Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer
Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer
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DOI：
10.1200/jco.2009.19.6410
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发表时间：
2009-07-10
影响因子：
45.3
通讯作者：
Gonzalez-Angulo, Ana M.
中科院分区：
文献类型：
--
作者：
Jiralerspong, Sao;Palla, Shana L.;Gonzalez-Angulo, Ana M.
目的人群研究表明二甲双胍用于糖尿病患者可降低癌症发病率和死亡率。二甲双胍在体外抑制癌细胞生长，在体内抑制肿瘤生长。然而，几乎没有临床数据支持这一点。我们的目的是确定二甲双胍的使用是否与接受新辅助化疗的糖尿病乳腺癌患者的病理完全缓解（pCR）率的变化相关。Patients and MethodsWe确定了1990年至2007年期间接受新辅助化疗的早期乳腺癌患者2,529例。患者按组进行比较：68名服用二甲双胍的糖尿病患者，87名未服用二甲双胍的糖尿病患者和2，374名非糖尿病患者。使用卡方检验比较三组之间的pCR率，并使用二项式比例检验进行成对比较。预测pCR的因素进行了评估，使用多变量logistic回归model.ResultsThe率的pCR是24%的二甲双胍组，8.0%的非二甲双胍组，16%的非糖尿病组（P = .02）。二甲双胍组和非二甲双胍组（P = .007）以及非二甲双胍组和非糖尿病组（P = .04）之间的配对比较具有显著性。二甲双胍组和非糖尿病组之间pCR率的比较趋向于但未达到显著性（P = 0.10）。调整糖尿病、体重指数、年龄、分期、分级、受体状态和新辅助紫杉烷使用后，二甲双胍的使用是pCR的独立预测因素（优势比，2.95; P = .04）。结论接受二甲双胍和新辅助化疗的乳腺癌糖尿病患者的pCR率高于未接受二甲双胍的糖尿病患者。需要进行额外的研究来评估二甲双胍作为抗肿瘤药物的潜力。
PurposePopulation studies have suggested that metformin use in diabetic patients decreases cancer incidence and mortality. Metformin inhibits the growth of cancer cells in vitro and tumors in vivo. However, there is little clinical data to support this. Our purpose was to determine whether metformin use was associated with a change in pathologic complete response (pCR) rates in diabetic patients with breast cancer receiving neoadjuvant chemotherapy.Patients and MethodsWe identified 2,529 patients who received neoadjuvant chemotherapy for early-stage breast cancer between 1990 and 2007. Patients were compared by groups: 68 diabetic patients taking metformin, 87 diabetic patients not taking metformin, and 2,374 nondiabetic patients. pCR rates were compared between the three groups using chi(2) tests of independence and compared pair-wise using a binomial test of proportions. Factors predictive of pCR were assessed using a multivariate logistic regression model.ResultsThe rate of pCR was 24% in the metformin group, 8.0% in the nonmetformin group, and 16% in the nondiabetic group (P = .02). Pairwise comparisons between the metformin and nonmetformin groups (P = .007) and the nonmetformin and nondiabetic groups (P = .04) were significant. Comparison of the pCR rates between the metformin and nondiabetic groups trended toward but did not meet significance (P = .10). Metformin use was independently predictive of pCR ( odds ratio, 2.95; P = .04) after adjustment for diabetes, body mass index, age, stage, grade, receptor status, and neoadjuvant taxane use.ConclusionDiabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pCR rate than do diabetics not receiving metformin. Additional studies to evaluate the potential of metformin as an antitumor agent are warranted.