Loss of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Metastatic Sites of HER2-Overexpressing Primary Breast Tumors
Loss of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Metastatic Sites of HER2-Overexpressing Primary Breast Tumors
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DOI：
10.1200/jco.2010.33.8889
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发表时间：
2012-02-20
影响因子：
45.3
通讯作者：
Ueno, Naoto T.
中科院分区：
文献类型：
--
作者：
Niikura, Naoki;Liu, Jun;Ueno, Naoto T.
目的评价人表皮生长因子受体2(HER2)阳性的乳腺癌患者是否存在HER2阳性(一致性)或HER2阴性(不一致性)的转移性肿瘤。然后，我们评估转移灶活检前使用曲妥珠单抗或化疗是否对HER2不一致性有任何影响。我们还比较了HER2整合和不整合肿瘤患者的总体生存时间。患者和方法我们回顾了1997-2008年间在MD Anderson癌症中心首次诊断为HER2阳性(免疫组织化学3+和/或荧光原位杂交阳性)且有可供复查的转移瘤活检结果的所有患者。在182例HER2阳性的原发肿瘤患者中，有43例(24%)HER2阴性转移瘤。HER2不符合率在患者是否接受化疗的基础上有显著差异(P=.022)，但在患者是否接受曲妥珠单抗的基础上没有显著差异(P=.296)。HER2状态不协调的患者的总存活率比HER2状态一致的患者短(风险比[HR]，0.43；P=0.003)。67名接受曲妥珠单抗治疗的患者(HR，0.56；P=.083)和101名未接受曲妥珠单抗治疗的患者(HR，0.53；P=.033)在转移活检前的存活率存在差异。结论我们证实，HER2阳性乳腺癌患者在转移肿瘤中可以发生HER2阳性状态的丧失。我们的数据有力地支持了对转移性病变进行活检以准确确定患者预后和适当使用靶向治疗的必要性。J Clin Oncol30：593-599。(C)2011年美国临床肿瘤学会
PurposeWe evaluated whether patients with human epidermal growth factor receptor 2 (HER2) -positive primary breast tumors had metastatic tumors that were HER2 positive (concordant) or HER2 negative (discordant). We then evaluated whether treatment with trastuzumab or chemotherapy before biopsy of the metastasis had any effect on the rate of HER2 discordance. We also compared the overall survival durations of patients with HER2-concordant and -discordant tumors.Patients and MethodsWe retrospectively identified all patients who initially had been diagnosed with HER2-positive (immunohistochemistry 3+ and/or fluorescent in situ hybridization positive) primary breast cancer between 1997 and 2008 at MD Anderson Cancer Center who also had metastatic tumor biopsy results available for review.ResultsWe included 182 patients who met our criteria. Forty-three (24%) of the 182 patients with HER2-positive primary tumors had HER2-negative metastatic tumors. The HER2 discordance rates differed significantly on the basis of whether patients received chemotherapy (P = .022) but not on the basis of whether patients received trastuzumab (P = .296). Patients with discordant HER2 status had shorter overall survival than did patients with concordant HER2 status (hazard ratio [HR], 0.43; P = .003). A survival difference remained among the 67 patients who received trastuzumab (HR, 0.56; P = .083) and 101 patients who did not (HR, 0.53; P = .033) before their metastasis biopsies.ConclusionWe confirmed that loss of HER2-positive status in metastatic tumors can occur in patients with primary HER2-positive breast cancer. Our data strongly support the need for biopsies of metastatic lesions to accurately determine patient prognosis and appropriate use of targeted therapy. J Clin Oncol 30:593-599. (c) 2011 by American Society of Clinical Oncology