Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ann Oncol. 2012 Jul;23(7):1771-80. doi: 10.1093/annonc/mdr534. Epub 2011 Nov 22.
Insulin/insulin-like growth factor-I (IGF-I) signaling is a mechanism mediating the promoting effect of type 2 diabetes (DM2) on cancer. Human epidermal growth factor receptor (HER2), insulin receptor and IGF-I receptor involve the same PI3K/AKT/mTOR signaling, and different antidiabetic pharmacotherapy may differentially affect this pathway, leading to different prognoses of HER2+ breast cancer.
We reviewed 1983 consecutive patients with HER2+ breast cancer treated between 1 January 1998 and 30 September 2010. The overall survival, breast cancer-specific death rate, age, race, nuclear grade, stage, menopausal status, estrogen and progesterone receptor status, body mass index and classes of antidiabetic pharmacotherapy were analyzed.
A Cox regression analysis showed that DM2 [P=0.026, hazard ratio (HR)=1.42, 95 % confidence interval (95 % CI) 1.04-1.94] predicted poor survival of stage≥2 HER2+ breast cancer. In Kaplan-Meier analysis, metformin predicted lengthened survival and so did thiazolidinediones. Analyzing only the diabetics, Cox regression showed that metformin (P=0.041, HR=0.52, 95 % CI 0.28-0.97) and thiazolidinediones (P=0.036; HR=0.41, 95% CI 0.18-0.93) predicted lengthened survival, and competing risk analysis showed that metformin and thiazolidinediones were associated with decreased breast cancer-specific mortality (P=0.023, HR=0.47, 95% CI 0.24-0.90 and P=0.044, HR=0.42, 95 % CI 0.18-0.98, respectively).
Thiazolidinediones and metformin users are associated with better clinical outcomes than nonusers in diabetics with stage≥2 HER2+ breast cancer. The choice of antidiabetic pharmacotherapy may influence prognosis of this group.
胰岛素/胰岛素样生长因子-I（IGF-I）信号是介导 2 型糖尿病（DM2）促进癌症发生的机制之一。人表皮生长因子受体（HER2）、胰岛素受体和 IGF-I 受体涉及相同的 PI3K/AKT/mTOR 信号通路，不同的抗糖尿病药物治疗可能会对该通路产生不同的影响，从而导致 HER2+乳腺癌的预后不同。
我们回顾了 1983 例连续接受 HER2+乳腺癌治疗的患者，治疗时间为 1998 年 1 月 1 日至 2010 年 9 月 30 日。分析了总生存期、乳腺癌特异性死亡率、年龄、种族、核分级、分期、绝经状态、雌激素和孕激素受体状态、体重指数和抗糖尿病药物治疗类别。
Cox 回归分析显示，DM2 [P=0.026，风险比（HR）=1.42，95 %置信区间（95 % CI）1.04-1.94]预测 stage≥2 HER2+乳腺癌的生存不良。在 Kaplan-Meier 分析中，二甲双胍预测生存延长，噻唑烷二酮类药物也是如此。仅分析糖尿病患者，Cox 回归显示二甲双胍（P=0.041，HR=0.52，95 % CI 0.28-0.97）和噻唑烷二酮类药物（P=0.036；HR=0.41，95 % CI 0.18-0.93）预测生存延长，竞争风险分析显示二甲双胍和噻唑烷二酮类药物与降低乳腺癌特异性死亡率相关（P=0.023，HR=0.47，95 % CI 0.24-0.90 和 P=0.044，HR=0.42，95 % CI 0.18-0.98）。
与非使用者相比，噻唑烷二酮类药物和二甲双胍使用者在 stage≥2 HER2+乳腺癌的糖尿病患者中具有更好的临床结局。抗糖尿病药物治疗的选择可能会影响这一组患者的预后。
