Hypothyroidism associated with reduced breast cancer risk

Discovery could lead to new direction for prevention, treatment research

Researchers at The University of Texas M. D. Anderson Cancer Center have found that women with a common thyroid gland disorder appear to have a reduced chance of developing invasive breast cancer, according to a study published in the March 15 issue of Cancer, out online Feb. 14.

In a retrospective case-control study of 2,226 females, researchers found that women with primary hypothyroidism (under-active thyroid) had a 61 percent lower risk of developing invasive breast cancer. Additionally, women newly diagnosed with breast cancer were 57 percent less likely to have the under-active thyroid gland condition compared to a control group of healthy women.

Even more, the breast cancer patients on the study who also had a history of hypothyroidism tended to be older when diagnosed and have a less aggressive, indolent variety of the disease that was sensitive to estrogen treatment.

“These intriguing and very exciting findings suggest a biological role of thyroid hormone in women with breast cancer that could offer some prognostic or therapeutic value, perhaps suggesting novel preventive strategies,” says Massimo Cristofanilli, M.D., associate professor in M. D. Anderson’s Department of Breast Medical Oncology and the study’s lead author. “The study also draws attention to the role of thyroid hormone and its potential interaction with estrogen to promote the onset of breast cancer. We need to consider that while in the past we’ve looked only at the role of estrogen on breast tissue to promote the onset of cancer – thereby promoting research that brought therapeutic and preventive hormonal approaches to the patient – many more studies need to be done to explore the role of other hormones.

The influence of thyroid gland disease on breast cancer has been debated for some time. Other smaller studies have focused on a population of women with several thyroid conditions, such as hypothyroidism, hyperthyroidism (over-active thyroid), thyroid cancer and others, and reported conflicting results on the incidence of breast cancer. Consequentially, researchers were not sure what to make of the different findings, Cristofanilli says.

M. D. Anderson’s study is the first clinical investigation to examine the characteristics of invasive breast cancer in patients with hypothyroidism and compare the incidence of this common condition with a carefullyselected matched control group. The study compared the medical records of 1,136 women treated at M. D. Anderson for breast cancer to those of 1,088 healthy women who came to the institution for breast cancer screening.

“Thyroid hormone and estrogen both share similar pathways in regulating proliferation and growth in the target cells, including cancer cells. This well known phenomenon of cross-talk between the receptor of these hormones may promote or inhibit thereby determining the “fate” of a cell towards either a regulated growth or a cancer,” he says. “If results of a planned M. D. Anderson prospective study bear out this conclusion, then it may be possible to design a treatment that specifically and narrowly targets thyroid hormone receptors, which might provide enough influence on the target cells to help prevent breast cancer – perhaps even serving as a complement to tamoxifen,” Cristofanilli says.

Even before this research is concluded, Cristofanilli believes that, as a first step, all women diagnosed with breast cancer should have their thyroid function tested to detect common disorders – namely hyper- or hypothyroidism – so that women with both conditions can be closely monitored.

Nuclear receptors for thyroid hormone and estrogen are part of the “superfamily” of receptors that contribute to control cell growth and differentiation. Hormones must bind to this family of important proteins to exert their functions, and depending on the hormone to which they bind, can either stimulate or inhibit the growth of cells, Cristofanilli says.

Estrogen controls growth of female reproductive tissues, such as is found in the breasts, and thyroid hormones control energy metabolism in tissue.

Hypothyroidism – a condition estimated to affect approximately 20 percent of older women – is produced when the thyroid gland, located in the front of the neck, fails to produce enough thyroid hormone. Insufficient levels of specific types of thyroid hormone may affect all body functions, and can slow patient functioning, causing mental and physical sluggishness.

Other researchers contributing to the M. D. Anderson study include: Gabriel Hortobagyi, M.D., chairman of the Department of Breast Medical Oncology; Richard Theriault, D.O.; Therese Bevers, M.D.; Sara Strom, Ph.D.; Savitri Krishnamurthy, M.D.; Yuko Yamamura; Shu-Wan Kau; Modesto Patangan; and Limin Hsu.