Department of Pathology, Zealand University Hospital, Sygehusvej 9, 4000, Roskilde, Denmark.
University of Copenhagen, Blegdamsvej 3B, 2100, Copenhagen, Denmark.
Breast Cancer Res. 2023 Nov 9;25(1):139. doi: 10.1186/s13058-023-01739-9.
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.
鉴于人表皮生长因子受体 2（HER2）低表达的乳腺癌治疗最近取得了进展，我们旨在研究丹麦所有病理科在评估 HER2 低水平乳腺癌方面的实验室间变异性。
我们从丹麦乳腺癌研究组获得了 2007 年至 2019 年间所有诊断为原发性浸润性乳腺癌的女性患者的数据，这些患者随后被分配进行治愈性治疗。
在 50714 例患者中，有 48382 例记录了 HER2 评分和状态，其中 59.2%属于 HER2 低水平组（评分 1+或 2+但无基因扩增），26.8%的 HER2 评分 0，14.0%为 HER2 阳性。病理科之间的 HER2 低水平病例比例范围为 46.3%至 71.8%（P<0.0001），多年来范围为 49.3%至 65.6%（P<0.0001）。相比之下，HER2 阳性率在科室之间的范围为 11.8%至 17.2%（P<0.0001），多年来范围为 12.6%至 15.7%（P=0.005）。在患者数量最多的 8 个科室中，HER2 低水平病例的变异性从 2011 年到 2019 年有所增加，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，检查科室与 HER2 评分 0 和 HER2 阳性均显著相关（P<0.0001），但在前一种情况下，比值比的离散度更大（范围 0.25-1.41 与 0.84-1.27）。
我们的数据显示，HER2 低水平乳腺癌的评估存在高度的实验室间变异性。这些发现使人怀疑目前用于 HER2 的检测方法是否足够稳健和可靠，以在日常临床实践中选择 HER2 低水平患者进行 HER2 靶向治疗。
