。在我们的研究中，他汀类药物与BCM均无关联。在使用他汀类药物的乳腺癌患者中，HMGCR表达没有或较弱预示了良好的临床结果。这些建议的协会需要在更大的队列中进一步测试。HMGCR中度/强表达与更高的组织学等级，较高的Ki67和ER阴性与预后不良的肿瘤特征相关。HMGCR表达与BCM不相关。在我们的研究中，他汀类药物与BCM均无关联。在使用他汀类药物的乳腺癌患者中，HMGCR表达没有或较弱预示了良好的临床结果。这些建议的协会需要在更大的队列中进一步测试。HMGCR中度/强表达与更高的组织学等级，较高的Ki67和ER阴性与预后不良的肿瘤特征相关。HMGCR表达与BCM不相关。在我们的研究中，他汀类药物与BCM均无关联。在使用他汀类药物的乳腺癌患者中，HMGCR表达没有或较弱预示了良好的临床结果。这些建议的协会需要在更大的队列中进一步测试。