Histopathological evaluation of local effects of radioactive iodine seeds in axillary lymph nodes in clinically node-positive breast cancer treated with neoadjuvant systemic therapy

Background In clinically node-positive (cN+) patients, radioactive iodine ( 125 I) seeds can be considered to mark metastatic axillary lymph nodes before neoadjuvant therapy (MARI-procedure) but potential therapeutic effects remain unclear. This study compared histopathologic features between MARI (containing 125 I seed) and non-MARI nodes and evaluated the association between 125 I seed absorbed radiation dose and histopathologic features in MARI nodes. Methods This retrospective study included cN+ patients from the Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy (SLNB) (RISAS)-trial (NCT02800317). Non-MARI nodes comprised SLNB or completion axillary lymph node dissection nodes. An expert breast pathologist reviewed MARI and non-MARI nodes with residual disease for the presence of fibrosis, mucin pools, foamy histiocytes, capsular invasion, and residual disease (size). Differences were analysed using multilevel logistic regression. The effect of 125 I seed absorbed radiation dose (Gy) in MARI nodes was evaluated using univariable logistic regression. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results 106 MARI and 326 non-MARI nodes were included from 127 patients. Fibrosis, foamy histiocytes, and macrometastases were significantly more frequent in MARI compared to non-MARI nodes, with ORs of 21.5 (95% CI: 9.51-57.12), 17.1 (95% CI: 3.53-82.44), and 2.3 (95% CI:1.22-4.37). In MARI nodes, 125 I seed absorbed radiation dose had no significant effect on histopathologic features, with ORs between 1.0-1.1. Conclusions Fibrosis, foamy histiocytes, and macrometastases were significantly more present in MARI compared to non-MARI nodes. Moreover, 125 I seed absorbed radiation dose had no significant effect on histopathologic features in MARI nodes.