Primary 21-Gene Recurrence Score and Disease Outcome in Loco-Regional and Distant Recurrent Breast Cancer Patients

Background: The 21-gene recurrence score (RS) assay has been proven prognostic and predictive for hormone receptor-positive/HER2-negative, node-negative early breast cancer patients. However, whether primary 21-gene RS can predict prognosis in recurrent breast cancer patients remained unknown. Patients and Methods: Consecutive breast cancer patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital between January 2009 and December 2018 were retrospectively analyzed. Patients with available 21-gene RS result for the primary tumor and reporting disease recurrence during follow-up were included. Association of 21-gene RS and overall survival (OS), post-recurrence overall survival (PR-OS), post-recurrence progression-free survival (PR-PFS), and first-line systemic treatment after recurrence were compared among different groups. Results: A total of 74 recurrent patients were included, with 10, 27, 37 patients in the RS <18, 18–30, and ≥ 31 groups, respectively. Recurrent patients with RS ≥ 31 were more likely to receive chemotherapy as their first-line treatment compared to those with RS <31 (P = 0.025). Compared to those with RS <31, patients with RS ≥ 31 had significantly worse OS (P = 0.025), worse PR-OS (P = 0.026), and a trend of inferior PR-PFS (P = 0.106). Multivariate analysis demonstrated that primary ER expression level (OS: P = 0.009; PR-OS: P = 0.017) and histological grade (OS: P = 0.003; PR-OS: P = 0.009), but not primary 21-gene RS (OS: P = 0.706; PR-OS: P = 0.120), were independently associated with worse OS and PR-OS. Conclusions: High primary 21-gene RS tended to be associated with worse disease outcome in loco-regional and distant recurrent breast cancer patients, which could influence the first-line systemic treatment after relapse, warranting further clinical evaluation.