Breast cancer risk after radioiodine therapy of thyroid carcinoma - Project 3615S4242. Final report

The main objective of the feasibility study was to investigate the basic conditions of a long-term international subsequent study of a larger patient cohort, in order to evaluate the risk of breast cancer as a secondary malignancy in female thyroid cancer patients after radioiodine therapy (RIT) during childhood and adolescence. To review the practical workflow, female thyroid cancer patients from Belarus were studied who had been treated either with RIT (patient group) or no RIT (control group) before the age of 19-years. The project consisted of four work packages (WP): In WP1, the current relevant state of the scientific and technical knowledge was presented in a literature review and statements of national and international committees were summarized. These results concerning the risk of breast cancer after RIT were not distinct. In WP2, national and international patient- and control-cohorts eligible for the subsequent study were identified; their characteristics were described. Increasing the age limit from 18 to 40 years, results currently in a total of 3.300 cases and 500 controls in the respective registers. The number of female patients with RIT and controls that could be included as well as currently detectable effects were estimated in a case number calculation and statistical analysis, respectively; thus for the subsequent study, at least 4.340 cases and 660 controls should be included. If an additional three to five international thyroid centers were to be recruited into the subsequent study, this number could be reached. The performance of the feasibility study was planned, the survey instruments were updated, and study methods (mandatory: radiological anamnesis, clinical investigation and ultrasound of breast; concomitantly: follow-up of thyroid cancer and general gynecological anamnesis and investigation) and quality control programs were defined. In WP3, 111 cases after RIT and 90 controls were investigated in Belarus according to the protocols. In WP4, the database was updated; data compiled were analyzed. In the patient group, one case of breast cancer and three cases of cervical cancer were newly diagnosed; in the control group no cancer cases were detected. Due to the small sample size these differences are not significant. Besides some secondary side findings concerning the follow-up of thyroid cancer, the highly significant increased infertility rate in the patients group (23%) compared to the control group (4%) was noticeable. In conclusion, the feasibility study results in following recommendation: Basically, a subsequent study with a sufficiently high number of female patients is feasible; the required program for this purpose including the necessary quality control was successfully tested in the feasibility study. Concerning the conceptual design of the subsequent study, a case-control study in patients <40 years of age with thyroid cancer diagnosed 20-30 years earlier should be preferred over a longitudinal study of several decades for reasons of compliance and practicability. However, breast cancer screening of a larger cohort of thyroid cancer patients is not unproblematic for ethical reasons due to the at best slightly increased risk for breast cancer after RIT and an expected high rate of false positive findings in the range of 10% and an uncertain number of "overdiagnoses". These concerns apply at an even more pronounced way for the control cohort not affected by radiation exposure as a risk-increasing factor. This is why patients and controls have to be actively involved in the decision about breast cancer screening in the sense of a complex "shared decision making". Research needs result from the question of an increased infertility rate after RIT for thyroid cancer. A subsequent study addressing this issue should be feasible with substantially smaller case numbers compared to the topic of breast cancer.