Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer
Phosphorylated/activated HER2 as a marker of clinical resistance to single agent taxane chemotherapy for metastatic breast cancer
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DOI：
10.1080/07357900500201301
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发表时间：
2005-01-01
影响因子：
2.4
通讯作者：
Seidman, AD
中科院分区：
文献类型：
--
作者：
Modi, S;DiGiovanna, MP;Seidman, AD
目的。确定转移性乳腺癌（MBC）患者磷酸化/活化HER2 （P-HER2）与紫杉烷化疗反应的关系。材料与方法。应用PN2A单克隆抗体，对接受紫杉烷单药治疗的MBC患者存档的肿瘤标本进行免疫组化（IHC）分析，检测其是否存在磷酸化的HER2。采用卡方分析评价P-HER2状态与单药紫杉烷治疗疗效的相关性。结果。126例被确定为可评估免疫组化和临床结果。12例（10%）P-HER2阳性，其中5例有临床进展，7例有紫杉烷治疗的临床获益。在114例P-HER2阴性病例中，20例出现进展，94例有临床获益。chi(2)=3.9724, p = 0.046， p - her2的表达与紫杉烷类药物耐药有显著相关性。结论。磷酸化/活化的HER2与MBC单药紫杉烷治疗的临床耐药有关。pn2a阳性肿瘤患者（42%）与pn2a阴性肿瘤患者（18%,p = 0.046）相比，紫杉烷直接导致疾病进展的可能性更大。HER2状态的功能评估可以提供传统评估所没有的独特预测信息。
Purpose. To determine the association of phosphorylated/activated HER2 (P-HER2) and response to taxane chemotherapy in patients with metastatic breast cancer (MBC). Materials and Methods. Archived tumor specimens of patients with MBC treated on clinical trials with taxane monotherapy were analyzed by immunohistochemistry (IHC) for the presence of phosphorylated HER2 using the PN2A monoclonal antibody. Chi-squared analysis was performed to evaluate the association of P-HER2 status and efficacy of single agent taxane therapy. Results. One hundred twenty-six cases were identified as evaluable for both IHC and clinical outcome. Twelve cases (10 percent) were positive for P-HER2, of which 5 had evidence of clinical progression and 7 had evidence of clinical benefit with taxane therapy. Of the 114 cases that were negative for P-HER2, 20 demonstrated progression and 94 had clinical benefit. Chi-squared analysis revealed a significant correlation between the presence of P-HER2 and resistance to taxane therapy, chi(2)=3.9724 and p = 0.046. Conclusions. Phosphorylated/activated HER2 is associated with clinical resistance to single agent taxane therapy for MBC. The likelihood of direct progression of disease on taxane was greater in cases of PN2A-positive tumors (42 percent) as opposed to PN2A-negative ones (18 percent, p = 0.046). Functional assessment of HER2 status may provide unique predictive information not seen with conventional assessments.