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 primary systemic treatment remains uncertain.

The aim of the study was 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 primary systemic treatment.

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 in the interval 2014-2021. Patients with intramammary or periclavicular lymph node involvement were excluded. Median (IQR) follow-up was 49 (32-70) months. Data were analyzed during 2025.

After primary systemic treatment, 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.

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

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 radiotherapy. 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 overall survival was 98% (95% CI, 95%-100%); in patients with ypN+, iDFS was 87% (95% CI, 82%-93%) and OS, 93% (95% CI, 89%-97%).

In conclusion, this cohort study found that response-guided axillary treatment, using the MARI protocol, in patients with limited nodal disease who received primary systemic treatment was associated with a very low risk of axillary recurrence and should be considered to protect patients from axillary overtreatment. ( Xagena )

van Hemert AKE et al, JAMA Oncol 2025;11(10):1204-1211

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