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腔面型乳腺癌糖尿病女性患者的临床病理特征及预后分析

Clinical pathological characteristics and prognostic analysis of diabetic women with luminal subtype breast cancer.

作者信息

Xiao Yuanting, Zhang Sheng, Hou Guofang, Zhang Xiaobei, Hao Xiaomeng, Zhang Jin

机构信息

Surgical Department, Tianhe Hospital, Tianjin, China.

出版信息

Tumour Biol. 2014 Mar;35(3):2035-45. doi: 10.1007/s13277-013-1270-5. Epub 2013 Oct 5.

Abstract

This study selected luminal-type breast cancer patients as the study subjects. The patients were divided into groups according to the presence of diabetes and the types of medication used, and the patients' clinicopathological characteristics and prognostic indicators were explored. A total of 5,785 patients with luminal-type breast cancer admitted to Tianjin Medical University Cancer Institute and Hospital between January 2002 and December 2006 were selected as the study subjects. The subjects included 680 breast cancer patients with diabetes and 5,105 breast cancer patients without diabetes. The patients were divided into Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes. Each subtype was further divided into a metformin group, a non-metformin group, and a nondiabetic group. The research indicators included breast cancer mortality, age, body mass index (BMI), amenorrhea, the presence of cardiovascular and cerebrovascular disease, pathological stage, pathological type, lymph node involvement, vessel carcinoma embolus, and the chemotherapy and endocrine regimen. A Kaplan-Meier analysis was conducted to analyze the differences in breast cancer mortality rates among the groups. The Cox proportional hazard model was adopted to detect independent factors related to prognosis. Kaplan-Meier univariate analysis showed that for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes, the cancer-specific mortality rates differed significantly among the metformin, non-metformin, and nondiabetic groups. The 5-year survival rates were 94%, 82%, and 91% (P = 0.002); 93.5%, 81%, and 89% (P < 0.001); and 84%, 77%, and 83% (P = 0.035) for the subtypes within each group, respectively. Cox regression multivariate analysis showed that compared with the metformin group, all three subtypes of the, the non-metformin group showed poorer prognosis (hazard ratio [HR], 3.579; 95% confidence interval [CI], 1.506-8.506 [P = 0.004]; HR, 3.232; 95% CI, 1.839-5.678 [P < 0.001]; HR, 2.034; 95% CI,1.019-4.059 [P = 0.044] for Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+, respectively). Compared with the metformin group, the diabetic group showed poorer prognosis only for the Luminal B (high ki67) subtype (HR, 1.762; 95% CI, 1.033-3.005 [P = 0.038]). In addition, for the Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subgroups, there was a higher proportion of elderly patients (P < 0.001) and postmenopausal patients (P < 0.001) in the metformin and non-metformin groups than in the nondiabetic group. Moreover, the probability of having cardiovascular and cerebrovascular disease was also higher (P < 0.001) in the metformin and non-metformin groups. For the Luminal B (high ki67) and Luminal B (her-2/neu +) subgroups, there was a higher proportion of obese patients in the metformin and non-metformin groups (P < 0.001). In terms of clinical characteristics, for the Luminal B (high ki67) subtype, the proportion of patients with invasive ductal carcinoma was lower in the non-metformin group than in the other two groups (P = 0.001). In both the metformin and non-metformin groups, the proportion of T3/4 patients was higher (P < 0.001), the proportion of patients with lymph node metastasis was higher (P = 0.001), and the proportion of patients with vessel carcinoma embolus was higher (P = 0.001) compared with the nondiabetic group. In conclusion, compared with the metformin group, the non-metformin group had a poorer prognosis for all subtypes of luminal breast cancer. In the diabetic group, only patients with the Luminal B (high ki67) subtype exhibited a poorer prognosis. Therefore, different diabetes medication may have a different impact on the prognosis of different subtypes of luminal breast cancer.

摘要

本研究选取腔面型乳腺癌患者作为研究对象。根据糖尿病的有无及所用药物类型将患者分组,探讨患者的临床病理特征及预后指标。选取2002年1月至2006年12月在天津医科大学肿瘤医院收治的5785例腔面型乳腺癌患者作为研究对象。研究对象包括680例糖尿病乳腺癌患者和5105例非糖尿病乳腺癌患者。将患者分为腔面A型、腔面B型(高ki67)和腔面B型(her-2/neu+)亚型。每个亚型再进一步分为二甲双胍组、非二甲双胍组和非糖尿病组。研究指标包括乳腺癌死亡率、年龄、体重指数(BMI)、闭经情况、心血管和脑血管疾病的存在情况、病理分期、病理类型、淋巴结受累情况、血管癌栓以及化疗和内分泌治疗方案。采用Kaplan-Meier分析方法分析各组乳腺癌死亡率的差异。采用Cox比例风险模型检测与预后相关的独立因素。Kaplan-Meier单因素分析显示,对于腔面A型、腔面B型(高ki67)和腔面B型(her-2/neu+)亚型,二甲双胍组、非二甲双胍组和非糖尿病组的癌症特异性死亡率差异显著。每组各亚型的5年生存率分别为94%、82%和91%(P = 0.002);93.5%、81%和89%(P < 0.001);84%、77%和83%(P = 0.035)。Cox回归多因素分析显示,与二甲双胍组相比,非二甲双胍组的所有三种亚型预后均较差(风险比[HR],3.579;95%置信区间[CI],1.506 - 8.506[P = 0.004];HR,3.232;95% CI,1.839 - 5.678[P < 0.001];HR,2.034;95% CI,1.019 - 4.059[P = 0.044],分别对应腔面A型、腔面B型(高ki67)和腔面B型(her-2/neu+))。与二甲双胍组相比,糖尿病组仅腔面B型(高ki67)亚型预后较差(HR,1.762;95% CI,1.033 - 3.005[P = 0.038])。此外,对于腔面A型、腔面B型(高ki67)和腔面B型(her-2/neu+)亚组,二甲双胍组和非二甲双胍组中老年患者(P < 0.001)和绝经后患者(P < 0.001)的比例高于非糖尿病组。而且,二甲双胍组和非二甲双胍组患心血管和脑血管疾病的概率也更高(P < 0.001)。对于腔面B型(高ki67)和腔面B型(her-2/neu +)亚组,二甲双胍组和非二甲双胍组肥胖患者的比例更高(P < 0.001)。在临床特征方面,对于腔面B型(高ki67)亚型,非二甲双胍组浸润性导管癌患者的比例低于其他两组(P = 0.001)。与非糖尿病组相比,二甲双胍组和非二甲双胍组中T3/4期患者的比例更高(P < 0.001),淋巴结转移患者的比例更高(P = 0.001),血管癌栓患者的比例更高(P = 0.001)。总之,与二甲双胍组相比,非二甲双胍组的所有腔面型乳腺癌亚型预后均较差。在糖尿病组中,仅腔面B型(高ki67)亚型患者预后较差。因此,不同的糖尿病用药可能对不同亚型的腔面型乳腺癌预后产生不同影响。

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