Sneige Nour, Hess Kenneth R, Multani Asha S, Gong Yun, Ibrahim Nuhad K
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2017 Apr 1;123(7):1115-1123. doi: 10.1002/cncr.30460. Epub 2016 Nov 28.
The 2013 testing guidelines for determining the human epidermal growth factor receptor 2 (HER2) status include new cutoff points for the HER2/chromosome enumeration probe 17 (CEP17) ratio and the average HER2 copy number per cell, and they recommend using a reflex test with alternative chromosome 17 probes (Ch17Ps) to resolve equivocal HER2 results. This study sought to determine the clinical utility of alternative Ch17Ps in equivocal cases and the effects of equivocal results and/or a change in the HER2 status on patients' outcomes.
The University of Texas MD Anderson Cancer Center database of HER2 dual-probe fluorescence in situ hybridization results from 2000 to 2010 was searched for cases of invasive breast cancer with HER2/CEP17 ratios < 2 and average HER2 copy numbers < 6 per cell. Cases with HER2 copy numbers of 4 to < 6 (the definition of equivocal HER2 results) were analyzed with alternative Ch17Ps for Smith-Magenis syndrome and retinoic acid receptor α genes. Disease-free survival (DFS) and overall survival (OS) were evaluated with respect to the HER2 copy number with multivariate Cox proportional hazards regression.
Among the 3630 patients meeting the inclusion criteria, 137 (4%) had equivocal HER2 results. With alternative Ch17Ps, 35 of 57 equivocal HER2 cases (61%) were upgraded to a positive HER2 status, and 22 cases (39%) remained unchanged. The 5-year DFS and OS adjusted hazard ratios (HRs) for copy numbers of 4 to < 6 versus < 4 were 0.6 (95% confidence interval [CI], 0.3-1.2) and 0.5 (95% CI, 0.2-1.0) with P values of .16 and .66, respectively. In comparison with HER2-negative cases, these CIs indicated that equivocal HER2 results were associated with either a protective effect (HR, < 0.5) or no effect (HR, 1.0).
These findings rule out a significant deleterious effect of equivocal HER2 results. Alternative Ch17Ps may erroneously upgrade the HER2 status; therefore, they cannot be considered reliable in clinical practice. Cancer 2017;123:1115-1123. © 2016 American Cancer Society.
2013年用于确定人表皮生长因子受体2（HER2）状态的检测指南包括HER2/染色体计数探针17（CEP17）比值和每个细胞平均HER2拷贝数的新临界值，并且推荐使用替代的17号染色体探针（Ch17P）进行反射试验以解决HER2结果不明确的情况。本研究旨在确定在结果不明确的病例中替代Ch17P的临床实用性以及结果不明确和/或HER2状态改变对患者预后的影响。
检索德克萨斯大学MD安德森癌症中心2000年至2010年HER2双探针荧光原位杂交结果数据库，查找HER2/CEP17比值<2且每个细胞平均HER2拷贝数<6的浸润性乳腺癌病例。对HER2拷贝数为4至<6（HER2结果不明确的定义）的病例使用针对史密斯-马吉尼斯综合征和视黄酸受体α基因的替代Ch17P进行分析。通过多变量Cox比例风险回归评估无病生存期（DFS）和总生存期（OS）与HER2拷贝数的关系。
在符合纳入标准的3630例患者中，137例（4%）HER2结果不明确。使用替代Ch17P后，57例HER2结果不明确的病例中有35例（61%）HER2状态升级为阳性，22例（39%）保持不变。拷贝数为4至<6与<4相比，5年DFS和OS调整后的风险比（HR）分别为0.6（95%置信区间[CI]，0.3 - 1.2）和0.5（95%CI，0.2 - 1.0），P值分别为0.16和0.66。与HER2阴性病例相比，这些CI表明HER2结果不明确与保护作用（HR，<0.5）或无作用（HR，1.0）相关。
这些发现排除了HER2结果不明确具有显著有害影响的可能性。替代Ch17P可能会错误地提升HER2状态；因此，在临床实践中不能认为它们是可靠的。《癌症》2017年；123：1115 - 1123。©2016美国癌症协会
