Iodine Seed-Marking Protocol for Response-Guided Axillary Treatment After Systemic Therapy for Node-Positive Breast Cancer.

Importance: Most patients with clinically node-positive (cN+) breast cancer receive primary systemic treatment (PST) followed by axillary lymph node dissection (ALND) and/or locoregional radiation (RT). The necessity of axillary treatment in patients achieving nodal pathologic complete response (pCR) after PST remains uncertain.

Objective: To assess oncologic outcomes of response-guided axillary treatment determined by marking the axillary lymph node with a radioactive iodine seed (MARI) in patients with cN+ breast cancer who experience pCR after PST.

Design, Setting, And Participants: This cohort study was conducted at a single center including patients with breast cancer with 3 or fewer axillary lymph nodes on fluorodeoxyglucose positron emission tomography-computed tomography who were treated according to the MARI protocol from July 2014 to December 2021. Patients with intramammary or periclavicular lymph node involvement were excluded. Median (IQR) follow-up was 49 (32-70) months. Data were analyzed from March to June 2025.

Exposure: After PST, the MARI-marked lymph node was excised. Patients with pCR of the MARI node (ypN0) received no further axillary treatment, whereas patients with residual disease (ypN+) received locoregional radiation therapy.

Main Outcomes And Measures: The primary outcome measure was axillary recurrence rate. The secondary outcome measures were 5-year invasive disease-free survival (iDFS) and overall survival (OS).

Results: In total, 350 patients (median [IQR] age, 49 [41-56] years) were included and analyzed; of these, 135 (39%) had ypN0 and received no further axillary treatment. The remaining 215 patients with ypN+ (61%) received RT. After a median (IQR) follow-up of 49 (32-70) months, axillary recurrence rate was 0.7% (n = 1; 95% CI, 0.04%-4.1%) in patients with ypN0 and 2.3% (n = 7; 95% CI, 1.0%-5.3%) in patients with ypN+. In patients with ypN0, the 5-year iDFS was 93% (95% CI, 88%-98%) and the OS was 98% (95% CI, 95%-100%); in patients with ypN+, iDFS was 87% (95% CI, 82%-93%) and OS, 93% (95% CI, 89%-97%).

Conclusions And Relevance: This cohort study found that response-guided axillary treatment, using the MARI protocol, in patients with limited nodal disease who received PST was associated with a very low risk of axillary recurrence and should be considered to protect patients from axillary overtreatment.