论文摘要
[背景]新辅助化疗已成为局部晚期乳腺癌的标准初始治疗方案，新辅助化疗的疗效是病人长期生存率的重要预后标志，以往的研究提示拓扑异构酶Ⅱα基因（TOPO Ⅱα）可能与蒽环类为主的新辅助化疗疗效相关，可用作预测化疗敏感性的标志。近期研究显示c-myc基因扩增可能与乳腺癌的化疗耐药性相关。本研究的目的是通过前瞻性研究检验TOPO Ⅱα、c-myc基因以及临床、病理指标与乳腺癌新辅助化疗疗效的相关性，以寻找可用于预测乳腺癌新辅助化疗疗效的生物学标志。 [病人与方法]本研究分两部分，第一部分，应用荧光原位杂交技术（FISH）对82例术前未经治疗的乳腺癌进行TOPO Ⅱα与c-myc基因检测，并检验TOPO Ⅱα、c-myc基因扩增与乳腺癌临床病理指标的相关性。第二部分，41例原发肿瘤≥3cm的乳腺癌病人，手术前接受4周期EC方案（表阿霉素80 mg／m2，环磷酰胺600mg／m2）新辅助化疗，化疗后分别进行临床疗效评价（RECIST标准）与病理学疗效评价（Miller／Payne分级）。在新辅助化疗前获得肿瘤细胞印片标本，应用FISH与免疫细胞化学技术分别检测TOPO Ⅱα与c-myc的基因扩增与蛋白表达，然后检验TOPO Ⅱα及c-myc基因与新辅助化疗疗效的相关性，同时检验各临床、病理指标（包括病人年龄、月经状态、肿瘤大小、淋巴结转移、分期、激素受体、c-erbB2）与新辅助化疗疗效的相关性。统计学分析应用SPSS 11.5软件包。 [结果]术前未经治疗的82例乳腺癌中TOPO Ⅱα与c-myc基因的扩增率分别为21.9％与47.6％，基因扩增与乳腺癌各临床、病理指标均无相关性（P＞0.05）。新辅助化疗的41例乳腺癌中，肿瘤c-myc基因扩增、病人年龄、月经状态均与乳腺癌新辅助化疗病理学疗效相关，c-myc基因扩增的乳腺癌新辅助化疗后病理学疗效较无扩增的肿瘤差（P=0.04），年龄≥50岁或绝经后病人新辅助化疗病理学疗效较50岁以下与绝经前病人差（P=0.014与0.036）；雌激素受体强阳性表达的乳腺癌新辅助化疗后临床有效率低于阴性与弱阳性表达的病人（P=0.018）；TOPO Ⅱα基因扩增、
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