乳腺癌分子分型与多西他赛密集新辅助化疗疗效及预后的关系研究

摘要

Objective To investigate the relationship between different molecular subtypes and the therapeutic effect and prognosis of dose dense docetaxel neoadjuvant chemotherapy in breast cancer. Methods 82 breast cancer patients admitted to our hospital from March 2007 to March 2010 were given four cycles of docetaxel chemotherapy ( 75 mg/m , with two weeks as a cycle ), followed by surgical operation. After operation, the patients were given four cycles of EC chemotherapy ( with EPI 75 mg/m , CTX 600 mg/m and two weeks as a cycle ) . Immunohistochemical studies and fluorescence in -situ hybridization were performed to detect the expression of estrogen receptor ( ER ), progesterone receptor ( PR ), Her - 2 and Ki67 of breast cancer before treatment. The patients were classified into 4 subtypes: luminal A, luminal B, Her -2 + and triple negative. The therapeutic effect and prognosis of the four subtypes after dose dense docetaxel neoadjuvant chemotherapy were analyzed. Results Of the total 82 patients, the overall response rate ( RR ) was 89. 0% ( 73/82 ), including 17 cases of complete response ( CR ), 56 cases of partial response ( PR ), 9 cases of stable disease ( SD ) and no progression of disease ( PD ) . FISH were performed to detect 11 cases of IHC scores of 2 + . There were 5 cases for the overexpression of Her -2. According to the results of immunohis- tochemical studies and FISH method on the expression of ER, PR, Her -2 and Ki67, there were 39 cases ( 47. 6% ) of Luminal A, 19 cases ( 23. 2% ) of Luminal B, 11 cases ( 13. 4% ) of Her - 2 + and 13 cases ( 15. 9% ) of triple negative. The age, tumor size, lymph node metastasis, histological type and surgical style among breast cancer patients with different molecular subtypes showed no statistically significant differences ( P > 0. 05 ) . The RR of luminal A, luminal B, Her - 2 + and triple negative were 84. 6% ( 33/39 ), 84. 2% ( 16/19 ), 100. 0% ( 11/11 ) and 100. 0% ( 13/13 ) respectively, and the difference was not statistically significant ( χ2 =4. 185 , P =0. 242 ) . Until June 2012, the three - year disease - free survival ( DFS ) and overall survival ( OS ) of the 82 patients were 85% and 88% respectively, and the differences between the four subtypes were statistically significant ( χ2 =9. 584 and 9. 414, P <0. 05 ) . The three -year DFS and OS of Luminal A subtype showed statistically significant differences compared with Her -2 + and triple negative ( P < 0. 05 ) . Conclusion The therapeutic effect of 75 mg/m one - drug dose dense docetaxe neoadjuvant chemotherapy on luminal A, luminal B, Her - 2 + and triple negative are similar. However, the prognosis of luminal A was better than those of the Her -2 + and triple negative.%目的 探讨乳腺癌不同分子亚型与多西他赛密集新辅助化疗疗效及预后的关系.方法 选取2007年3月-2010年3月我院收治的手术治疗的乳腺癌患者82例为研究对象,行4周期多西他赛(75 mg/m2,每2周为1周期)方案化疗,随后行外科手术治疗,术后再行4周期EC[表阿霉素(EPI)75 mg/m2,环磷酰胺(CTX)600 mg/m2,每2周为1周期]方案化疗;依据免疫组化方法及荧光原位杂交(FISH)法检测新辅助化疗前肿瘤病灶雌激素受体(ER)、孕激素受体(PR)、Her-2及Ki67的表达水平,将乳腺癌分为Luminal A亚型、Luminal B亚型、Her-2+亚型及三阴性亚型4型,分析4型乳腺癌在多西他赛密集新辅助化疗后的疗效及预后的差别.结果 82例患者均可评价疗效,完全缓解(CR)17例,部分缓解(PR)56例,稳定(SD)9例,无进展(PD)患者,有效率(RR)为89.0%(73/82).11例免疫组化示Her-2染色(++)的患者行FISH测定,5例Her-2为过表达,根据免疫组化法及FISH法检测ER、PR、Her-2和 Ki67的表达进行乳腺癌分子分型,Luminal A亚型39例(47.6%),Luminal B亚型19例(23.2%),Her-2+亚型11例(13.4%)及三阴性亚型13例(15.9%);不同乳腺癌分子分型患者的年龄、肿瘤大小、淋巴结转移、组织学类型及外科手术类型比较,差异均无统计学意义(P>0.05).Luminal A亚型、Luminal B亚型、Her-2+亚型及三阴性亚型的RR分别为84.6%(33/39)、84.2%(16/19)、100.0%(11/11)、100.0%(13/13),不同乳腺癌分子分型患者RR比较,差异无统计学意义(χ2=4.185,P=0.242).截至2012年6月82例乳腺癌患者3年无病生存率(DFS)、总生存率(OS)分别为85%、88%.Luminal A亚型、Luminal B亚型、Her-2+亚型、三阴性亚型的3年DFS及OS比较,差异有统计学意义(χ2值分别为9.584和9.414,P<0.05);其中Luminal A亚型与Her-2+亚型、Luminal A亚型与三阴性亚型的3年DFS及OS比较,差异均有统计学意义(P<0.05).结论 单药75 mg/m2多西他赛密集新辅助化疗对Luminal A亚型、Luminal B亚型、Her-2+亚型及三阴性亚型疗效相似,但Luminal A亚型比Her-2 +亚型、三阴性亚型预后更好.