Kumar Anjali S, Benz Christopher C, Shim Veronica, Minami Christina A, Moore Dan H, Esserman Laura J
Department of Surgery, Kaiser Permanente Oakland Medical Center, Oakland, California, USA.
Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1028-33. doi: 10.1158/1055-9965.EPI-07-0726. Epub 2008 May 7.
Preclinical studies have shown the anticancer potential of HMG-CoA reductase enzyme inhibitors (statins), whereas epidemiologic studies remain controversial. Because lipophilic statins show preclinical anticancer activity against hormone receptor [estrogen receptor (ER)/progesterone receptor (PR)]-negative breast cancer models, we explored the hormone receptor phenotype of breast cancers that arise in statin users.
We did a retrospective cohort analysis via electronic pharmacy records from the Kaiser Permanente Northern California Cancer Registry on 2,141 female patients listed in 2003 as incident cases of breast malignancy. Measures included tumor grade, stage, and receptor phenotype in statin users versus nonusers and controlled for hormone replacement therapy and race.
387 of the 2,141 breast cancer patients used lipophilic statins [lovastatin (85%), simvastatin, and atorvastatin]. Fifty-one women developed ER/PR-negative tumors. The age-adjusted odds ratio (OR) of developing an ER/PR negative tumor was 0.63 (95% confidence interval, 0.43-0.92; P = 0.02) for statin use >or=1 year before breast cancer diagnosis compared with statin use <1 year (including nonuse). Breast cancers in patients with >or=1 year of statin use were more likely to be low grade (OR, 1.44) and less invasive stage (OR, 1.42).
Breast cancer patients with exposure to statins have proportionately fewer ER/PR-negative tumors that are of lower grade and stage. Although our data set cannot address whether statins affect the incidence of breast cancer, we show that statin use may influence the phenotype of tumors. This suggests a new potential strategy for breast cancer prevention, that of combining statins with agents that prevent ER-positive cancer (tamoxifen, aromatase inhibitors).
临床前研究已显示HMG-CoA还原酶抑制剂（他汀类药物）具有抗癌潜力，而流行病学研究仍存在争议。由于亲脂性他汀类药物在临床前对激素受体[雌激素受体（ER）/孕激素受体（PR）]阴性的乳腺癌模型具有抗癌活性，我们探究了使用他汀类药物患者所患乳腺癌的激素受体表型。
我们通过北加利福尼亚凯撒医疗中心癌症登记处的电子药房记录，对2003年登记为乳腺癌新发病例的2141名女性患者进行了回顾性队列分析。测量指标包括他汀类药物使用者与非使用者的肿瘤分级、分期和受体表型，并对激素替代疗法和种族进行了控制。
2141名乳腺癌患者中有387名使用亲脂性他汀类药物[洛伐他汀（85%）、辛伐他汀和阿托伐他汀]。51名女性患ER/PR阴性肿瘤。与乳腺癌诊断前使用他汀类药物<1年（包括未使用）相比，在乳腺癌诊断前使用他汀类药物≥1年的患者发生ER/PR阴性肿瘤的年龄调整优势比（OR）为0.63（95%置信区间，0.43 - 0.92；P = 0.02）。使用他汀类药物≥1年的患者的乳腺癌更可能为低分级（OR，1.44）和低侵袭分期（OR，1.42）。
接触他汀类药物的乳腺癌患者中，ER/PR阴性肿瘤的比例相对较少，且分级和分期较低。虽然我们的数据集无法确定他汀类药物是否影响乳腺癌的发病率，但我们表明使用他汀类药物可能会影响肿瘤的表型。这提示了一种新的乳腺癌预防潜在策略，即将他汀类药物与预防ER阳性癌症的药物（他莫昔芬、芳香化酶抑制剂）联合使用。
