Feasibility Study Shows Multicenter, Observational Case-Control Study Is Practicable to Determine Risk of Secondary Breast Cancer in Females With Differentiated Thyroid Carcinoma Given Radioiodine Therapy in Their Childhood or Adolescence; Findings Also Suggest Possible Fertility Impairment in Such Patients.

Objective: This single-center, observational case-control feasibility study sought to test key elements of a protocol for an eventual long-term international observational case-control study of a larger patient cohort, to evaluate the risk of breast cancer as a second primary malignancy in females with differentiated thyroid cancer (DTC) given radioiodine therapy (RAI) during childhood or adolescence. Patients: Females developing DTC after the Chernobyl accident in Belarus and ≤19 years old at the time of thyroid surgery were enrolled: patients given RAI (n = 111) and controls of similar age not given RAI (n = 90). Results: One case of breast cancer was newly diagnosed among the RAI patients, but none in controls. Patients given RAI significantly less frequently needed 2nd surgeries than did controls (23%, 26/111 vs. 39%, 35/90, P < 0.05); the main indication for such procedures usually is suspicion of local recurrence. RAI patients appeared to have had more frequent reproductive difficulties than did controls: 78% (87/111) of the former vs. 93% (84/90) of the latter had a history of pregnancy (P < 0.01), and the mean number of pregnancies was 1.5 ± 1.2 in RAI patients vs. 1.9±1.1 in controls (P < 0.05). Most notably, infertility was observed in 23% (26/111) of RAI patients vs. 4% (4/90) of controls (P < 0.01). In conclusion, a international observational case-control study on breast cancer after DTC in patients given RAI vs. not given RAI appears to be feasible. Additional research and everyday clinical attention should be devoted to reproductive function after RAI in young females.

Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey.

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."