Even low-level HER2 expression may be associated with worse outcome in node-positive breast cancer.
Even low-level HER2 expression may be associated with worse outcome in node-positive breast cancer.
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DOI：
10.1097/pas.0b013e31819437f9
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发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
Buchholz TA
中科院分区：
文献类型：
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作者：
Gilcrease MZ;Woodward WA;Nicolas MM;Corley LJ;Fuller GN;Esteva FJ;Tucker SL;Buchholz TA
HER2是乳腺癌患者对曲妥珠单抗和拉帕替尼反应的重要预测标志物。它也是淋巴结阳性患者的有力预后标志物。虽然标准化检测用于帮助选择抗HER2治疗的患者，但没有标准化标准来评估HER2作为预后标志物。最近使用定量图像分析的数据表明，高和低HER2表达均与不良临床结局相关。使用美国病理学家学会和美国临床肿瘤学会目前推荐的免疫组化评分标准来帮助选择曲妥珠单抗治疗的患者，我们评估了91例淋巴结阳性浸润性乳腺癌患者的肿瘤组织微阵列中HER2蛋白表达，这些患者接受了乳房切除术和基于阿霉素的化疗，未使用曲妥珠单抗，未接受放疗，中位随访时间为12.5年。原发性肿瘤中HER 2的广泛表达（HER 2 ≥ 1 +）与局部区域无复发生存期下降（P = 0.014）、疾病特异性生存期下降（P = 0.001）和总生存期下降（P = 0.001）显着相关。即使在美国病理学家学会和美国临床肿瘤学会现行指南认为HER2阴性的亚组中，在该患者队列中，HER2 = 1 +与HER2 = 0的结局更差相关。在激素受体阳性患者亚组中，HER2 ≥ 1 +与不良结局之间的相关性具有最大的统计学意义。这些发现支持低水平HER2表达可能具有显著临床意义的假设。虽然评估HER2表达对于预测抗HER2治疗的反应最为重要，但检测低水平HER2表达也可能有助于为不适合抗HER2治疗的患者选择更具侵略性的治疗方案。
HER2 is an important predictive marker for response to trastuzumab and lapatinib in breast cancer. It is also a powerful prognostic marker in node-positive patients. Although standardized assays are used to help select patients for anti-HER2 therapy, there are no standardized criteria for assessing HER2 as a prognostic marker. Recent data using quantitative image analysis suggest that both high and low HER2 expression are associated with poor clinical outcome. Using the immunohistochemical scoring criteria currently recommended by the College of American Pathologists and American Society of Clinical Oncology to help select patients for trastuzumab, we evaluated HER2 protein expression in tumor tissue microarrays of 91 node-positive patients with invasive breast carcinoma treated with mastectomy and doxorubicin-based chemotherapy without trastuzumab and without irradiation with a median follow-up of 12.5 years. A wide range of HER2 expression (HER2 ≥ 1 +) in the primary tumor was significantly associated with decreased locoregional recurrence-free survival (P = 0.014), decreased disease-specific survival (P = 0.001), and decreased overall survival (P = 0.001). Even in the subset considered HER2 negative by current College of American Pathologists and American Society of Clinical Oncology guidelines, HER2 = 1 + was associated with worse outcome than HER2 = 0 in this patient cohort. The association between HER2 ≥ 1 + and worse outcome had the greatest statistical significance in the hormone receptor-positive subset of patients. These findings support the hypothesis that low-level HER2 expression may have significant clinical implications. Although the assessment of HER2 expression is most important for predicting response to anti-HER2 therapy, detection of low-level HER2 expression might also be useful in helping to select a more aggressive treatment regimen for patients ineligible for anti-HER2 therapy.