Impact of Regional Nodal Irradiation on the Outcomes of N1 Breast Cancer Patients Referred for Adjuvant Treatment: A Patient-Level Pooled Analysis of 2 Clinical Trials

Abstract

PurposeTo evaluate the impact of regional nodal irradiation (RNI) among N1 operable breast cancer patients who underwent adequate axillary dissection and received adjuvant chemotherapy. Patients and MethodsThis is a pooled analysis of 812 breast cancer patients referred for adjuvant systemic therapy in 2 prospective randomized studies: NCT00174655 (BIG 02/98) and NCT00312208 (BCIRG005). Overall survival was assessed according to whether patients received supraclavicular and/or internal mammary radiotherapy through Kaplan-Meier estimates. Univariate and multivariate analyses of variables affecting overall and relapse-free survival were performed through Cox regression analysis. Additionally, recurrence rates were analyzed according to regional irradiation patterns. ResultsRegional relapse rates (after a median follow-up of 76 months) were 1.5% in both groups of patients who received or did not receive supraclavicular radiotherapy. The risk of regional recurrence was 0.7% in patients who received internal mammary node radiotherapy versus 1.6% in patients who did not receive internal mammary node radiotherapy. The following factors were associated with worse overall survival in multivariate Cox regression analysis: age < 40 years (P < .0001), > T1 stage (P = .003), and negative hormone receptor status (P = .002). Neither supraclavicular nor internal mammary radiotherapy was associated with improvement in overall or relapse-free survival in Cox regression analysis. ConclusionThe current analysis does not endorse the routine use of supraclavicular or internal mammary radiotherapy among N1 operable breast cancer patients who have undergone adequate dissection of axillary lymph nodes and who have received standard adjuvant systemic therapy. Given the limited power and potential selection bias of the current analysis, further prospective studies are needed to tackle this research question.