Analysis Links Radioactive Iodine Therapy to Breast Cancer Risk

By: Kerry Dooley Young

From: medscape.com

Radioactive iodine (RAI) treatment for hyperthyroidism was associated with an increased incidence of breast cancer but not with an overall increase in cancer incidence or mortality, a new study found.

Researchers analyzed data from the University of Michigan’s de-identified database, examining cancer diagnoses among patients treated for hyperthyroidism between January 1, 2006, and December 30, 2019. They evaluated outcomes among patients treated with RAI, antithyroid medications (propylthiouracil or methimazole), or thyroidectomy.

RAI treatment was significantly associated with an increased risk for breast cancer in both age-adjusted (hazard ratio [HR], 1.70; P = .012) and multivariable models (HR, 2.24; P = .012), reported Alison Mondul, PhD, MSPH, associate professor of epidemiology at the University of Michigan School of Public Health in Ann Arbor, Michigan, and co-authors.

When stratified by menopausal status, RAI treatment was significantly associated with an increased risk for breast cancer among postmenopausal women (aged ≥ 50 years) in both age-adjusted (HR, 1.78; P = .010) and multivariable models (HR, 2.65; P = .011) but not among premenopausal women (aged < 50 years).

“While RAI therapy remains effective for hyperthyroidism management, its observed association with breast cancer highlights the need for long-term safety monitoring and tailored screening protocols to ensure that its benefits outweigh the risks,” the authors wrote.

Confidence in RAI Therapy

In an email exchange with Medscape Medical News, Mondul stressed that the findings should not undermine confidence in RAI treatment.

“It remains an effective and well-established treatment for hyperthyroidism,” she said. “However, the observed association with breast cancer highlights the importance of continued long-term safety monitoring and may support consideration of individualized risk assessment when selecting treatment.”

“For example, clinicians may want to carefully evaluate whether a patient is at high risk for breast cancer when discussing treatment options and deciding between radioactive iodine and other available therapies,” she added.

The study also identified an elevated rate of pancreatic cancer mortality among patients with at least 2 years of follow-up (age-adjusted HR, 4.05; P = .042).

“Limited prior evidence exists linking pancreatic cancer to therapeutic RAI doses, but pancreatic tissue is known to express (sodium-iodine supporters), suggesting a plausible biological mechanism for radiation exposure and cancer,” the authors wrote.

However, they cautioned that the finding requires confirmation.

“Given the rarity of pancreatic cancer and its high mortality rate, future studies with larger sample sizes are essential to validate our findings,” they noted.

Medical News. “We viewed it as a signal that warrants further investigation rather than a conclusive finding.”

Ongoing Debate Around RAI Therapy

The findings add to a substantial body of research examining potential links between RAI therapy and cancer, with mixed conclusions to date.

RAI has been used to treat hyperthyroidism since 1941. Concerns about its long-term safety stem in part from studies of atomic bomb survivors, which showed an increased risk for leukemia after radiation exposure.

A major resource in this research is the Cooperative Thyrotoxicosis Therapy Follow-up Study, which followed people with hyperthyroidism (mainly Graves disease) treated with radiation between 1946 and 1964.

More recently, a 2019 National Cancer Institute analysis reported an association between RAI dose and long-term mortality risk for death from solid cancers, including breast cancer. However, that study has been debated, in part because it relied on external comparison groups.

To address these concerns, Mondul and colleagues designed a cohort study within a single primary care system to ensure more reliable and consistent clinical data. The final cohort included 6435 patients treated for hyperthyroidism, most commonly due to Graves disease.

The authors acknowledged several limitations, including its reliance on patients from a single healthcare system and the potential for detection bias.

“Patients treated with antithyroid medications may require a closer clinical monitoring of thyroid function compared to those treated with RAI, potentially leading to increased cancer detection in this group and thereby underestimating the RAI-cancer association,” they wrote.

Expert Perspective

Kaniksha Desai, MD, endocrinologist and clinical associate professor at Stanford School of Medicine in Stanford, California, who was not involved in the study, said additional details on RAI dose and cumulative radiation exposure would have strengthened the analysis because these factors could influence the risk for cancer.

However, she highlighted the study’s comparison of patients with hyperthyroidism who did and did not receive RAI as a key strength.

“Many prior studies compared RAI-treated patients with the general population, which can introduce bias because hyperthyroidism itself may influence cancer risk or cancer screening, potentially leading to higher numbers of cases being diagnosed,” Desai told Medscape Medical News.

The study supports other evidence suggesting that RAI does not appear to increase the overall risk for cancer in a meaningful way for most patients, she said.