Measurement of hormone receptors, HER2 and Ki-67 is prognostic for breast cancer (BC) outcome and prediction of therapy response. The Xpert® Breast Cancer STRAT4 based on RT-qPCR, is used to classify BC tissues regarding their hormone receptor status, HER2 and proliferation via Ki-67. This study compares the mRNA expression analysis of ER, PR, HER2, and Ki-67 in a large clinical trial cohort by an automated in-vitro diagnostic platform and central IHC.
Breast cancer patients from the prospective GBG multicenter trial GeparX (NCT02682693) (still recruiting) were included in this biomarker project. We used formalin-fixed paraffin embedded (FFPE) pretherapeutical core biopsies with a tumor content >10%. A 4µm FFPE tissue section was first processed with the Xpert® FFPE Lysis Kit, the sample lysate was placed in the GeneXpert® cartridge system in which the purification, amplification and real-time detection of the gene expression of ER, PR, HER2 and Ki-67 took place automatically.
Of 503 samples with valid mRNA measurements, 258 samples (51,3%) were ER-positive, 196 (39%) PR-positive, 78 (15,5%) HER- positive and 421 (83.7%) were Ki-67-high (>20%). The simple kappa coefficient was for ER = 0.7938, PR = 0.6540, HER2=0.8172 and Ki-67=0.3655. This implies that the ER, PR and HER2 measurements show a high correlation between both methods, whereas the Ki-67 measurement does not. The accuracy between the STRAT4 and IHC was 89.7% for ER, 83.3% for PR, 94.6% for HER2 and 86.7% for Ki-67.
Our results show a high concordance between standardized central IHC and automated mRNA expression analysis for the most important BC biomarkers ER, PR and HER2. For the continuous proliferation marker Ki-67, the concordance is slightly lower. The STRAT4 assay might offer an additional option to conventional methods for BC biomarker assessment, in particular in situations where ICH is not feasible. To determine the clinical validity, additional outcome analyses are necessary.
GeparX NCT02682693.
GBG Forschungs GmbH.
The clinical trial was supported by Celgene and Amgen and this study by Cepheid.
All authors have declared no conflicts of interest.