Identifying High-Risk N0 and N1 Breast Cancer Patients for Postmastectomy Radiation Therapy by an 18-Gene Classifier

Abstract

The definition of high-risk N0 and N1 breast cancer patients, who would benefit from regional node irradiation (RNI) or post-mastectomy radiotherapy (PMRT), is still no consensus. This study aims to identify the high-risk N0 and N1 mastectomy patients by an 18-gene panel. The high-risk patients would benefit from adjuvant radiotherapy. Three hundred fifty-nine (359) breast cancer patients who had microarray study for mRNA on the primary tumor tissues were chosen for this study. Eligible patients should have (1) an invasive breast cancer, (2) a mastectomy as first treatment, (3) pathology stages of T1-2N0 or T1-2N1, (4) frozen fresh tissues available and (5) an informed consent. Patients with N3, T4, or M1 disease were excluded in this analysis. Using pre-set cutoff of each gene and 18-gene scoring algorithm, we define scores of ≥ 44 as the high-risk group of locoregional recurrence (LRR) and scores of <21 as the low risk group of distant metastasis. This new 18-gene classifier identified 12% (24/200) of N0 patients and 26.4% (42/159) of N1 patients to be the high risk of LRR. The 5-year LRR-free probability, relapse-free probability, and overall survival for N0 patients were 82.8% (95% CI = 60.3 -93.2%), 62.2% (39.9-78.3%) and 69.8% (46.9-84.3%), respectively. The 5-year LRR-free probability, relapse-free probability, and overall survival for N1 patients were 72.2% (53.8-84.3%), 67.1% (48.7-80.2%), and 66.9% (46.2-81.1%), respectively. Among high-risk N0-N1 patients, PMRT reduced the 5-year probability of LRR from 33.1% to 17.2% (P = 0.09), and decreased the probability of any recurrence from 50.0% to 22.5% (P = 0.012). Multivariate analysis indicated that the 18-gene classifier with scores of ≥44 is independently associated with any recurrence in N0 and N1 mastectomy patients; the hazard ratio is 4.4 (2.4-8.1). N0 and N1 breast cancer patients with 18-gene scores of ≥44 would benefit from PMRT significantly by this study. The 18-gene classifier could identify the high-risk LRR patients for PMRT. More broad validation in other institutes is in underway.