Jiralerspong Sao, Palla Shana L, Giordano Sharon H, Meric-Bernstam Funda, Liedtke Cornelia, Barnett Chad M, Hsu Limin, Hung Mien-Chie, Hortobagyi Gabriel N, Gonzalez-Angulo Ana M
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, 77030-4009, USA.
J Clin Oncol. 2009 Jul 10;27(20):3297-302. doi: 10.1200/JCO.2009.19.6410. Epub 2009 Jun 1.
Population 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.
We 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.
The 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.
Diabetic 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.
人群研究表明,糖尿病患者使用二甲双胍可降低癌症发病率和死亡率。二甲双胍在体外可抑制癌细胞生长,在体内可抑制肿瘤生长。然而,几乎没有临床数据支持这一点。我们的目的是确定在接受新辅助化疗的糖尿病乳腺癌患者中,使用二甲双胍是否与病理完全缓解(pCR)率的变化相关。
我们确定了1990年至2007年间接受早期乳腺癌新辅助化疗的2529例患者。将患者分为三组进行比较:68例服用二甲双胍的糖尿病患者、87例未服用二甲双胍的糖尿病患者和2374例非糖尿病患者。使用独立性卡方检验比较三组之间的pCR率,并使用比例二项式检验进行两两比较。使用多变量逻辑回归模型评估预测pCR的因素。
二甲双胍组的pCR率为24%,非二甲双胍组为8.0%,非糖尿病组为16%(P = 0.02)。二甲双胍组与非二甲双胍组(P = 0.007)以及非二甲双胍组与非糖尿病组(P = 0.04)的两两比较具有显著性。二甲双胍组与非糖尿病组之间的pCR率比较有趋势但未达到显著性(P = 0.10)。在调整糖尿病、体重指数、年龄、分期、分级、受体状态和新辅助紫杉烷使用情况后,使用二甲双胍可独立预测pCR(优势比,2.95;P = 0.04)。
接受二甲双胍和新辅助化疗的糖尿病乳腺癌患者的pCR率高于未接受二甲双胍的糖尿病患者。有必要进行更多研究以评估二甲双胍作为抗肿瘤药物的潜力。