IMNI Does Not Significantly Improve DFS in Node+ Breast Cancer But Could Benefit Medically/Centrally Located Tumors


Patients with node-positive breast cancer did not have a significant improvement in disease-free survival with the addition of internal mammary node irradiation to regional nodal irradiation; however, patients with medically or centrally located tumors could benefit.

Disease-free survival (DFS) was not significantly improved with the addition of internal mammary node irradiation (IMNI) to regional nodal irradiation for patients with node-positive breast cancer, although patients with medically or centrally located tumors may still derive benefit according to a study published in JAMA Oncology.

The 7-year DFS rate was 81.9% for those who didn’t undergo IMNI compared with 85.3% for those who received IMNI (HR, 0.80; 95% CI, 0.57-1.14; log-rank P = .22). Findings from an ad-hoc subgroup analysis indicated that the 7-year DFS in those who didn’t receive IMNI was 81.6% compared with 91.8% for those with IMNI (HR, 0.42; 95% CI, 0.22-0.82; log-rank P = .008). Moreover, the 7-year breast cancer mortality rates were 10.2% vs 4.9% in each group, respectively (HR, 0.41; 95% CI, 0.17-0.99; log-rank P = .04). The 7-year distant metastases-free survival (DMFS) rate was 83.2% vs 85.8% (HR, 0.81; 95% CI, 0.56-1.16; log-rank P = .25), and the 7-year overall survival rate was 88.2% vs 89.4% in the IMNI group and non-IMNI group, respectively (HR, 0.87; 95% CI, 0.57-1.31; log-rank P = .50).

A subgroup analysis showed that patients with mediocentrally located tumors had significant DFS improvement with IMNI compared with those with lateral location tumors (HR, 1.05; 95% CI, 0.69-1.62; log-rank P = .81). At 7-years, the breast cancer mortality was not significantly different between the groups in those with laterally located tumors (HR, 0.91; 95% CI, 0.53-1.57; log-rank P = .74). Additionally, the 7-year DMFS rate was 82.3% in the non-IMNI group vs 91.8% in the IMNI group in patients with mediocentrally located tumors (HR, 0.44; 95% CI, 0.23-0.85; log-rank P = .01).

“IMNI has clinical significance for eradicating tumor cells in the IMN area, which can lead to distant and regional disease control. The effectiveness of IMNI is controversial, particularly in patients with medially-located tumors or positive axillary nodes, because the chance of microscopic disease involvement is high,” the study investigators wrote.

A total of 735 patients were enrolled, 373 of whom were included in the non-IMNI group and 362 were in the IMNI group. The median follow-up was 100.4 months. Patients had a median age of 49.0 years. Most patients had T2 tumors (56.1%) and a smaller group had T1 tumors (31.3%). Additionally, most patients had N1 nodal stage (41.4%), while others had N2 (36.6%) and N3 (22.0%) staging. The majority had estrogen receptor–positive (71.3%) and progesterone receptor–positive (62.4%) disease. Approximately half of all patients underwent breast-conserving surgery (49.9%) or modified radical mastectomy (50.1%). The median radiation dose to the treated area was 50.4 Gy with a fractionation of 1.8 Gy.

In the non-IMNI group, 47 patients died compared with 42 in the IMNI group, with the main cause of death being breast cancer. Other causes of death were more frequent in those treated with IMNI than without. Recurrence was reported in 18.5% of patients in the non-IMNI group vs 16.0% of those in the IMNI group. Regional recurrence was also reported in 4.3% of those in the IMNI group and 2.2% in the non-IMNI group.

Adverse effects in the IMNI group and non-IMNI group, respectively, included arm edema (24.0% vs 22.3%), brachial plexopathy (0.8% vs 0.5%), rib fracture (1.1% vs 0.3%), skin reaction (17.7% vs 18.2%), soft tissue fibrosis and necrosis (1.4% vs 1.3%), and cardiac problems (2.2% vs 1.3%). Patients in the IMNI group had higher rates of pneumonitis, but the difference was not significant (6.1% vs 3.2%; P = .06).


Kim YB, Byun HK, Kim DY, et al. Effect of elective internal mammary node irradiation on disease-free survival in women with node-positive breast cancer: a randomized phase 3 clinical trial. JAMA Oncol. 2022;8(1):96-105. doi:10.1001/jamaoncol.2021.6036

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