Luminal B型乳腺癌合并糖尿病患者临床病理特征及预后分析

Clinicopathologic characteristics and prognostic analysis of luminal B breast cancer patients with diabetes

目的：探讨luminal B型乳腺癌合并糖尿病患者临床病理特征及预后特点。方法：选取天津医科大学肿瘤医院2002年1月至2006年12月收治的luminal B型乳腺癌4401例，其中合并糖尿病乳腺癌479例及未合并糖尿病乳腺癌3392例。按照高敏感性luminal B和Her-2阳性luminal B两种亚型分组进行对比研究。各亚型进一步分组为二甲双胍治疗组、非二甲双胍治疗组和非糖尿病组。研究指标包括乳腺癌死亡率、临床病理分期、淋巴结状况、化疗方案及内分泌治疗方案。Kaplan-Meier方法分析各分组之间死亡率是否存在差异。Cox比例风险模型用于检测与预后相关的独立因素。结果：Kaplan-Meier单因素分析法显示高敏感性luminal B、Her-2阳性luminal B型中二甲双胍治疗组、非二甲双胍治疗组和非糖尿病组癌症死亡率均存在显著性差异，5年生存率依次为93.5%、81.0%、89.0%（P〈0.001）和84.0%、77.0%、83.0%（P=0.035）。Cox回归模型多因素分析显示两类分型中相对于二甲双胍治疗组，非二甲双胍治疗组预后较差（P〈0.001，P=0.044）。但仅高敏感性luminal B分型相对于二甲双胍治疗组，非糖尿病组预后较差（P=0.038）。临床特征方面，二甲双胍治疗组和非二甲双胍治疗组T3～4期患者比例高（P〈0.001），更易发生淋巴结转移（P=0.001）。结论：luminal B型乳腺癌分型中以二甲双胍治疗组作为参考，非二甲双胍治疗组均预示较差的预后，其中仅高敏感性luminal B分型中非糖尿病组预示了较差的预后。糖尿病用药对不同的luminal B分型乳腺癌患者预后影响可能不同。

Objective：To investigate the clinical, pathological, and prognostic characteristics of luminal B breast cancer patients with diabetes. Methods：A total of 479 luminal B breast cancer patients with diabetes and 3 392 luminal B breast cancer patients without diabetes who were treated between January 2002 and December 2006 were enrolled in this study. The luminal B breast cancer patients were further divided into the luminal B （high ki67） and luminal B （Her-2/neu＋） subgroups. Each subgroup was further grouped into metformin-treated, non-metformin-treated, and non-diabetic groups. The indicators included cancer-specific mortality, clinical, pathological stage, lymph node status, chemotherapy, and endocrine therapy. The survival analysis of each group was performed using the Kaplan-Meier method, and the significance was determined using the logrank test. Cox proportional hazard model was used to examine the correlation between each factor and the prognosis. Results：The Kaplan-Meier analysis results revealed that the breast cancer mortality rates in the metformin-treated, non-metformin-treated, and non-diabetic groups were significantly different in both luminal B （high ki67） and luminal B （Her-2/neu＋） subgroups （logrank test：P〈0.001, P=0.035）, and the respective five-year survival rates were 93.5%, 81%, and 89%for the luminal B （high ki67） subgroup and 84%, 77%, and 83%for the luminal B （Her-2/neu＋） subgroup. The Cox multifactorial regression analysis results showed that compared with the metformin-treated group, the non-metformin-treated group was associated with a significantly increased risk of mortality （P〈0.001, P=0.044） in the two subgroups. Meanwhile, the non-diabetic group was associated with an increased risk of mortality （P=0.038） in the luminal B （high ki67） subgroup only. The percentage of elderly （P〈0.001）, menopausal （P〈0.001）, obese （P〈0.001）, and＆nbsp;patients with cardio-cerebrovascular complications （P〈0.001） tended to be higher in the metformin-treated and non-metformin-treated groups than in the diabetic group. Moreover, the metformin-and non-metformin-treated groups in the luminal B （high ki67） subgroup were associated with high percentages of T3/4 pathological stage （P〈0.001）, lymph node metastasis （P=0.001）. The non-metformin-treated group was associated with a lower percentage of invasive ductal carcinoma （P=0.001） compared with the other two groups. Conclusion：The non-metformin-treated group resulted in worse clinical outcomes in both subgroups compared with the metformin-treated group. Meanwhile, the non-diabetic group resulted in the worst prognosis among the three groups in the luminal B （high ki67） subgroup. These findings suggest that the choice of different anti-diabetic drugs may influence the prognosis of luminal B breast cancer patients with diabetes.