Women with hyperthyroidism have an increased risk of developing breast cancer that increases over time, say Danish researchers who also found that hypothyroidism was associated with a reduced breast cancer risk.
In a nationwide population registry study of more than four million women, they found that hyperthyroidism was associated with an 11% increased risk of developing breast cancer, and hypothyroidism was linked to a 6% decreased risk.
Lead author Mette Søgaard, DVM, PhD, of the department of clinical epidemiology, Aarhus University Hospital, Denmark, said in a press release: "Our findings emphasize the importance of raising awareness of breast cancer in women with hyperthyroidism and further our understanding of this potential risk."
High levels of thyroid hormone can have estrogenlike effects, "which may explain why hyperthyroidism is associated with a higher risk of breast cancer," she noted.
However, study coauthor Jens Otto Lunde Jørgensen, MD, clinical professor of endocrinology and internal medicine, also at Aarhus University Hospital, told Medscape Medical News that the findings should not cause undue alarm.
"I don't think that our data justify [the requirement] that all women with excessive thyroid hormone production should...undergo screening with mammography."
The study was published online February 11 in the European Journal of Endocrinology, and follows news that patients with thyroid cancer are at increased risk of breast cancer ― roughly double the risk expected in the general population for a second malignancy ― and vice versa, as previously reported by Medscape Medical News.
An Association, But Is There Cause and Effect?
In the current study, the team examined data from several nationwide databases, including the Danish National Patient Registry, to identify all women in Denmark with a first-time hospital diagnosis of hypo- or hyperthyroidism between 1978 and 2013.
They then linked these women to the Danish Cancer Registry to determine who developed breast cancer. Breast cancer stage at diagnosis and estrogen receptor (ER) status were retrieved. The Charlson Comorbidity Index was also determined.
From a total study population of 4,177,429 women, researchers identified 61,873 diagnosed with hypothyroidism at a median age of 71 years and 80,343 diagnosed with hyperthyroidism at a median age of 70 years. The majority of women in both groups (65.8% and 74.8%, respectively) had no comorbidities, and 8.5% and 3.5%, respectively, were obese.
Median follow-up was 4.9 years and 7.4 years, respectively. Compared with the general population, women with hyperthyroidism had a standardized incidence ratio (SIR) of breast cancer of 1.11, rising to 1.13 after 5 years of follow-up. Women with hypothyroidism had an SIR of breast cancer of 0.94, which did not change over time.
The findings were largely unaffected by stratification by cancer stage at diagnosis, ER status, age, comorbidity, history of alcohol-related disease, and clinical diagnosis of obesity.
Dr Jørgensen said he has not yet calculated the absolute numbers that the increased risk represents.
"What we have shown is that there's an association between a diagnosis of active thyroid disease and an 11% increased risk in subsequently being diagnosed with breast cancer."
But these are registry data and it is only associations that have been studied, both limiting factors, said Dr Jørgensen, stressing he is reluctant to attribute causation.
A potential explanation is that women diagnosed with thyroid disease see their doctor more frequently and are therefore more likely to undergo breast cancer screening.
"We should be a little careful about saying that overactive thyroid disease causes breast cancer because we cannot say that," he emphasized, describing the current findings as "a small piece of a big puzzle."
Hypothyroidism Diagnosis Likely Increased Because of More Testing
Another finding was that the proportion of women diagnosed with hypothyroidism increased during the study period, with 15.0% diagnosed between 1998 and 2002 vs 35.2% between 2008 and 2013.
But the corresponding figures for hyperthyroidism stayed relatively stable, at 20.4% and 20.6%, respectively.
Dr Jørgensen speculated that the increase in hypothyroidism diagnoses may be related to increases in the measurement of thyroid-stimulating hormone in recent years.
"There's little doubt in my mind that it has to do with more intense biochemical screening for thyroid function," he noted. "Whether or not there is also, in addition to this, a true increase in the disease and not only is a diagnostic workup bias a possibility, but I think the main reason is that we test many more patients for it."
The authors report no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. The study was supported by the Program for Clinical Research Infrastructure (PROCRIN), established by the Lundbeck and Novo Nordisk Foundations; the Danish Cancer Society; and the Aarhus University Research Foundation.
Eur J Endocrinol. 2016;174:409-414. Article