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

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

doi:10.1016/j.breast.2026.104746

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

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
,

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 and 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.

Original language	English
Article number	104746
Number of pages	6
Journal	The Breast
Volume	87
Early online date	4 Mar 2026
DOIs	https://doi.org/10.1016/j.breast.2026.104746
Publication status	E-pub ahead of print - 4 Mar 2026

Access to Document

10.1016/j.breast.2026.104746Licence: CC BY

Histopathological evaluation of local effects of radioactive iodine seeds in axillary lymph nodes in clinically node-positive breast cancer treated with neoadjuvant systemic therapyFinal published version, 1.95 MBLicence: CC BY

Cite this

van Amstel, F. J. G., Simons, J. M., Kooreman, L., Lenaerts, M., van Kuijk, S. M. J., Murrer, L. H. P., de Mooij, C. M., Luiten, E. J. T., van der Pol, C. C., Koppert, L. B., Smidt, M. L., van Diest, P. J., van Nijnatten, T. J. A. (2026). Histopathological evaluation of local effects of radioactive iodine seeds in axillary lymph nodes in clinically node-positive breast cancer treated with neoadjuvant systemic therapy. The Breast, 87, Article 104746. Advance online publication. https://doi.org/10.1016/j.breast.2026.104746

@article{12c834977e7e49c09d66bb10bc1096c5,

title = "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 and 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.",

author = "\{van Amstel\}, \{Florien J G\} and Simons, \{Janine M\} and Loes Kooreman and Melissa Lenaerts and \{van Kuijk\}, \{Sander M J\} and Murrer, \{Lars H P\} and \{de Mooij\}, \{Cornelis M\} and Luiten, \{Ernest J T\} and \{van der Pol\}, \{Carmen C\} and Koppert, \{Linetta B\} and Smidt, \{Marjolein L\} and \{van Diest\}, \{Paul J\} and \{van Nijnatten\}, \{Thiemo J A\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors",

year = "2026",

month = mar,

day = "4",

doi = "10.1016/j.breast.2026.104746",

language = "English",

volume = "87",

journal = "The Breast",

issn = "0960-9776",

publisher = "Churchill Livingstone",

}

van Amstel, FJG, Simons, JM, Kooreman, L, Lenaerts, M, van Kuijk, SMJ, Murrer, LHP, de Mooij, CM, Luiten, EJT, van der Pol, CC, Koppert, LB, Smidt, ML, van Diest, PJ, van Nijnatten, TJA 2026, 'Histopathological evaluation of local effects of radioactive iodine seeds in axillary lymph nodes in clinically node-positive breast cancer treated with neoadjuvant systemic therapy', The Breast, vol. 87, 104746. https://doi.org/10.1016/j.breast.2026.104746

Histopathological evaluation of local effects of radioactive iodine seeds in axillary lymph nodes in clinically node-positive breast cancer treated with neoadjuvant systemic therapy. / van Amstel, Florien J G; Simons, Janine M; Kooreman, Loes et al.
In: The Breast, Vol. 87, 104746, 06.2026.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Histopathological evaluation of local effects of radioactive iodine seeds in axillary lymph nodes in clinically node-positive breast cancer treated with neoadjuvant systemic therapy

AU - van Amstel, Florien J G

AU - Simons, Janine M

AU - Kooreman, Loes

AU - Lenaerts, Melissa

AU - van Kuijk, Sander M J

AU - Murrer, Lars H P

AU - de Mooij, Cornelis M

AU - Luiten, Ernest J T

AU - van der Pol, Carmen C

AU - Koppert, Linetta B

AU - Smidt, Marjolein L

AU - van Diest, Paul J

AU - van Nijnatten, Thiemo J A

PY - 2026/3/4

Y1 - 2026/3/4

N2 - 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 and 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.

AB - 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 and 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.

U2 - 10.1016/j.breast.2026.104746

DO - 10.1016/j.breast.2026.104746

M3 - Article

C2 - 41831424

SN - 0960-9776

VL - 87

JO - The Breast

JF - The Breast

M1 - 104746

ER -

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

Access to Document

Fingerprint

Cite this