Assessing the Discordance Rate Between Local and Central HER2 Testing in Women With Locally Determined HER2-Negative Breast Cancer

BACKGROUND: The importance of human epidermal growth factor receptor 2 (HER2) as a prognostic and predictive marker in inva-sive breast cancer is well established. Accurate assessment of HER2 status is essential to determine optimal treatment options. METHODS: Breast cancer tumor tissue samples from the VIRGO observational cohort tissue substudy that were locally HER2-negative were retested centrally with both US Food and Drug Administration (FDA)-approved immunohistochemistry (IHC) and fluo-rescence in situ hybridization (FISH) assays, using FDA-approved assay cutoffs; results were compared. RESULTS: Of the 552 unique patient samples centrally retested with local HER2-negative results recorded, tumor samples from 22 (4.0%) patients were deter-mined to be HER2-positive (95 % confidence interval [CI]52.5%-5.7%). Of these, 18 had been tested locally by only one testing meth-odology; 15 of 18 were HER2-positive after the central retesting, based on the testing methodology not performed locally. Compared with the 530 patients with centrally confirmed HER2-negative tumors, the 22 patients with centrally determined HER2-positive tumors were younger (median age 56.5 versus 60.0 years) and more likely to have ER/PR-negative tumors (27.3 % versus 22.3%). These patients also had shorter median progression-free survival (6.4 months [95 % CI53.8-15.9 months] versus 9.1 months [95% CI58.3-10.3 months]) and overall survival (25.9 months [95 % CI5 13.8-not estimable] versus 27.9 months [95 % CI525.0-32.9 months]). CONCLUSIONS: This study highlights the limitations of employing just one HER2 testing methodology in current clinical practice. It identifies a cohort of patients who did not receive potentially efficacious therapy because their tumor HER2-positivity was not determined by the test initially used. Because of inherent limitations in testing methodologies, it is inadvisable to rely on a singl