Human Epidermal Growth Factor Receptor 2-Low Breast Cancer: Prevalence Rate and Scoring Concordance Among Pathologists.

Background: Breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) has emerged as a new category benefiting from anti-HER2 therapies. This study evaluated the prevalence of HER2-low expression and concordance of HER2 scoring among pathologists at King Hussein Cancer Center (KHCC) in Jordan.

Objectives: To determine the prevalence of HER2-low breast cancer tumors and evaluate the interpathologist concordance in HER2 scoring using the 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.

Design: This is a retrospective observational study.

Methods: In total, 116 breast cancer samples were randomly selected from routine practice at KHCC. Each tumor was scored for HER2 expression by 3 pathologists independently using the 2018 ASCO/CAP guidelines. Concordance among pathologists was evaluated using Fleiss' kappa and Cohen's weighted kappa statistics.

Results: The original HER2 scoring revealed 7 tumors (6%) as HER2-negative (0 immunohistochemistry [IHC] score), 84 (72.4%) as HER2-low (including tumors with 1+ IHC score or 2+ IHC score with negative fluorescence in situ hybridization [FISH]), 21 (18.1%) as HER2-positive (including tumors with 3+ IHC score or 2+ IHC score with positive FISH), and 4 (3.4%) as equivocal (2+ IHC score with no FISH). Consensus scoring showed 1+ as the most frequent HER2 score. Complete agreement among all 3 pathologists occurred in 78 tumors (67.2%), while high agreement (agreement among 2 pathologists) occurred in 38 tumors (32.8%). Cohen's weighted kappa ranged from 0.691 to 0.849, indicating substantial agreement. The Fleiss kappa of overall agreement on HER2 scoring was 0.645.

Conclusion: This study highlights a significant prevalence of HER2-low tumors among the randomly selected sample of Jordanian breast cancer patients and demonstrates substantial interpathologist agreement in HER2 scoring. These findings underscore the importance of standardized HER2 scoring and the potential impact of emerging therapies on a large patient population in Jordan.