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

Abstract

Background: Older breast cancer patients (≥70 years) are under-represented in clinical trials and remain an undertreated population. Gene 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. Patients and methods: Research versions of the genomic grade index (GGI), 70-gene, 21-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 ≥ 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. Models were adjusted for tumour size, grade, ER, lymph node status and hormonal therapy. Recurrence Free Survival (RFS) censored at 10 years was used as the clinical endpoint. Results: All 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 ≤ 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 ≤ 0.05) but only the 70-gene, CCS, ROR-P, and PAM50 signatures remained so in multivariable analysis (Cox proportional hazards, P ≤ 0.05). Conclusions: In general, we found that gene signatures provide prognostic information in survival analyses of all, ER+/LN+ and ER+/LN- older (≥70 years) breast cancer patients, suggesting a potential role in aiding treatment decision in older patients.