Abstract
Published studies on the risk of radiation-induced second primary malignancy (SPM) after radioiodine treatment (RAI) of differentiated thyroid cancer (DTC) refer mainly to patients treated as middle-aged or older adults and are not easily generalizable to those treated at a younger age. Here we review available literature on the risk of breast cancer as an SPM after RAI of DTC with a focus on females undergoing such treatment in childhood, adolescence, or young adulthood. Additionally, we report the results of a preliminary international survey of patient registries from academic tertiary referral centers specializing in pediatric DTC. The survey sought to evaluate the availability of sufficient patient data for a potential international multicenter observational case–control study of females with DTC given RAI at an early age. Our literature review identified a bi-directional association of DTC and breast cancer. The general breast cancer risk in adult DTC survivors is low, ~2%, slightly higher in females than in males, but presumably lower, not higher, in those diagnosed as children or adolescents than in those diagnosed at older ages. RAI presumably does not substantially influence breast cancer risk after DTC. However, data from patients given RAI at young ages are sparse and insufficient to make definitive conclusions regarding age dependence of the risk of breast cancer as a SPM after RAI of DTC. The preliminary analysis of data from 10 thyroid cancer registries worldwide, including altogether 6,449 patients given RAI for DTC and 1,116 controls, i.e., patients not given RAI, did not show a significant increase of breast cancer incidence after RAI. However, the numbers of cases and controls were insufficient to draw statistically reliable conclusions, and the proportion of those receiving RAI at the earliest ages was too low.In conclusion, a potential international multicenter study of female patients undergoing RAI of DTC as children, adolescents, or young adults, with a sufficient sample size, is feasible. However, breast cancer screening of a larger cohort of DTC patients is not unproblematic for ethical reasons, due to the likely, at most slightly, increased risk of breast cancer post-RAI and the expected ~10% false-positivity rate which potentially produced substantial “misdiagnosis.”
Highlights
Treatment of differentiated thyroid cancer (DTC) in childhood, adolescence, or early adulthood with surgery, radioiodine therapy (RAI), and thyroid hormone replacement achieves 10-year survival rates of 95%, with relatively low recurrence rates of 10–30% [1]
In addition to the 64 publications located through the automated search that were deemed to be of potential interest based on their abstracts, a manual search considering the bibliographies of the review articles retrieved 35 citations deemed to be of potential interest based on their abstracts
To summarize today’s state of knowledge, independent of DTC treatment, there appears to be a bi-directional association of DTC itself and breast cancer
Summary
Treatment of differentiated thyroid cancer (DTC) in childhood, adolescence, or early adulthood with surgery, radioiodine (iodine-131, I-131) therapy (RAI), and thyroid hormone replacement achieves 10-year survival rates of 95%, with relatively low recurrence rates of 10–30% [1]. An excellent long-term survival may be partly offset by an increased risk for second primary malignancy (SPM) related to RAI or other causes. According to a systematic review by Clement et al [2], the risk for SPM is increased after RAI of DTC. A recent meta-analysis did not find an increased risk of solid cancers after RAI [5]. Based on the recently introduced radiation risk assessment tool of the United States National Cancer Institute, a dose of 2 Gy to the breast of a 10-year-old girl hypothetically doubles her lifetime risk for breast cancer, whereas in a 50-yearold woman, the risk increases only by 20% [8]
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