Influence of Neoadjuvant Chemotherapy on HER2/neu Status in Invasive Breast Cancer
Influence of Neoadjuvant Chemotherapy on HER2/neu Status in Invasive Breast Cancer
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DOI：
10.1016/j.clbc.2012.09.011
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发表时间：
2013-02-01
影响因子：
3.1
通讯作者：
Wang, Zhe
中科院分区：
文献类型：
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作者：
Li, Peifeng;Liu, Tantan;Wang, Zhe
乳腺癌新辅助化疗可能导致HER2/neu蛋白表达降低，这可能反映了乳腺癌对化疗的敏感性，并可能成为预测病理完全缓解的指标。然而，它们具有稳定的HER2/neu基因扩增状态。因此，应考虑重新检测新辅助化疗(NAC)后残留肿瘤中HER2/neu的免疫组织化学(IHC)状态，以优化术后辅助治疗。在这项回顾性队列研究中，评估了NAC对浸润性乳腺癌HER2/neu状态的影响，并对相关因素进行了分析。患者和方法：131例原发性乳腺癌患者接受了以蒽环类药物和/或紫杉烷为基础的NAC治疗。用免疫组织化学方法检测NAC前的原发肿瘤组织、NAC术后残留乳腺癌或肿瘤阳性腋窝淋巴结标本的HER2/neu状态。对32对HER2/neu IHC评分不一致的标本进行荧光原位杂交(FISH)分析。结果：在接受NAC的患者中，核心针活检和手术切除标本的IHC检测HER2/neu状态有显著差异。NAC治疗后，23.4%(29/124)的肿瘤HER2/neu表达被IHC下调。HER2/neu IHC评分的改变与肿瘤亚型、对NAC的病理反应、辅助方案或从最后一次化疗到手术的时间间隔没有显著相关性。HER2/neu蛋白过表达水平与对以蒽环类药物和紫杉烷为基础的化疗的良好病理反应有关。然而，NAG后HER2/neu IHC评分改变的肿瘤，FISH分析显示HER2/neu基因扩增/不扩增稳定。结论：免疫组化检测乳腺癌新辅助化疗后HER2/neu基因状态发生改变，FISH检测HER2/neu基因扩增状态稳定。HER2/neu蛋白的过度表达表明对新辅助的基于蒽环类和紫杉烷的化疗更敏感。因此，应考虑重新检测NAG后残留肿瘤中的HER2/neu IHC状态，以优化辅助系统治疗。临床乳腺癌，第13卷，第1期，53-60(C)2013爱思唯尔公司，版权所有。
Neoadjuvant anthracycline- and taxane-based chemotherapy for breast carcinoma might result in the decrease of HER2/neu protein expression which can indicate the sensitivity to chemotherapy and might be a predictive marker for pathologic complete response. However, they have the stable gene HER2/neu gene amplification status. Thus, retesting HER2/neu immunohistochemistry (IHC) status in residual tumors after neoadjuvant chemotherapy (NAC) should be considered in order to optimize adjuvant systemic therapy postsurgery.Introduction: Reliably estimating HER2/neu expression in breast cancer is important for predicting patient prognosis and optimizing adjuvant therapeutic strategies. In this retrospective cohort study, effects of NAC on HER2/neu status in invasive breast cancer were evaluated, and the related factors were analyzed. Patients and Methods: One hundred thirty-one patients with primary breast cancer were treated with anthracycline- and/or taxane-based NAC. HER2/neu status was evaluated by IHC on core needle biopsies of primary tumors before NAC and surgical resection specimens of post-NAC residual breast cancers or tumor-positive axillary lymph nodes. Thirty-two pairs of specimens with discordant HER2/neu IHC scores were analyzed by fluorescence in situ hybridization (FISH). Results: A significant difference in HER2/neu status by IHC between core needle biopsies and surgical resection specimens in patients receiving NAC was observed. After NAC, 23.4% (29 of 124) of tumors showed downregulated HER2/neu expression by IHC. Alterations of HER2/neu IHC scores did not significantly correlate with tumor subtype, pathologic response to NAC, adjuvant regimen, or time interval from the last chemotherapy to surgery. HER2/neu protein overexpression level was associated with favorable pathologic response to anthracycline and taxane-based chemotherapy. However, tumors with altered HER2/neu IHC scores after NAG revealed stable HER2/neu gene amplification/nonamplification by FISH analysis. Conclusion: Neoadjuvant chemotherapy for breast carcinoma resulted in the HER2/neu status alteration by IHC, but they have stable gene amplification status by FISH. HER2/neu protein overexpression indicated greater sensitivity to neoadjuvant anthracycline- and taxane-based chemotherapy. Thus, retesting HER2/neu IHC status in residual tumors after NAG should be considered in order to optimize adjuvant systemic therapy. Clinical Breast Cancer, Vol. 13, No. 1, 53-60 (C) 2013 Elsevier Inc. All rights reserved.