Simple SummaryThe results of this multidisciplinary study can function as a clinician’s guide for determining the preferred surgical localization technique for breast-conserving surgery in pregnant women with breast cancer and its timing, without avoiding the use of a125I-seed. The maximum exposure to the fetus remains well below 100 millisieverts (mSv), the threshold value for tissue damage caused by radiation. If the exposure should remain below 1 mSv, the implantation and surgical removal of the125I-seed should occur within two weeks after a GA of 26 weeks, and within one week after a GA of 32 weeks. The contribution of an axillary seed is negligible (at maximum, 2.3% of the seed implanted in the breast).AbstractIntroduction: Some aspects of the treatment protocol for breast cancer during pregnancy (PrBC) have not been thoroughly studied. This study provides clarity regarding the safety of the use of125I-seeds as a localization technique for breast-conserving surgery in patients with PrBC. Methods: To calculate the exposure to the fetus of one125I-seed implanted in a breast tumor, we developed a model accounting for the decaying125I-source, time to surgery, and the declining distance between the125I-seed and the fetus. The primary outcome was the maximum cumulative fetal dose of radiation at consecutive gestational ages (GA). Results: The cumulative fetal dose remains below 1 mSv if a single125I-seed is implanted at a GA of 26 weeks. After a GA of 26 weeks, the fetal dose can be at a maximum of 11.6 mSv. If surgery takes place within two weeks of implantation from a GA of 26 weeks, and one week above a GA of 32 weeks, the dose remains below 1 mSv. Conclusion: The use of125I-seeds is safe in PrBC. The maximum fetal exposure remains well below the threshold of 100 mSv, and therefore, does not lead to an increased risk of fetal tissue damage. Still, we propose keeping the fetal dose as low as possible, preferably below 1 mSv.