Impact of Post-Mastectomy Radiation Therapy (PMRT) in Women with T1-2N1M0 Breast Cancer: A Multi-Institutional Analysis

Abstract

To investigate the effect of PMRT in women with pT1-2N1M0 breast cancer in the modern era. Data from 5 North American institutions were pooled to include women who underwent mastectomy without neoadjuvant therapy, with pT1-2N1M0 disease from 1995-2015. Patients were divided into discovery and validation cohorts. Missing covariate values were imputed using multiple imputation with chain equation, and combined using Rubin’s rules. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LR), distant metastases (DM), and breast cancer mortality (BCM). Among 5197 patients in the discovery cohort, 639 (12%) were staged with sentinel node biopsy only, 2848 (55%) received PMRT, and 3641 (70%) received adjuvant chemotherapy (CHT). Median 11 lymph nodes (LN) were dissected. Median follow up was 9.8 years. Patients who received PMRT were significantly younger, had larger tumors, more positive LN (LN+), lymphovascular invasion (LVI), extracapsular extension (ECE), HER2+ disease, positive margins, and more frequently received CHT (all p<0.001). Despite more adverse features, the 10-year unadjusted cumulative incidence rates of LR, DM and BCM were 2.8%, 17% and 14% with PMRT and 7%, 17% and 14% without PMRT, respectively. On multivariable competing risks regression, increased LR was associated with younger age (HR 1.04, p<0.001), larger tumor size (HR 1.19, p = 0.006), grade 3 vs. 1 (HR 2.51, p = 0.002), 3 vs. 1 LN+ (HR 1.54, p = 0.02), LVI (HR 1.48, p = 0.005), and inner vs. outer tumor location (HR 1.56, p = 0.02). Decreased LR was associated with receipt of PMRT (HR 0.31, p<0.001) and CHT (HR 0.44, p<0.001). Increased DM was associated with younger age (HR 1.01, p<0.001), larger tumor size (HR 1.32, p<0.001), grade (grade 2 vs. 1 HR 2.01, p<0.001; grade 3 vs. 1 HR 3.07, p<0.001), 3 vs. 1 LN+ (HR 1.40, p<0.001), N1 vs. N1mic (HR 1.40, p = 0.01), LVI (HR 1.31, p<0.001), ER/PR negative (HR 1.28, p = 0.02), and inner vs. outer tumor location (HR 1.49, p<0.001). Decreased DM was associated with receipt of PMRT (HR 0.84, p = 0.04), CHT (HR 0.64, p<0.001), HER2+ with trastuzumab vs. HER2- (HR 0.60, p = 0.001), and later treatment era (HR 0.85, p = 0.04). Increased BCM was associated with younger age (HR 1.01, p = 0.01), larger tumor size (HR 1.33, p<0.001), grade (grade 2 vs. 1 HR 2.61, p<0.001; grade 3 vs. 1 HR 4.06, p<0.001), 3 vs. 1 LN+ (HR 1.39, p = 0.002), N1 vs. N1mic (HR 1.69, p = 0.03), LVI (HR 1.28, p = 0.002), ER/PR negative (HR 1.59, p<0.001), and inner vs. outer tumor location (HR 1.49, p<0.001). Decreased BCM was associated with CHT (HR 0.55, p<0.001) and HER2+ with trastuzumab vs. HER2- (HR 0.56, p = 0.001). Margin status and ECE were not significantly associated with any endpoints. At 10 years median follow up, PMRT for pT1-2N1 breast cancer is associated with decreased LR and DM. Nomograms will be generated and tested in a validation cohort to assist clinicians in individualizing risk estimates in contemporary practice.