Isolated Tumor Cells and Micrometastatic Nodal Disease in Breast Cancer Patients After Neoadjuvant Chemotherapy: Is Post Mastectomy Radiation Therapy Indicated?

Purpose/Objective(s) The prognostic and treatment implications of isolated tumor cells (ypN0i+) and micrometastatic (ypN1mi) nodal disease after neoadjuvant chemotherapy (NACT) is not well-studied. These patients are excluded from the ongoing NSABP B-51 trial which only includes patients with macroscopic nodal disease after NACT. We evaluate the long-term outcomes and the role of post-mastectomy radiation therapy (PMRT) in breast cancer patients with ypN0i+ and ypN1mi disease after NACT and mastectomy (MX). Materials/Methods Using the National Cancer Database (NCDB), we identified patients (≥ 18 year old) with breast cancer who were treated with NACT and MX diagnosed between 2004 and 2016. Patients with cT4 or metastatic disease were excluded. Chi-square testing was used to evaluate clinicopathological parameters of those treated with and without PMRT. Kaplan-Meier analysis was used to evaluate the effect of PMRT on overall survival (OS). Univariate and multivariate Cox proportional hazard models with and without inverse probability treatment weighting (IPTW) were used to identify prognostic factors associated with OS. Results Our final cohort consisted of 3,253 patients (34.0% ypN0i+, 66.0% ypN1mi) with a median age at diagnosis of 49 years (29 – 74 years). PMRT was utilized in 60.4% of the entire cohort, 51.8% of ypN0i+ patients and in 64.9% of ypN1mi patients. There was an increase in use of PMRT throughout the study period (56.2% in 2004-2011 vs. 61.9% in 2012-2016). With a median follow up of 36.8 months, the 5-year OS was 84.3% and 79.9% for ypN0i+ and ypN1mi patients, respectively (HR 1.23 [0.97-1.55], P = 0.092). Without accounting for covariates, there was no significant effect of PMRT on OS in ypN0i+ patients, ypN1mi patients, or in the entire cohort. In IPTW-MVA, PMRT had no significant effect on OS (HR 0.93 [0.74-1.18], P = 0.565]. Factors that were significant for worse OS on IPTW-MVA were higher comorbidity score, higher grade, hormone-receptor negative subtype, higher ypT stage, presence of lymphovascular invasion, Asian/Pacific Islander race, and more recent year of diagnosis. HER-2 positive subtype, receipt of hormone therapy, and private insurance were associated with improved OS. Conclusion Patients with ypN1mi disease had a trend towards worse OS in comparison to patients with ypN0i+ disease. The majority of patients with ypN0i+ and ypN1mi are receiving PMRT with higher rates of PMRT in ypN1mi vs. ypN0i+. PMRT rates are increasing with time. There is no association of PMRT with improved OS. Prospective randomized controlled data is needed to further evaluate the role of PMRT in these patients who were excluded from the ongoing NSABP B-51.