TY - JOUR

T1 - High inter-laboratory variability in the assessment of HER2-low breast cancer

T2 - a national registry study on 50,714 Danish patients

AU - Nielsen, Kåre

AU - Sode, Michael

AU - Jensen, Maj-Britt

AU - Berg, Tobias

AU - Knoop, Ann

AU - Ejlertsen, Bent

AU - Lænkholm, Anne-Vibeke

N1 - Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - Background: 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. Methods: 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. Results: 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). Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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). Conclusions: 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.

KW - Breast cancer

KW - HER2 low

KW - Human epidermal growth factor receptor 2 (HER2)

KW - Immunohistochemistry

KW - Reproducibility

KW - Variability

U2 - 10.1186/s13058-023-01739-9

DO - 10.1186/s13058-023-01739-9

M3 - Journal article

C2 - 37946261

AN - SCOPUS:85176091927

VL - 25

JO - Breast Cancer Research

JF - Breast Cancer Research

SN - 1465-5411

M1 - 139

ER -