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

Abstract BACKGROUND The 21-gene assay (Oncotype DX®) can be used to guide use of chemotherapy in the management of patients with pN1 [1–3 positive lymph nodes (LNs)] breast cancer, specifically with respect to assessing potential benefit of chemotherapy. However, practice patterns based on this assay, as well as associated outcomes, have not been prospectively evaluated for pN2 (4–9 positive LNs) disease. METHODS The National Cancer Database (NCDB) was queried for women with newly-diagnosed, non-metastatic, hormone receptor-positive, Her2-negative, pN2 breast cancer who underwent adjuvant endocrine therapy. Kaplan-Meier analysis evaluated 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% for intermediate-risk RS, and 75% for high-risk RS. The median follow-up was 49.9 months (interquartile range, 33.6–71.2 months). 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). Further subset analysis revealed that the benefit of chemotherapy was independent of the RS, LN ratio, and the extent of LN dissection. Qualitatively, patients over 70 years of age appeared to benefit comparatively less from chemotherapy. CONCLUSIONS 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 its omission could be considered in patients over 70 years of age.