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Abstract：
Considering the recent advancements in the treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2), we aimed to examine inter-laboratory variability in the assessment of HER2-low breast cancer across all Danish pathology departments.
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.
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.
摘要：
背景：考虑到人类表皮生长因子受体2（HER2）低表达的乳腺癌治疗的最新进展，我们的目的是研究所有丹麦病理部门在评估HER2水平低的乳腺癌时的实验室间差异.
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。
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。
