IMPAKT 2015 News: Analysis of Large Dataset Shows Improved Concordance of Local and Central HER2 Status

Decreasing discordance rates between central and local HER2

Clinical evaluation of HER2 status is getting better in Germany, as demonstrated by a decline in discordance rates between central and local HER2 status, according to Berit Pfitzner, Charité Universitätsmedizin Berlin, Germany who presented findings on behalf of the German Breast Group. Results from a large analysis were detailed in a poster exhibited during the Biomarkers in Breast Cancer poster session at the IMPAKT Breast Cancer Conference held 7-9 May, 2015 in Brussels, Belgium.

Human epidermal growth factor receptor 2 (HER2; also known as EGFR-related 2, ERBB2) represents a therapeutic target for the most frequently diagnosed cancer in females during 2014.

Amplification and overexpression of the ERBB2 gene occurs in approximately 18 to 25% of invasive human breast cancers and tumours with this genotype are known to exhibit a more aggressive behavior. For this reason and because several antibodies targeting HER2 have been developed and clinically used, the determination of HER2 status is quite important.

Prof. Pfitzner and colleagues compared the central and local HER2 status of patients with primary breast cancer participating in five large neoadjuvant, multicentre studies to determine whether the rate of discordance between central and locally tested HER2 status had decreased over the past years.

Increased use of quality control measures may parallel a decline in discordance rates

The investigators evaluated data from 1597 patients with HER2 positive cancers participating in the Gepar-Trio, Quatro, Quinto, Sixto and Septo trials between 2001 and 2013.

They found the discordance rate decreased from the earliest to most recent trials, from 52.4% in the GeparTrio trial to 8.4% in the GeparSepto trial. Discordance rates for the other trials showed a steady decline; the discordance rate was 25.4% in GeparQuattro, 22.7% in GeparQuinto, and 7.0% in the GeparSixto trials.

Regarding the 62.6% of patients with hormone receptor positive, HER2 positive tumours, the HER2 discordance rates were 58.8%, 30.8%, 29.2%, 0%, and 9.2% in the Gepar Trio, Quattro, Quinto, Sixto and Septo trials, respectively.

The discordance rate for the 37.4% of patients with hormone receptor negative, HER2 positive tumours also showed a linear decrease, except in the GeparSixto trial wherein the discordance rate was 16.3%. The rate in the other trials was highest in GeparTrio at 37.9% and decreased steadily to 18.9% in GeparQuattro, 13.9% in GeparQuinto and finally to 6.1% in GeparSepto.


Findings from this analysis of a very large dataset from five neoadjuvant breast cancer studies show a steady decrease in the discordance rate comparing the central and locally tested HER2 status.

The investigators suggest that these results are co-incident with the implementation of ring tests and other quality control measures for HER2-testing in Germany.


58P Concordance of local and central HER2 status in 1597 patients participating in German neoadjuvant breast cancer studies