P53蛋白过表达可预测雌激素受体阳性，早期绝经后乳腺癌对芳香化酶抑制剂治疗的敏感性

Overexpression of P53 is prognostic for aromatase inhibitor resistance in early stage postmenopausal patients with ER-positive breast cancer

背景与目的：抑癌基因P53在肿瘤中的研究一直是热点，包括乳腺癌。对于P53基因和乳腺癌预后的研究很多，多数研究表明P53蛋白表达是乳腺癌的不良预后因素之一。而目前对于P53蛋白表达在雌激素受体（estrogen receptor，ER）阳性，早期绝经后乳腺癌对芳香化酶抑制剂（aromotase inhibitors，AI）的敏感性的作用尚无明确结论。本研究旨在探讨P53蛋白表达在ER阳性，早期绝经后乳腺癌对AI治疗敏感性的预测作用。方法：收集2000年1月—2006年12月间复旦大学附属肿瘤医院乳腺外科住院的患者资料共293例。所有患者均接受AI治疗。中位随访时间为72个月（6-140个月）。分析不同P53表达状态对无病生存率（disease free survival，DFS）的影响。应用统计学方法进行生存分析及Cox回归模型进行单因素和多因素分析。结果：P53阳性和P53阴性患者的5年生存率分别为78%和89%。多因素回归分析显示P53表达状态（HR=1.729，95%CI：1.038-2.880，P=0.035）、病理分期（HR=2.270，95%CI：1.399-3.681，P=0.001）、组织学分级（HR=2.328，95%CI：1.312-4.133，P=0.004）及年龄（HR=1.988，95%CI：1.511-2.617，P＆lt;0.005）是接受AI治疗的早期乳腺癌复发转移的独立危险因素。结论：P53蛋白表达可预测ER阳性，早期绝经后乳腺癌对AI治疗的敏感性；其可能成为决定绝经后激素受体阳性乳腺癌患者治疗策略的关键因素。

Background and purpose：Tumor suppressor gene P53 has long been studied in tumors, including breast cancer. More studies focused on the relationship between P53 and prognosis of breast cancer and found that P53 overexpression suggested a bad prognosis. However, the effect of P53 on early stage postmenopausal patients with ER-positive breast cancer has not been clariifed yet. This study was to investigate the role of P53 plays in aromatase inhibitor （AI） resistance among early stage postmenopausal patients with ER-positive breast cancer patients. Methods：A total number of 293 operable breast cancer patients who received surgical treatment during Jul. 2000 to Jul. 2006 in Fudan University Shanghai Cancer Center were enrolled into this study. All patients received AI treatment. The SPSS 12.0 software was used to estimate the survival rate. Univariate and multivariate analysis were also performed via above software. Results：The median follow-up time is 72 months （6-140 months）. The 5 year disease free survival （DFS） of P53 positive and negative were 78%and 89%. The results showed that P53 overexpression （HR=1.729, 95%CI：1.038-2.880, P=0.035）, pathological stage （HR=2.270, 95%CI：1.399-3.681, P=0.001）;histological grade （HR=2.328, 95%CI：1.312-4.133, P=0.004）; age （HR=1.988, 95%CI：1.511-2.617, P〈0.005） were still the independent risk factors of recurrence and metastasis in breast cancer patients treated with AI. Conclusion：P53 overexpression correlated strongly with AI resistance in early stage postmenopausal patients with ER-positive breast cancer patients who were treated with AI and conifrmed the relevance of previously described prognostic factors. It is reasonable to take P53 expression into account when we evaluate the risk of breast cancer patients and decide the anti-cancer treatment strategy.