Oncotype Score as a Predictor of Local-Regional Recurrence in Early Stage Breast Cancer (BC)

Abstract

Local-regional therapy in BC is largely guided by clinico-pathologic features, whereas molecular biology and intrinsic gene signatures of the cancer are used to prescribe risk-tailored systemic therapy. The objective of this study was to evaluate the incidence of local-regional relapse in early stage BC. Further, to evaluate the correlation of Oncotype Dx score, in addition to the clinico-pathologic features with risk of relapse. This was an institutional review board approved retrospective study from our institutional database. We identified 1355 patients with ER+ Stage I and II BC who had undergone Oncotype Dx testing. For this study, we included only those patients with unilateral BC and minimum follow-up of 2 years (n = 792). Patients were treated with mastectomy, or lumpectomy and radiation (RT) + systemic therapy at the discretion of treating physician. We scored patients based on the first site of failure: local-regional relapse (LRR) only, distant metastases (DM) only, and both (LRR+DM). The association between clinical covariates (Age: ≥50, <50; T-size: ≤2 cm, >2 cm; Grade), Oncotype Dx score (<18, ≥18), local treatment (mastectomy vs. lumpectomy/RT), and failure events was evaluated by univariable and multivariable Cox proportional hazards models. Survival was estimated using the Kaplan-Meier and log-rank test method. Among 792 patients that met the study criteria, 73.5% (n = 582) underwent lumpectomy/RT and 26.5% (n = 210) were treated with mastectomy. Systemic therapy was administered in 50% of patients. Majority (81%) had T-size ≤2 cm. Median age was 56 years (range, 25-84 years), and median follow-up was 55 months (range 24-137 months). Five-year OS was 99.1% (95% CI = 97.9-99.6%) and 5-year DFS was 93.8% (95% CI = 91.3-95.6%). The incidence of LRR was 2.2%, DM was 2.6%, and LRR+DM was 0.25% of patients. On univariable analysis, the risk of LRR was significantly associated T-size >2 cm, and Oncotype Dx score ≥18. The factors significantly associated with risk for DM were T-size > 2 cm, grade 2/3, and Oncotype Dx score ≥18. On multivariable analysis both T-size> 2 cm, and Oncotype Dx score >18 remained significant risk factors for LRR and DM (Table 1). Both factors also remained significant upon subset analysis of patients treated with lumpectomy/RT + systemic therapy.Tabled 1Abstract 116; Table 1 Factors Influencing LRR and DM on multivariate analysisRisk FactorsLocal-regional relapseHazard RatioDistant MetastasisHazard RatioT-size >2 cm2.77 (95% CI = 1.07-7.15; P = 0.034)*6.7 (95% CI 2.8-16.3; P<0.0001)*Oncotype Score ≥182.8 (95% CI = 1.08-7.36; P = 0.03)*5.2 (95% CI 1.7-15.5; P = 0.003)* Open table in a new tab Our study suggests that in addition to clinicopathologic variables Oncotype Dx score may provide useful information regarding risk of LRR. Further research is needed to establish a role for molecular and gene profiles in providing risk-tailored delivery of radiation.