目的 观察PI3 K/mTOR通路状态与乳腺癌新辅助化疗疗效之间的关系.方法 对2009年1月至2010年11月在北京大学第一医院乳腺疾病中心接受4～6个周期包含紫杉方案新辅助化疗的105例乳腺癌患者资料进行回顾性分析.用免疫组织化学方法检测新辅助化疗前肿瘤病灶PTEN、p-AKT( Ser473)和p-mTOR( Ser2448)的表达情况,用术后病理评价新辅助化疗疗效,病理学反应级别为G4、病理完全缓解(PCR)则认为化疗有效.通过x2检验、Fisher精确概率法和双边Logistic 回归探讨上述指标与新辅助化疗疗效之间的相关性.结果 105例患者中新辅助化疗有效率为58.1％ (61/105),其中PCR占27.6％ (29/105).PTEN、p-AKT和p-mTOR的阳性表达率分别为52.4％ (55/105)、68.6％ (72/105)、43.8％ (46/105).x2检验、Fisher精确概率法分析表明p-mTOR 与新辅助化疗疗效相关(P =0.003),与获得PCR相关(P=0.001)；双边Logistic回归表明p-mTOR是新辅助化疗疗效和获得PCR(均P＜0.01)的独立预测指标.p-AKT与p-mTOR表达水平差异有统计学意义(P=0.000).p-AKT与PR表达差异同样有统计学意义(P =0.035).结论 p-mTOR状态对于包含紫杉方案的新辅助化疗有预测意义,高表达患者疗效差,低表达患者更多地从化疗中获益.
Objective To explore the relationship between the status of PI3K/mTOR pathway and the therapeutic efficacies of neoadjuvant chemotherapy for breast cancer.Methods A total of 105 patients receiving 4 -6 cycles of taxane-based neoadjuvant chemotherapy at our centre between January 2009 and November 2010 were recruited into this retrospective study.The expressions of PTEN,p-AKT (Ser473) and p-mTOR (Ser2448) were detected by immunohistochemistry before neoadjuvant chemotherapy. We employed pathology to evaluate the therapeutic efficacies and considered complete response (G4) & pathologic complete response (PCR) as efficacious.Fourfold table Chi-square test and binary Logistic regression were used to analyze the relationship between the above features and therapeutic efficacies.Results The overall efficacy rate of neoadjuvant chemotherapy was 58.1％ (61/105) and the PCR rate 27.6％ (29/105).The positive expression rates of PTEN,p-AKT and p-mTOR were 52.4％ (57/105),68.6％ (72/105) and 43.8％ (46/105) respectively.Fourfold table Chi-square test showed the difference between p-mTOR and therapeutic efficacy was significant statistically ( P =0.003 ) and also the difference between pmTOR and PCR ( P =0.001 ). Binary Logistic regression showed the difference between p-mTOR and therapeutic efficiency was significant statistically,and also the difference between p-mTOR and PCR (both P ＜ 0.01 ).The differential expressions of p-mTOR and p-AKT were statistically significant (P =0.000) and so were those of p-AKT and PR (P =0.035).Conclusions The status of p-mTOR has predictive values for taxane-based neoadjuvant chemotherapy. The patients with a low level of p-mTOR are more responsive to thermotherapy while those with a high level of p-mTOR have a worse efficacy.