Impact of Different Modules of 21-Gene Assay in Early Breast Cancer Patients

Abstract Background: Young patients were under-evaluated in the construction and validation of the 21-gene Assay Recurrence Score (RS). Previous evidence suggested that RS performed differently according the ages of patients. Our study aimed to explore the molecular driving patterns in patients of different ages.Methods: A total of 1,078 estrogen receptor (ER)-positive breast cancer patients between Jan 2009 and Mar 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were divided into three subgroups: Group A, ≤40y and premenopausal (n=97); Group B, >40y and premenopausal (n=284); Group C, postmenopausal (n=697). The correlation of RS and its modules and the variance of RS modules was explored.Results: Estrogen module had a stronger correlation with RS in patients >40y (ρ = -0.76 in Group B and -0.79 in Group C) compared with patients ≤40y (ρ = -0.64). Contrarily, the correlation between RS and invasion group was weaker in patients >40y (ρ = 0.29 in Group B and 0.25 in Group C) than in patients ≤40y (ρ = 0.44). The proliferation module contributed most to the variance in young patients (37.3%) while ER module contributed most in old patients (54.1% in Group B and 53.4% in Group C). For RS >25, proliferation module was the leading driver in all three subgroups (ρ = 0.38, 0.53 and 0.52 in Group A, B and C) while estrogen module had a weaker association with RS. The negative impact of ER related features on RS was stronger in clinical low-risk patients while the positive effect of proliferation module was stronger in clinical high-risk patients.Conclusions: RS was primarily driven by estrogen module in patients regardless of age, but the proliferation module had a stronger impact on RS in patients ≤40y than in those >40y. The impact of modules varied in patients with different genetic and clinical risk.