Postmastectomy Radiation Therapy Following Pathologic Complete Nodal Response to Neoadjuvant Chemotherapy

PURPOSE/OBJECTIVE(S) Postmastectomy radiation therapy (PMRT) is recommended for patients with breast cancer who have positive nodal disease. Whether there is a benefit to PMRT in patients who have cN+ disease at diagnosis, but a pathologic complete response following neoadjuvant chemotherapy (NAC) in the lymph nodes (pCRn) is unknown. The purpose of the present study is to determine if there is a benefit to PMRT in patients who have a pCRn following neoadjuvant chemotherapy, and which subsets of patients may derive the benefit from PMRT following a pCRn. MATERIALS/METHODS This study was conducted using patients from the National Cancer Data Base (NCDB). Patients included in this study were women diagnosed with breast cancer with cT1-4N1-3 disease who had invasive ductal carcinoma histology and received treatment with NAC and then mastectomy. Overall survival (OS) was compared between all patients using the Kaplan- Meier analysis. To further determine if subsets of patients may derive a greater benefit from PMRT, OS was compared after stratifying patients for clinical T stage, clinical N stage, pathologic T stage, and molecular subtype. Multivariable logistic regression ascertained factors associated with PMRT use. Cox proportional hazards modeling determined variables associated with OS. RESULTS A total of 14,960 patients met the selection criteria, of whom 10,092 (67.5%) received PMRT, and 4598 (30.7%) did not. Amongst all patients, there was no difference in OS with the use of PMRT (10-year OS 76.3% vs 78.6%, P = 0.4147). Improvement with the use of PMRT was observed amongst patients with cN3 (10-year OS 73.1% vs 51.7%, P < 0.001), cT3 (10-year OS 77.0% vs 72.2%, P = 0.0154) or cT4 (10-year OS 69.6% vs 59.1%, P = 0.0001) disease, ypT2 (10-year OS 72.9% vs 65.0%, P = 0.0053) or ypT3 disease (10-year OS 62.3% vs 45.3%, P = 0.0466), as well as patients with ER+HER2+ disease (10-year OS 85.4% vs 56.5%, P = 0.0225). Factors predictive of PMRT use include younger age, Private health insurance, higher socioeconomic status, cT2/3/4 stage, and cN2/3 stage. On multivariate analysis, factors predictive of worse OS include increasing age, Charlson Deyo Comorbidity score ≥ 2, cT3 or cT4 disease, cN2 or cN3 disease, ypT1-4 disease, progression of the primary tumor after neoadjuvant chemotherapy, or ER-HER2- disease. CONCLUSION The extent of nodal disease and primary tumor size both at diagnosis and following NAC may be able to select for patients with pCRn most likely to benefit from PMRT. Further research is required to confirm these findings and to select the patients most likely to benefit from PMRT following NAC and mastectomy.