JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Marie Overgaard, and Jens Overgaard, Aarhus University Hospital, Aarhus; Hella Danø, Herlev Hospital, Herlev; Martin Berg, Vejle Hospital, Vejle; Ingelise Jensen, Aalborg University Hospital, Aalborg; Anders Navrsted Pedersen, Rigshospitalet, Copenhagen; Sune J ¨ urg Zimmermann, Odense University Hospital, Odense, Denmark; and Hans-J ¨ urgen Brodersen, St Franziskus-Hospital, Flensburg, Germany. Published online ahead of print at www.jco.org on November 23, 2015. Written on behalf of the Danish Breast Cancer Cooperative Group Radiotherapy Committee. Supported by the Danish Cancer Society; the Breast Friends breast cancer campaign; and the Lundbeck Foundation Center for Interventional Research in Radiation Oncology, Max and Inger Wørzners Memorial Foundation. Presented in part at the 33rd conference of the European Society for Radiotherapy and Oncology, Vienna, Austria, April 4-8, 2014. Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article. Corresponding author: Lise Bech Jellesmark Thorsen, MD, PhD, Department of Experimental Clinical Oncology, Aarhus University Hospital, Nørrebrogade 44, Bldg 5, DK-8000, Aarhus C, Denmark; e-mail: liseb@oncology.au.dk. © 2015 by American Society of Clinical Oncology 0732-183X/16/3404w-314w/$20.00 DOI: 10.1200/JCO.2015.63.6456 DBCG-IMN: A Population-Based Cohort Study on the Effect of Internal Mammary Node Irradiation in Early Node-Positive Breast Cancer Lise Bech Jellesmark Thorsen, Birgitte Vrou Offersen, Hella Danø, Martin Berg, Ingelise Jensen, Anders Navrsted Pedersen, Sune J¨ urg Zimmermann, Hans-J¨ urgen Brodersen, Marie Overgaard, and Jens Overgaard See accompanying editorial on page 297 A B S T R A C T Purpose It is unknown whether irradiation of the internal mammary lymph nodes improves survival in patients with early-stage breast cancer. A possible survival benefit might be offset by radiation-induced heart disease. We assessed the effect of internal mammary node irradiation (IMNI) in patients with early- stage node-positive breast cancer. Patients and Methods In this nationwide, prospective population-based cohort study, we included patients who underwent operation for unilateral early-stage node-positive breast cancer. Patients with right-sided disease were allocated to IMNI, whereas patients with left-sided disease were allocated to no IMNI because of the risk of radiation-induced heart disease. The primary end point was overall survival. Secondary end points were breast cancer mortality and distant recurrence. Analyses were by intention to treat. Results A total of 3,089 patients were included. Of these, 1,492 patients were allocated to IMNI, whereas 1,597 patients were allocated to no IMNI. With a median of 8.9 years of follow-up time, the 8-year overall survival rates were 75.9% with IMNI versus 72.2% without IMNI. The adjusted hazard ratio (HR) for death was 0.82 (95% CI, 0.72 to 0.94; P = .005). Breast cancer mortality was 20.9% with IMNI versus 23.4% without IMNI (adjusted HR, 0.85; 95% CI, 0.73 to 0.98; P = .03). The risk of distant recurrence at 8 years was 27.4% with IMNI versus 29.7% without IMNI (adjusted HR, 0.89; 95% CI, 0.78 to 1.01; P = .07). The effect of IMNI was more pronounced in patients at high risk of internal mammary node metastasis. Equal numbers in each group died of ischemic heart disease. Conclusion In this naturally allocated, population-based cohort study, IMNI increased overall survival in patients with early-stage node-positive breast cancer. J Clin Oncol 34:314-320. © 2015 by American Society of Clinical Oncology INTRODUCTION Irradiation of the internal mammary lymph nodes (IMNI) has been a subject of controversy since radiotherapy to the chest wall/breast and regional lymph nodes was shown to improve survival in patients with early-stage breast cancer. 1-5 These nodes may harbor metastatic disease, especially in patients with a medially placed tumor or positive axillary nodes. 6 However, neither internal mam- mary node dissection nor radiotherapy has been proven beneficial. 7,8 Depending on treatment technique, IMNI increases the radiation dose to the heart, particularly on the left side. 9 A recent Early Breast Cancer Trialists’ Col- laborative Group (EBCTCG) meta-analysis dem- onstrated the long-term effect of regional radiotherapy after mastectomy in patients with node-positive breast cancer. The absolute reduc- tion in breast cancer mortality at 20 years was 7.9% in patients with one to three positive nodes, and the relative risk of dying from breast cancer was 0.80 (95% CI, 0.67 to 0.95; P = .01). Results were similar for patients with four or more nodes involved. 5 Two concurrent randomized trials on regional radiotherapy in early-stage breast cancer have shown results in favor of more regional radiotherapy. 10,11 In the European Organization for the Research and Treatment of Cancer (EORTC) 314 © 2015 by American Society of Clinical Oncology VOLUME 34 • NUMBER 4 • FEBRUARY 1, 2016 Downloaded from ascopubs.org by 52.73.204.196 on May 17, 2022 from 052.073.204.196 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.