Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
J Clin Oncol. 2012 Aug 10;30(23):2844-52. doi: 10.1200/JCO.2011.39.7505. Epub 2012 Jun 11.
Emerging evidence suggests that metformin may reduce breast cancer incidence, but reports are mixed and few provide information on tumor characteristics. Therefore, we assessed associations among diabetes, metformin use, and breast cancer in postmenopausal women participating in Women's Health Initiative clinical trials.
In all, 68,019 postmenopausal women, including 3,401 with diabetes at study entry, were observed over a mean of 11.8 years with 3,273 invasive breast cancers diagnosed. Diabetes incidence status was collected throughout follow-up, with medication information collected at baseline and years 1, 3, 6, and 9. Breast cancers were confirmed by review of central medical records and pathology reports. Cox proportional hazards regression, adjusted for breast cancer risk factors, compared breast cancer incidence in women with diabetes who were metformin users or nonusers with breast cancer incidence in women without diabetes.
Compared with that in women without diabetes, breast cancer incidence in women with diabetes differed by diabetes medication type (P = .04). Women with diabetes receiving medications other than metformin had a slightly higher incidence of breast cancer (hazard ratio [HR], 1.16; 95% CI, 0.93 to 1.45), and women with diabetes who were given metformin had lower breast cancer incidence (HR, 0.75; 95% CI, 0.57 to 0.99). The association was observed for cancers positive for both estrogen receptor and progesterone receptor and those that were negative for human epidermal growth factor receptor 2.
Metformin use in postmenopausal women with diabetes was associated with lower incidence of invasive breast cancer. These results can inform future studies evaluating metformin use in breast cancer management and prevention.
新出现的证据表明,二甲双胍可能降低乳腺癌的发病率,但报告结果不一,且很少有报告提供肿瘤特征方面的信息。因此,我们评估了参加妇女健康倡议临床试验的绝经后妇女中糖尿病、二甲双胍使用与乳腺癌之间的关联。
共有 68019 名绝经后妇女参与了研究,其中 3401 名妇女在研究入组时患有糖尿病,平均随访 11.8 年,诊断出 3273 例浸润性乳腺癌。在整个随访期间收集糖尿病发病情况,在基线和第 1、3、6 和 9 年收集药物信息。通过对中心病历和病理报告的审查来确认乳腺癌。采用 Cox 比例风险回归,根据乳腺癌风险因素进行调整,比较了患有糖尿病且使用二甲双胍或未使用二甲双胍的妇女与无糖尿病的妇女的乳腺癌发病率。
与无糖尿病的妇女相比,患有糖尿病的妇女的乳腺癌发病率因糖尿病药物类型而异(P =.04)。服用二甲双胍以外药物的糖尿病妇女的乳腺癌发病率略高(风险比 [HR],1.16;95%CI,0.93 至 1.45),而服用二甲双胍的糖尿病妇女的乳腺癌发病率较低(HR,0.75;95%CI,0.57 至 0.99)。该关联在雌激素受体和孕激素受体阳性的癌症和人表皮生长因子受体 2 阴性的癌症中均观察到。
在患有糖尿病的绝经后妇女中使用二甲双胍与浸润性乳腺癌的发病率较低相关。这些结果可以为评估二甲双胍在乳腺癌管理和预防中的使用的未来研究提供信息。