晚期乳腺癌患者病灶之间ER、PR及HER-2表达异质性的研究

发布时间：2018-06-20 03:10

  本文选题：原发性乳腺癌 + 转移性乳腺癌　； 参考：《浙江大学》2017年硕士论文

【摘要】：背景:乳腺癌是女性最常见的恶性肿瘤之一,流行病学数据表明其发病率逐年上升。晚期转移性乳腺癌(metastatic breast cancer,MBC)的治疗仍远未达到理想水平,应用目前常规治疗手段如化疗、放疗、内分泌治疗及靶向治疗仍难以治愈,治疗后平均中位存活时间为2-3年,仅少数患者可长期生存。Ⅳ期乳腺癌患者治疗原则是以内科药物治疗为主的综合治疗。目前,转移性乳腺癌的治疗主要是根据肿瘤细胞表面ER、PR和HER-2三种受体的不同表达情况,从而进一步选择相应的内分泌、化疗、靶向及相互联合治疗等不同的治疗策略。已有多个回顾性研究报导了与乳腺癌原发灶相比,乳腺癌复发/转移灶中存在3种受体表达不一致的现象;甚至同一乳腺癌患者不同复发/转移部位之间、双侧乳腺癌病灶之间存在ER、PR和HER-2三种受体的异质性表达。上述现象进一步影响了患者的预后及治疗方案的选择。目的:探讨本中心乳腺癌复发/转移病灶与原发病灶之间3种受体表达不一致的情况。进一步探讨患者年龄、出现病灶复发/转移的间隔时间、先前治疗如内分泌、化疗及靶向治疗等因素与3种受体表达不一致是否相关。方法:回顾性分析2013.9至2016.12月在浙江大学附属邵逸夫医院就诊的晚期乳腺癌患者,分析其原发灶手术标本与复发及远处转移标本中肿瘤细胞表面ER、PR和HER-2的表达情况,回顾性分析其与患者年龄、出现病灶复发/转移的间隔时间、先前治疗如内分泌、化疗及靶向治疗等因素的相关性。结果:本研究共分析了 96例接受再次及多次活检的晚期乳腺癌患者病灶肿瘤细胞表面3种受体表达的情况。96例晚期乳腺癌患者就诊时的平均年龄为49岁(33岁～76岁)。所有患者原发乳腺癌均进行了乳腺癌根治或改良根治术,96例患者术后进行了相应的辅助治疗如放疗、内分泌治疗和化疗治疗,6例患者术后曾行赫赛汀靶向治疗。ER、PR和HER2在原发乳腺肿瘤病灶与复发转移灶中存在表达不一致性的现象,不一致率分别为20%、34%、13%。患者的年龄、出现复发/转移间隔时间、先前治疗如内分泌治疗、化疗及靶向治疗等因素与3种受体表达不一致无明显相关。因发现乳腺原发肿瘤与转移灶中相关受体表达不一致情况后,导致的潜在治疗方案调整率约为23%。结论:研究发现同一乳腺癌患者中乳腺原发灶与复发/转移灶之间存在ER、PR和HER2三种受体表达不一致性的现象,可能会进一步影响患者的后续治疗方案。因此,研究结论认为在临床可能的情况下,应对晚期乳腺癌患者复发或转移病灶进行再次活检以明确受体表达情况。
[Abstract]:Background: breast cancer is one of the most common malignant tumors in women. Epidemiological data show that the incidence of breast cancer is increasing year by year. The treatment of advanced metastatic breast cancer is still far from the ideal level, and the median survival time is 2-3 years after treatment with conventional treatment methods such as chemotherapy, radiotherapy, endocrine therapy and targeted therapy. Only a few patients can survive for a long time. At present, the treatment of metastatic breast cancer is mainly based on the different expression of ERP PR and HER-2 receptors on the surface of tumor cells, so as to further select different treatment strategies such as endocrine, chemotherapy, targeting and combined therapy. A number of retrospective studies have reported that there are three different expressions of receptors in the recurrence / metastasis of breast cancer compared with the primary breast cancer, even among different recurrence / metastasis sites in the same breast cancer patients. There is heterogeneity expression of ERP PR and HER-2 receptors between bilateral breast cancer lesions. These phenomena further affect the prognosis and treatment options. Objective: to investigate the different expression of three receptors between recurrent / metastatic lesions and primary lesions of breast cancer in our center. To further investigate the age of the patients, the interval between recurrence and metastasis, and whether the factors such as endocrine, chemotherapy and targeted therapy were not related to the expression of the three receptors. Methods: the expression of ERP PR and HER-2 on tumor cells were analyzed retrospectively in patients with advanced breast cancer from 2013.9 to December 2016 in the hospital affiliated to run Shaw University of Zhejiang University, and the expression of ERPR and HER-2 on the tumor cell surface in the primary tumor, recurrence and distant metastasis specimens were analyzed. The correlation between the age of patients, the interval between recurrence and metastasis, and the factors such as endocrine, chemotherapy and targeted therapy were analyzed retrospectively. Results: the expression of 3 receptors on tumor cells in 96 patients with advanced breast cancer were analyzed. The mean age of 96 patients with advanced breast cancer was 49 years old, 33 years old and 76 years old. All patients with primary breast cancer underwent radical mastectomy or modified radical mastectomy. 96 patients underwent postoperative adjuvant therapy such as radiotherapy. Six patients with endocrine therapy and chemotherapy had been treated with Herceptin targeted therapy. ERP and HER2 were not consistent in primary breast tumor focus and recurrence and metastasis. The inconsistent rates were 200.3434 and 1313 respectively. Age, recurrence / metastasis interval, previous treatment such as endocrine therapy, chemotherapy and targeted therapy were not significantly correlated with the expression of the three receptors. The potential therapeutic regimen adjustment rate due to the inconsistent expression of related receptors in primary breast tumors and metastases is about 23.3%. Conclusion: it is found that the expression of ERPR and HER2 receptors is inconsistent between the primary breast cancer and the recurrence / metastasis in the same breast cancer patients, which may further affect the subsequent treatment of the patients. Therefore, the study concluded that if it is clinically possible, patients with advanced breast cancer should be re-biopsied to determine the expression of receptors.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9
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本文编号：2042667