HER2 Status Determined by Central Laboratory Testing May Be More Reliable than Routine Local Testing

Susan Reckling

March 2013, Highlights - Breast Cancer


Determining HER2 status utilizing novel central laboratory testing techniques has been shown to be more reliable than routine local HER2 testing, such as immunohistochemistry or in situ hybridization. This finding for patients with HER2-positive breast cancer may lead to future therapeutic applications for patients with HER2-negative breast cancer as well.

The accurate assessment of tumor HER2 status is critical in determin­­ing appropriate therapy for patients with breast cancer, noted Denise A. Yardley, MD, Senior Investigator of the Breast Cancer Research Program at the Sarah Cannon Research Institute in Nashville, TN, who presented the results of a multicenter retrospective biomarker study.

Dr Yardley’s team compared the HERmark HER2 total protein expression (H2T) cancer assay with local (ie, site-reported) HER2 testing and central laboratory HER2 retesting of formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues.

The HERmark Breast Cancer Assay

The HERmark breast cancer assay is a novel method used to quantitatively measure the levels of HER2 expression (or H2T levels). The quantitative total HER2 measurements by the HERmark assay and the results of local (“real-world”) HER2 testing were correlated with tumor histopathologic characteristics and overall survival (OS) in a cohort of 192 FFPE breast cancer samples from patients, 90% of whom had not received HER2-targeted therapy. The study sites were instructed to identify approximately 50% HER2-positive and 50% HER2-negative breast cancer cases.

Dr Yardley emphasized that high H2T levels (>13.8) that were determined by the HERmark assay significantly correlated with poor OS (hazard ratio [HR], 5.6; P <.001), whereas HER2-positive status that was determined by local testing only trended with OS (HR, 1.78; P = .098). The observed discrepancy in OS based on different HER2 classification methods appeared to be a result of the misclassification of HER2 status as determined by local testing.

Of note, of the 24 triple-negative breast cancer cases that had been reported by local testing, 4 were reclassified as HER2-positive by using the HERmark assay.

The investigators emphasized that the results of this retrospective study confirmed previous reports that HER2 status that is determined by central laboratory testing is more reliable than local testing, real-world HER2 results.

In addition, quantitative H2T levels, determined via the HERmark assay, may enrich the identification of HER2-positive as well as HER2-negative breast cancers and thus may provide added clinical value to real-world local HER2 testing.