Improvement of the clinical applicability of the Genomic Grade Index through a qRT-PCR test performed on frozen and formalin-fixed paraffin-embedded tissues

The accuracy and concordance of the PCR-GGI with the GGI was assessed using BC patients for which frozen and FFPE tissues as well as microarray data were available (n = 19). The evaluation of the prognostic value of the PCR-GGI was assessed on FFPE material using a consecutive series of 212 systemically treated early BC patients. The predictive performance for tamoxifen benefit was assessed using two ER+ BC populations treated either with adjuvant tamoxifen only (n = 77+139) or first-line tamoxifen for advanced disease (n = 270).The PCR-GGI is based on the expression of 8 genes (4 representative of the GGI and 4 reference genes). A significant correlation was observed between the microarray-derived GGI and the qRT-PCR assay using frozen (ρ = 0.95, p < 10E-06) and FFPE material (ρ = 0.89, p < 10E-06). The prognostic performance of the PCR-GGI was confirmed on FFPE samples (HRunivar. = 1.89; [95CI:1.01-3.54], p = 0.05). The PCR-GGI further identified two subgroups of patients with statistically different time to distant metastasis free survival (DMFS) across the two cohorts of ER+ BC patients treated with adjuvant tamoxifen. Additionally, the PCR-GGI was associated with response to tamoxifen in the advanced setting (HRunivar. = 1.98; [95CI:1.51-2.59], p = 6.9E-07).PCR-GGI recapitulates in an accurate and reproducible manner the performances of the GGI using frozen and FFPE samples.Gene expression profiling has resulted in paradigm shift in the way that researchers and clinical investigators view breast cancer (BC) biology. During the last years, several groups have evaluated the potential of gene expression profiles to improve BC prognostication. This has resulted in the identification of several gene signatures, most of them outperforming current clinico-pathological parameters in predicting clinical outcome (reviewed in [1]).One example is the genomic grade index (GGI) developed by our group [2]. The hypothesis beyond the development of this index was to improve BC