Clinically relevant gene signatures provide independent prognostic information in older breast cancer patients

PurposeGene signatures have been shown to add prognostic information beyond that of routine clinico-pathological factors, however their utility in older breast cancer patients remains unclear. As such, the aim of this study was to determine if gene signatures can provide prognostic information that may aid treatment decisions for older breast cancer patients. Experimental designResearch versions of the genomic grade index (GGI), 70-gene recurrence score (RS), cell cycle score (CCS), PAM50 Risk of Recurrence score - Proliferation (ROR-P), and PAM50 signatures were applied to 39 breast cancer datasets totalling 9583 patients. After filtering based on age [&ge;] 70 years, the presence of Estrogen Receptor (ER) and survival information availability 871 patients remained. The prognostic capacity of signatures was tested in all (n=871), ER-positive/lymph node-positive (ER+/LN+, n=335) and ER-positive/lymph node-negative (ER+/LN-, n=374) patients using Kaplan-Meier and multivariable Cox proportional hazard modeling. ResultsAll gene signatures were statistically significant in Kaplan-Meier analysis of all and ER+/LN+ patients (Log-rank P < 0.001). This significance remained in multivariable analysis (Cox proportional hazards, P [&le;] 0.05). In ER+/LN-patients the GGI, 70-gene, CCS, ROR-P, and PAM50 signatures were significant in Kaplan-Meier analysis (Log-rank P [&le;] 0.05) but only the 70-gene, CCS, ROR-P, and PAM50 signatures remained so in multivariable analysis (Cox proportional hazards, P [&le;] 0.05). ConclusionsIn general, we found that gene signatures provide prognostic information in survival analyses of all, ER+/LN+ and ER+/LN-older ([&ge;]70 years) breast cancer patients, suggesting a potential role in aiding treatment decision in older patients. Translational RelevanceThe utility of gene expression signatures in breast cancer patients has been most clearly demonstrated in the TAILORx, RxPONDER and MINDACT randomised clinical trials. However, few older patients ([&ge;]70 years) were included in these trials meaning that signature utility in this patient group remains unclear. As such, we performed the first comprehensive study comparing the prognostic performance of multiple clinically relevant gene expression signatures in a single older breast cancer patient cohort. We show that in general gene signatures provide independent prognostic information in All, ER+/LN+ and ER+/LN-patients who are over the age of 70 years. These results support a potential role for signatures in aiding treatment decisions in older breast cancer patients and indicate that further investigation is warranted in prospective clinical study to elucidate their treatment predictive value.