【作者】 刘鹏；

【导师】 刘剑仑；

【作者基本信息】 广西医科大学 ， 肿瘤学乳腺外科（专业学位）， 2013， 硕士

【摘要】 背景：乳腺癌是目前世界范围内最高发的恶性肿瘤之一,在我国,乳腺癌在城市女性恶性肿瘤中发病率最高,且呈逐年上升趋势[1],基于乳腺癌是一种全身性疾病的共识,化疗在乳腺癌的综合治疗中占据着极其重要的位置。60年代随着CMF方案的出现,乳腺癌的5年无病生存率(DFS)提高到53%,总生存率(OS)提高到70%。而70年代出现的蒽环类药物则进一步把乳腺癌的5年无病生存率提高到63%,总生存率提高到77%[1]。并由此奠定了蒽环类药物在乳腺癌化疗中的地位。但是因为蒽环类药物具有比较强的心脏毒性及有一个终身耐受剂量,使肿瘤专科医生倍受困扰,因此,区分是否能从蒽环类药物中获益的亚组人群变得十分重要。已经有药物基因组学研究结果表明：乳腺癌TOP2A基因的扩增极有可能是蒽环类药物疗效可靠的预测指标。TOP2A基因扩增的患者大多存在于HER-2基因扩增的患者中,对乳腺癌患者进行TOP2A基因扩增检测有可能区分出对蒽环类药物更加敏感的亚组人群[1-3]。目的：探讨乳腺癌TOP2A基因的表达及其与基于蒽环类药物新辅助化疗疗效之间的关系。资料和方法：收集了广西壮族自治区肿瘤医院乳腺外科2010年2月至2012年1月收治的新辅助化疗患者50例标本,采用免疫组化方法检测所有患者新辅助化疗前后的癌组织TOP2A表达情况,全组患者均采用含蒽环类方案行新辅助化疗,化疗四周期后采用RECIST标准及病理缓解情况来评估化疗效果。根据临床及病理缓解情况,利用SPSS13.0统计软件,分析TOP2A表达与临床及病理有效率之间的关系,从而得出TOP2A蛋白表达情况与含蒽环类方案新辅助化疗疗效之间的关系。结果：本研究纳入的50例乳腺癌患者组织标本中,在基于蒽环类药物的新辅助化疗中,全组临床客观有效率(ORR)为84%(42/50),病理缓解有效率为94%(47/50)。同时我们采用的临床级病理评价标准具有一致性,可共同作为评价新辅助化疗疗效的指标。全组50例患者中,TOP2A基因表达17例(17/50,34%),TOP2A基因未表达33例(33/50,66%)。其中TOP2A表达的17例患者中17例均为临床有效(有效率100%)；TOP2A未表达的33例患者中25例有效(有效率75.8%), TOP2A表达组的17例患者中病理评估为4-5级的占到64.7%(11/17),明显优于TOP2A未表达组的9.0%(3/33),TOP2A表达时化疗有效率更高。全组50例患者中,HER-2基因表达25例(25/50,50%),未表达25例(25/50,50%)。在HER-2基因表达的25例患者中24例为临床有效(有效率96%)；HER-2基因未表达的25例患者中18例为临床有效(有效率72%),HER-2基因表达组的25例患者中病理评估为4-5级的占44%(11/25),HER-2基因未表达组的25例患者中病理评估为4-5级的占12%(3/25)。HER-2表达时蒽环类药物新辅助化疗化疗临床有效率更高。本研究还发现,TOP2A与HER-2的表达具有正相关性,且HER-2及TOP2A共同表达的病例为12例,与化疗效果经相关性分析后发现HER-2及TOP2A共同表达,能从蒽环类药物新辅助化疗中获益(rs=0.642,P＜0.05)。结论：乳腺癌组织中TOP2A蛋白的表达对基于蒽环类药物的新辅助化疗的疗效有正相关预测作用。更多还原

【Abstract】 Background:Breast cancer is one of the most common malignant tumor in the world. In our country, breast cancer accounts for first female malignancy incidence in major cities, and the incidence rate has continued to rise.Based on the breast cancer is a systemic disease by the globalization consensus, chemotherapy in the treatment of breast cancer occupies an extremely important position. From1960s, the CMF improved the5-year disease-free survival(DFS) of breast cancer to53%, the overall survival(OS) rate increased to70%. The anthracycline further5-year disease-free survival (DFS) of breast cancer increased to63%from the1970s, the overall survival(OS) rate increased to77%. And thus laid the backbone of the position of the anthracycline in breast cancer chemotherapy. But its cardiotoxicity has been plagued by cancer specialists for a long time. The problem urgently needed to resolved is distinguish the subgroup who can get benfit. The Pharmacogenomics research indicate that in breast cancer, the amplification of the TOP2A may be a reliable predictor factor of the efficacy of the anthracyclines. Most patients with TOP2A gene amplification also with HER-2gene amplification in breast cancer.Patients with HER-2gene amplification, to detect the TOP2A gene amplification may possible to distinguish the anthracycline sensitivity sub-group. Objective:Investigate the expression of TOP2A gene and its relationship with the neo-adjuvant chemotherapy based on anthracycline in breast cancer.Methods:To collected50specimens of Guangxi Tumor Hospital, Breast Surgery department from February2010to June2012, all patients with neo-adjuvant chemotherapy.TO detect HER-2and TOP2A expression by immunohistochemistry from cancer tissue befor chemotherapy. The whole group of patients were treated with neo-adjuvant chemotherapy based on anthracycline According to the clinical and pathological response, analysis the relationship of HER-2or TOP2A amplification and the efficacy of neoadjuvant chemotherapy basde on anthracyclines.Result:This study included50patients with breast cancer tissue samples, the neoadjuvant chemotherapy based on anthracycline.The clinical objective response rate (ORR) was84%(42/50), pathological response rate was94%(47/50). The clinical and pathological evaluation criteria was consistent.TOP2A gene expression in17cases (17/50,34%), and is not expressed in33cases (33/50,66%). The17patients of TOP2A expression all get clinically effective(100%) and the33patients without TOP2A expression was only25cases (75.8%). The pathological assessment of grade4-5in TOP2A expression group of17patients accounted for64.7%(11/17), significantly better than9.0%(3/33) of Control group.HER-2gene expression in25cases (25/50,50%), and is not expressed in25cases (25/50,50%). In the25patients of HER-2expression,24get clinically effective(96%) and the25patients without HER-2expression was only18cases (72%). The pathological assessment of grade4-5in HER-2expression group of25patients accounted for44.0%(11/25), significantly better than12.0%(3/25) of Control group. This study also found a positive correlation between TOP2A and HER-2expression. The cases of HER-2and TOP2A co-expression was12. Use the spearman rank correlation analysis we found that the co-expression of HER-2and TOP2A could get benefit from anthracyclines.(rs=0.642, P<0.05),Conclusions:The expression of TOP2A gene in breast cancer get positive correlation prediction from neo-adjuvant chemotherapy based on anthracycline.更多还原