Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients
Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients
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DOI：
10.1007/s00280-011-1777-7
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发表时间：
2012-04-01
影响因子：
3
通讯作者：
Kasumi, Fujio
中科院分区：
文献类型：
--
作者：
Nakai, Katsuya;Mitomi, Hiroyuki;Kasumi, Fujio
目的评价生物标志物在预测局部晚期基底样乳腺癌（blbc）患者新辅助化疗（NACT）病理完全缓解（pCR）中的重要性。患者和方法本研究纳入32例接受NACT治疗的BLBC患者，该患者采用蒽环类药物加紫杉烷方案。观察NACT前后MGMT、MLH1、MSH2、BRCA1的免疫反应性。结果32例中有10例（31%）获得pCR。pCR组的肿瘤相关生存率（P = 0.013）和无病生存率（P = 0.023）显著高于非pCR组。在NACT前的活检样本中，MGMT、MLH1、MSH2和BRCA1的表达分别在12/32（38%）、0/32（0%）、5/32（16%）和28/32（88%）中减弱。在评估pCR、患者的特征（患者的年龄、绝经状态或临床和病理分期）和免疫组织化学模式时，MGMT的减弱表达仅被发现能显著预测pCR （P = 0.018）。19例非pcr患者可获得NACT前的成对活检样本和NACT后的手术肿瘤材料。在这些病例中，与MLH1、MSH2或BRCA1相比，在NACT期间MGMT表达下降的频率更高（P = 0.021）。结论MGMT状态是新辅助蒽环类药物+紫杉烷联合化疗pCR的预测因素，可能有助于日本BLBC患者选择合适的NACT。
Purpose To evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in patients with locally advanced basal-like breast cancers (BLBCs).Patients and methods Thirty-two BLBC patients receiving NACT with an anthracycline-based regimen plus taxane were included in this study. The immunoreactivities of MGMT, MLH1, MSH2 and BRCA1 before and after NACT were evaluated.Results A pCR was obtained in 10 of 32 cases (31%). Cancer-related (P = 0.013) and disease-free (P = 0.023) survival rates were significantly higher in the pCR group than in the non-pCR group. In biopsy samples before NACT, attenuated expression of MGMT, MLH1, MSH2 and BRCA1 was observed in 12/32 (38%), 0/32 (0%), 5/32 (16%) and 28/32 (88%) cases, respectively. On evaluation of pCR, patients' characteristics (patients' age, menopausal status, or clinical and pathological stages) and immunohistochemical patterns, attenuated expression of MGMT was only found to be significantly predictive of a pCR (P = 0.018). Paired biopsy sample before NACT and a surgical tumor material after NACT were available for 19 cases of non-pCR. In these cases, decrease in expression during NACT were more frequently observed for MGMT as compared to MLH1, MSH2 or BRCA1 (P = 0.021).Conclusions MGMT status is a predictive factor for pCR with neoadjuvant anthracycline-based plus taxane combination chemotherapy, which may be helpful in the selection of appropriate NACT for Japanese patients with BLBC.