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

**Authors:** Florien J.G. van Amstel, Janine M. Simons, Loes Kooreman, Melissa Lenaerts, Sander M.J. van Kuijk, Lars H.P. Murrer, Cornelis M. de Mooij, Ernest J.T. Luiten, Carmen C. van der Pol, Linetta B. Koppert, Marjolein L. Smidt, Paul J. van Diest, Thiemo J.A. van Nijnatten

PMC · DOI: 10.1016/j.breast.2026.104746 · The Breast : Official Journal of the European Society of Mastology · 2026-03-04

## TL;DR

This study found that radioactive iodine seeds in lymph nodes of breast cancer patients caused more fibrosis and other changes, but the radiation dose had no significant effect.

## Contribution

The study provides new insights into the local histopathological effects of radioactive iodine seeds in axillary lymph nodes.

## Key findings

- MARI nodes showed significantly more fibrosis, foamy histiocytes, and macrometastases compared to non-MARI nodes.
- The absorbed radiation dose from 125I seeds had no significant effect on histopathologic features in MARI nodes.

## Abstract

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.

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).

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 and 1.1.

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.

•Analysis of local effects of 125I seed-marked nodes in node-positive breast cancer.•Nodes with and without 125I seed with residual disease were compared.•125I seed-marked nodes showed more fibrosis, foamy histiocytes, and macrometastases.•125I seed absorbed radiation had no significant effect on histopathologic features.

Analysis of local effects of 125I seed-marked nodes in node-positive breast cancer.

Nodes with and without 125I seed with residual disease were compared.

125I seed-marked nodes showed more fibrosis, foamy histiocytes, and macrometastases.

125I seed absorbed radiation had no significant effect on histopathologic features.

## Linked entities

- **Chemicals:** 125I (PubChem CID 131873571)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, Mucin [NCBI Gene 100508689], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}
- **Diseases:** hemorrhage (MESH:D006470), prostate cancer (MESH:D011471), cytotoxic (MESH:D064420), fibroelastosis (MESH:D004695), NST (MESH:D016609), residual disease (MESH:D018365), node (MESH:D012804), Fibrosis (MESH:D005355), tumour (MESH:D009369), breast cancer (MESH:D001943), granuloma (MESH:D006099), inflammation (MESH:D007249)
- **Chemicals:** anthracyclines (MESH:D018943), Iodine (MESH:D007455), MARI (-), 125I (MESH:C000614960), trastuzumab (MESH:D000068878), eosin (MESH:D004801), pertuzumab (MESH:C485206), 99mTc (MESH:D013667), haematoxylin (MESH:D006416), taxanes (MESH:D043823)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC13000488/full.md

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Source: https://tomesphere.com/paper/PMC13000488