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MGMT、hMLH1、hMSH2 和 BRCA1 蛋白表达对基底样乳腺癌患者新辅助化疗病理完全缓解的预测价值。

Predictive value of MGMT, hMLH1, hMSH2 and BRCA1 protein expression for pathological complete response to neoadjuvant chemotherapy in basal-like breast cancer patients.

机构信息

Department of Breast Oncology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.

出版信息

Cancer Chemother Pharmacol. 2012 Apr;69(4):923-30. doi: 10.1007/s00280-011-1777-7. Epub 2011 Nov 15.

Abstract

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.

摘要

目的

评估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。

方法

本研究纳入 32 例接受蒽环类联合紫杉类方案 NACT 的 BLBC 患者。评估 NACT 前后 MGMT、MLH1、MSH2 和 BRCA1 的免疫反应性。

结果

32 例中有 10 例(31%)获得 pCR。pCR 组的癌症相关(P = 0.013)和无病生存(P = 0.023)率明显高于非 pCR 组。在 NACT 前的活检样本中,分别有 12/32(38%)、0/32(0%)、5/32(16%)和 28/32(88%)例患者的 MGMT、MLH1、MSH2 和 BRCA1 表达减弱。在评估 pCR 时,患者特征(患者年龄、绝经状态或临床和病理分期)和免疫组化模式,仅发现 MGMT 表达减弱与 pCR 显著相关(P = 0.018)。19 例非 pCR 患者的 NACT 前活检样本和 NACT 后手术肿瘤标本均可获得。在这些病例中,与 MLH1、MSH2 或 BRCA1 相比,MGMT 在 NACT 期间的表达下降更为常见(P = 0.021)。

结论

MGMT 状态是预测蒽环类联合紫杉类方案新辅助化疗 pCR 的预测因子,这可能有助于选择合适的 NACT 治疗日本 BLBC 患者。

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