The Impact of Post-Mastectomy Chest-Wall Radiation on Overall Survival for Intermediate-Risk Breast Cancer Patients: A National Cancer Data Base Analysis

Abstract

The recommendation of post-mastectomy radiation therapy (PMRT) to breast cancer women with intermediate risk disease still requires a great deal of clinical judgment without a single, validated formula. We aimed to assess the impact of PMRT on overall survival (OS) among patients with breast cancer considered intermediate risk for local recurrence by querying the National Cancer Data Base (NCDB) 2004-2014 for breast cancer. We replicated the SUPREMO phase III clinical trial by including patients (age >=18) with pT1-2N1 (or pT2N0 with either histologic Grade = 3 or presence of LVI) who underwent total mastectomy and did not receive neoadjuvant therapy. PMRT had a total radiation dose 40-70 Gy and was given within 6 months after surgery. OS was defined as months from the date of surgery. Logistic regression was applied to assess the pattern of PMRT utilization. Cox proportional hazard model was used for the association with OS. Propensity score (PS) overlap weighting was implemented to balance all observed baseline characteristics and to eliminate the selection bias. The effect of PMRT in the subgroups was estimated through the multivariable model (MVA) with interactions. We obtained 35,244 eligible subjects with a median follow up of 65.5 months. The median age was 57, 82.6% were white, 55.6% had 1 positive lymph node (PLN), 43.7% of tumors were pT1, the median tumor size was 2.2 cm, 38.4% had Grade III-IV, 96.2% had a negative surgical margin, and 68.3% received adjuvant chemotherapy. 4841 (13.7%) received PMRT while 30,403 (86.3%) received no radiation (NR). There was a clearly increasing trend of PMRT utilization over the years. In MVA by logistic regression, the factors associated with a higher probability of PMRT usage include PLN =2-3, present of LVI, pT2, and younger age. The 10-year survival rate was 72.1% (PMRT) vs. 68.7% (NR) by KM method. In MVA with OS by controlling for baseline demographic and disease characteristics, the hazard ratio (HR) for PMRT vs. NR was 0.81 (95%CI: 0.74-0.89), and it was 0.84 (95%CI: 0.74-0.95) by the PS weighting approach. In the subgroups, the HR was 0.75 (95%CI: 0.64-0.88) among patients with PLN = 3, 0.69 (95%CI: 0.59-0.81) among women not receiving adjuvant chemotherapy, 0.68 (95%CI: 0.60-0.77) among women with age > 60, and 0.72 (95%CI: 0.58-0.90) among patients whose tumors exhibited LVI. In this large retrospective study based on NCDB, on average, PMRT provided significant long-term survival benefit among intermediate risk breast cancer patients, with a larger survival benefits noted amongst patients with 3 PLN, age > 60, or the presence of LVI. More informative guidance for the utilization of PMRT may require additional information such as disease specific survival or recurrence (which is unavailable in NCDB), and we are looking forward to the results from the SUPREMO trial.