Evaluation and comparison of different breast cancer prognosis scores based on gene expression data

Background: Breast cancer is one of the three most common cancers worldwide and is the most common malignancy in women. Treatment approaches for breast cancer are diverse and varied. Clinicians must balance risks and benefits when deciding treatments, and models have been developed to support this decision-making. Genomic risk scores (GRS) may offer greater clinical value than standard clinicopathological models, but there is limited evidence as to whether these models perform better than the current clinical standard of care. Methods: : PREDICT and GRSs were adapted using data from the original papers and modification of the genefu R package. Univariable Cox proportional hazards models were produced with BCSS as the outcome. Independent predictors of BCSS were used to build multivariable models with PREDICT. Signatures which provided independent prognostic information in multivariable models were incorporated into the PREDICT algorithm, and assessed for calibration, discrimination and reclassification. Results: : Oncotype DX (ODx), EndoPredict, MammaPrint and Prosigna were univariable predictors of BCSS. ODx and MammaPrint demonstrated prognostic power independent of PREDICT in multivariable models for ER-positive patients; no score predicted BCSS in ER-negative patients. Incorporating these models into PREDICT had only a modest impact upon calibration (with absolute improvements of 0.3-0.8%), discrimination (with no statistically significant c -index improvements) and reclassification (with 6-9% of patients being reclassified). Conclusion: Addition of GRSs to PREDICT had limited impact on model fit or treatment received. This analysis does not support widespread adoption of current GRSs based on our implementations of commercial products.