Excluding Axillary Level I from the Regional Nodal Irradiation Field is not Associated with an Increased Axillary Recurrence in Patients with Breast Cancer

Abstract

<h3>Purpose/Objective(s)</h3> The efficacy of regional nodal irradiation (RNI) in patients with breast cancer has been established in several phase 3 clinical trials. However, the optimal RNI field design has not been elucidated in detail. Irradiation of upper axillary level I is controversial and tends to be done at physicians' discretion as surgical exploration is usually performed in this area. We aimed to investigate whether the exclusion of axillary level I from RNI field affects axillary recurrence. <h3>Materials/Methods</h3> We retrospectively identified women with non-metastatic and unilateral breast cancer receiving RNI after breast cancer surgery from 2007 to 2018. Patients were classified into extensive and limited RNI groups according to the inclusion of axillary level I in the nodal field. Extensive RNI and limited RNI were defined by the lateral border of the nodal field encompassing and not encompassing the humeral head, respectively. To adjust baseline characteristics between the groups, propensity score matching was performed. Additionally, non-inferiority of limited RNI was defined as ≤2% excess of the 5-year axillary recurrence rate. <h3>Results</h3> Among 1780 patients, 1020 patients were matched (510 patients in each group). The median number of positive and removed lymph nodes were 1 and 10, respectively. Initial clinical N stage was N0 in 24.1%, N1 in 51.0%, N2 in 14.0%, and N3 in 10.9%. The median follow-up of 67.9 months (interquartile range, 43.1–96.4 months). The 5-year axillary recurrence rate was 1.2% (95% CI, 0.2%–2.1%) in extensive RNI group and 1.6% (95% CI, 0.4%–2.8%) in limited RNI group (P_log-rank=0.790). Non-inferiority of limited RNI was established with a difference between groups of 0.4% (95% CI, -1.1%–1.9%, P_{non-inferiority}=0.018). Subgroup analyses were performed according to the tumor location, the number of removed nodes, the lymph node ratio (ratio of positive over removed nodes), Ki-67, cN stage, pN stage, hormone receptor, lymphovascular invasion, and perinodal extension, but axillary level I irradiation did not significantly reduce axillary recurrence rate in none of the subgroups. Multivariable analysis showed younger age (HR, 1.07, per age; P=0.034), less than 10 removed nodes (HR, 4.50; P=0.029), and the presence of lymphovascular invasion (HR, 8.13; P=0.006) were associated with the higher risk of axillary recurrence, but limited RNI was not (P=0.355). <h3>Conclusion</h3> Excluding axillary level I from the RNI field did not increase axillary recurrence in women with breast cancer. When RNI is performed, upper axillary level I area can be saved from irradiation.