In a Korean phase III trial reported in JAMA Oncology, Kim et al found that the addition of internal mammary node irradiation to adjuvant regional nodal irradiation did not improve 7-year disease-free survival in women with node-positive breast cancer. In an ad hoc analysis, however, benefit was observed in the subgroup of patients with medially or centrally located tumors.
Study Details
In the multicenter trial, 735 women with node-positive disease after breast-conservation surgery or mastectomy with axillary lymph node dissection were randomly assigned to receive regional nodal irradiation along with breast or chest wall irradiation with (n = 362) or without (n = 373) internal mammary node irradiation. Patients with distant metastases and those who had received neoadjuvant treatment were excluded from the trial. Adjuvant taxane-based chemotherapy was received by 98.9% of patients and adjuvant endocrine therapy was received by 67.2%.
The primary endpoint was 7-year disease-free survival in the intent-to-treat population.
Disease-Free Survival
Median follow-up was 100.4 months (interquartile range = 89.7–112.1 months). Disease-free survival at 7 years was 85.3% in the internal mammary node irradiation group vs 81.9% in the no internal mammary node irradiation group (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.57–1.14, P = .22).
Rates at 7 years were 8.4% vs 10.8% (HR = 0.74, 95% CI = 0.47–1.16, P = .19) for breast cancer mortality, 85.8% vs 83.2% (HR = 0.81, 95% CI = 0.56–1.16, P = .25) for distant metastasis–free survival, and 89.4% vs 88.2% (HR = 0.87, 95% CI = 0.57–1.31, P = .50) for overall survival.
An ad hoc subgroup analysis among 306 patients (153 in each group) with medially or centrally located tumors showed significantly improved 7-year disease-free survival (91.8% vs 81.6%, HR = 0.42, 95% CI = 0.22–0.82, P = .008) and breast cancer mortality (4.9% vs 10.2%, HR = 0.41, 95% CI = 0.17–0.99, P = .04) with internal mammary node irradiation vs no internal mammary node irradiation.
Adverse Events
No significant differences in rates of toxic effects were observed between the internal mammary node irradiation vs no internal mammary node irradiation groups, including 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%), or cardiac toxicity (2.2% vs 1.3%). A nonsignificant higher rate of radiation pneumonitis was observed in the internal mammary node irradiation group (6.1% vs 3.2%, P = .06); no grade ≥ 3 radiation pneumonitis was observed in either group.
The investigators concluded, “This randomized clinical trial found that including internal mammary node irradiation in regional nodal irradiation did not significantly improve disease-free survival in patients with node-positive breast cancer. However, patients with medially or centrally located tumors may benefit from the use of internal mammary node irradiation.”
Chang-Ok Suh, MD, PhD, of the Department of Radiation Oncology, Bundang CHA Medical Center, CHA University, Seongnam-si, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the National R&D Program for Cancer Control of the Ministry for Health, Welfare, and Family Affairs of Korea. For full disclosures of the study authors, visit jamanetwork.com.
