Utilization and Outcomes of the 21‐Gene Recurrence Score in pN2 Breast Cancer Patients

Background/Aim: The 21‑gene assay recurrence score (RS) can guide the use of chemotherapy for the management of patients with pN0‑ 1 [1‑3 positive lymph nodes (LNs)] breast cancer. However, practice patterns based on this assay, as well as associated outcomes, have not been evaluated for patients with pN2 (4‑9 positive LNs) disease. Patients and Methods: The National Cancer Database (NCDB) was queried for patients with newly‑diagnosed, non‑ metastatic, hormone receptor‑positive, Her2‑negative, pN2 breast cancer who underwent adjuvant endocrine therapy and had a known RS. Kaplan–Meier analysis was used to evaluate overall survival (OS); Cox proportional hazards modeling determined variables associated with OS. Results: Of 1,658 patients, 1,109 (67%) received chemotherapy and 549 (33%) did not. Chemotherapy was administered to 54% of patients with a low‑risk recurrence score (RS), 67% with intermediate‑risk RS, and 75% with high‑risk RS. Chemotherapy was associated with improved 5‑year OS in low‑risk RS (95.5% vs. 87.4%), intermediate‑risk RS (91.9% vs. 83.5%), and high‑risk RS (81.3% vs. 50.2%) (p≤0.001 for all). On Cox multivariable analysis, chemotherapy and the RS risk group significantly associated with OS (p<0.05 for both). Qualitatively, patients over 70 years of age appeared to benefit comparatively less from chemotherapy. Conclusion: Despite the underutilization of chemotherapy for hormone receptor‑positive, Her2‑negative, pN2 patients, it was associated with improved OS for all 21‑gene panel risk groups. These results support the existing standard of chemotherapy for this population, although omission could be considered in patients over 70 years of age.