From the Danish Breast Cancer Group, we obtained data on all women diagnosed with primary invasive breast cancer in 2007-2019 who were subsequently assigned for curatively intended treatment.
Of 50,714 patients, HER2 score and status were recorded for 48,382, among whom 59.2% belonged to the HER2-low group (score 1+ or 2+ without gene amplification), 26.8% had a HER2 score of 0, and 14.0% were HER2 positive. The proportion of HER2-low cases ranged from 46.3 to 71.8% among pathology departments (P < 0.0001) and from 49.3 to 65.6% over the years (P < 0.0001). In comparison, HER2 positivity rates ranged from 11.8 to 17.2% among departments (P < 0.0001) and from 12.6 to 15.7% over the years (P = 0.005). In the eight departments with the highest number of patients, variability in HER2-low cases increased from 2011 to 2019, although the same immunohistochemical assay was used. By multivariable logistic regression, the examining department was significantly related to both HER2 score 0 and HER2 positivity (P < 0.0001) but showed greater dispersion in odds ratios in the former case (range 0.25-1.41 vs. 0.84-1.27).
Our data showed high inter-laboratory variability in the assessment of HER2-low breast cancer. The findings cast doubt on whether the current test method for HER2 is robust and reliable enough to select HER2-low patients for HER2-targeted treatment in daily clinical practice.
方法:来自丹麦乳腺癌组织,我们获得了2007-2019年被诊断为原发性浸润性乳腺癌的所有女性的数据,这些女性随后被分配进行治疗计划.
结果:在50,714名患者中,记录的HER2评分和状态为48,382,其中59.2%属于HER2低组(评分1或2无基因扩增),26.8%的HER2评分为0,14.0%的HER2阳性。在病理部门中,HER2低病例的比例为46.3%至71.8%(P<0.0001),多年来为49.3%至65.6%(P<0.0001)。相比之下,部门的HER2阳性率为11.8%至17.2%(P<0.0001),多年来为12.6%至15.7%(P=0.005)。在病人最多的八个科室,从2011年到2019年,低HER2病例的变异性增加,尽管使用了相同的免疫组织化学检测方法.通过多变量逻辑回归,检查部门与HER2评分0和HER2阳性显着相关(P<0.0001),但在前一种情况下显示出更大的优势比分散(范围为0.25-1.41vs.0.84-1.27)。
结论:我们的数据显示,低HER2乳腺癌评估的实验室间差异很大。这些发现使人们怀疑,目前的HER2测试方法是否足够稳健和可靠,足以在日常临床实践中选择低HER2患者进行HER2靶向治疗。