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

Abstract Background In clinically node-positive (cN+) patients, radioactive iodine (¹²⁵I) 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 ¹²⁵I seed) and non-MARI nodes and evaluated the association between ¹²⁵I 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 ¹²⁵I 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, ¹²⁵I 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, ¹²⁵I seed absorbed radiation dose had no significant effect on histopathologic features in MARI nodes.