Internal mammary node irradiation in 4541 node-positive breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (DBCG IMN2): a prospective, nationwide, population-based cohort study
Anders W. Mølby Nielsen, Lise Bech Jellesmark Thorsen, Demet Özcan, Louise W. Matthiessen, Else Maae, Marie L.H. Milo, Mette Holck Nielsen, Trine Tramm, Jens Overgaard, Birgitte Vrou Offersen
Abstract
Background: Internal mammary node irradiation (IMNI) improves overall survival (OS) in node-positive breast cancer patients. However, the effect is not documented in breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (RT). Therefore, the Danish Breast Cancer Group (DBCG) IMN2 study aimed to investigate the effect of IMNI in node-positive breast cancer patients treated with newer systemic therapies and 3D-based RT. Methods: DBCG IMN2 was a nationwide population-based cohort study prospectively allocating node-positive breast cancer patients with right-sided tumours to IMNI and patients with left-sided tumours to no IMNI in six RT centres. Exclusion criteria were prior malignancies, bilateral breast cancer, neoadjuvant systemic therapy, recurrence before RT, or non-standard RT. Systemic treatment included taxane-based chemotherapy, aromatase inhibitors, and trastuzumab. The primary end-point was OS. Secondary endpoints were breast cancer mortality and distant metastasis. Cox regression analyses were used for adjusted hazard ratios (HR). Clinicaltrial.gov ID: NCT06549920. Findings: In the period January 2007-May 2014, a total of 4541 patients were included. Patient characteristics were distributed evenly between right- and left-sided patients. Median follow-up was 13.7 years for OS. Survival rates at 15 years were 65.0% in patients with IMNI and 60.8% without leading to an adjusted HR of 0.85 (95% CI, 0.76-0.94; p = 0.0016) for OS. Corresponding HRs were 0.84 (95% CI, 0.74-0.95; p = 0.0077) for breast cancer mortality and HR 0.87 (95% CI, 0.78-0.98; p = 0.026) for distant metastasis. No subgroups were identified for the omission of IMNI. The 15-year cumulative incidence of death from ischemic or valvular heart disease was 0.2% (95% CI, 0.0-0.5) in right-sided and 0.7% (95% CI, 0.4-1.2) in left-sided patients. Interpretation: IMNI reduced distant metastasis and breast cancer mortality and improved OS in node-positive breast cancer patients, despite treatment with newer systemic therapies and 3D-based RT. Funding: This work was supported by the Danish Cancer Society and Department of Clinical Medicine, Aarhus University, Denmark.