人表皮生长因子受体2（HER2）与拓扑异构酶IIα：乳腺癌患者新辅助化疗反应的可能预测指标

HER2 and topoisomerase IIalpha: possible predictors of response to neoadjuvant chemotherapy for breast cancer patients.

作者信息

Zhu Li, Li Ya-fen, Chen Wei-guo, He Jian-rong, Peng Chen-hong, Zhu Zheng-gang, Li Hong-wei

机构信息

Department of Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.

出版信息

Chin Med J (Engl). 2008 Oct 20;121(20):1965-8.

PMID:19080257

Abstract

BACKGROUND

Surrogate markers may be used to assess the response to neoadjuvant treatment. The association between HER2 overexpression and favorable response to specific therapy in breast cancer is controversial, and the mechanism unclear. The purpose of the study was to evaluate HER2 and topoisomerase IIalpha (Topo IIalpha) as candidates for predicting the response to neoadjuvant chemotherapy in breast cancer patients.

METHODS

Between 1999 and 2006, seventy-six breast cancer patients who had received neoadjuvant chemotherapy were studied. Regimens including either CEF (cyclophosphamide, epirubicin, 5-fluorouracil) or CMF (cyclophosphamide, methotrexate, 5-fluorouracil) were given in more than three cycles to this group of patients. Protein expression of HER2 and Topo IIalpha were determined by immunohistochemistry. The primary endpoint was pathological and clinical response.

RESULTS

Of 76 primary breast cancer samples, 27 (35.5%) showed overexpression of either HER2 (25%) or Topo IIalpha protein (10.5%), whereas in 7 tumors (9.2%) both proteins were found to be overexpressed. Ten patients (13.2%) had a clinical complete response and 21 (27.6%) had a clinical partial response. Five women (6.6%) had a pathological complete response, 5 (6.6%) had microscopic residual disease, and 46 (60.5%) had macroscopic residual disease. HER2 and Topo IIalpha overexpression was significantly associated with a favorable response (P < 0.001 and P = 0.005 respectively).

CONCLUSION

Our study suggests that HER2 and Topo IIalpha overexpression could be predictors of the response to neoadjuvant chemotherapy in both the CEF and CMF arms.

摘要

背景

替代标志物可用于评估新辅助治疗的反应。HER2过表达与乳腺癌对特定治疗的良好反应之间的关联存在争议，其机制尚不清楚。本研究的目的是评估HER2和拓扑异构酶IIα（Topo IIα）作为预测乳腺癌患者新辅助化疗反应的候选标志物。

方法

1999年至2006年期间，对76例接受新辅助化疗的乳腺癌患者进行了研究。该组患者接受了超过三个周期的包括CEF（环磷酰胺、表柔比星、5-氟尿嘧啶）或CMF（环磷酰胺、甲氨蝶呤、5-氟尿嘧啶）的化疗方案。通过免疫组织化学测定HER2和Topo IIα的蛋白表达。主要终点是病理和临床反应。

结果

在76例原发性乳腺癌样本中，27例（35.5%）显示HER2（25%）或Topo IIα蛋白（10.5%）过表达，而在7例肿瘤（9.2%）中发现两种蛋白均过表达。10例患者（13.2%）有临床完全缓解，21例（27.6%）有临床部分缓解。5名女性（6.6%）有病理完全缓解，5名（6.6%）有微小残留病灶，46名（60.5%）有肉眼可见残留病灶。HER2和Topo IIα过表达与良好反应显著相关（分别为P < 0.001和P = 0.005）。