Obesity in women increase their risk of developing breast cancer by 20 to 40 percent when compared to women at a healthy weight, reports the National Cancer Institute. There are a number of different studies that have found reasons for the link between obesity and breast cancer development.
Researchers uncovered a basic cause of the disease. After a woman undergoes menopause, fat tissue stimulates estrogen growth. The estrogen then leads to tumor development. Researchers from the University of Colorado Cancer Center were curious why obese women continued to have aggressive tumor growth after anti-estrogen treatment.
The researchers looked at animal models of obesity and breast cancer, specifically rats, and found that these animals have very sensitive androgen receptors, according to a press release from the University of Colorado Anschutz Medical Campus.
The research paper was published in the scientific journal Hormones & Cancer and explains that sensitive androgen receptors amplify the growth signals coming from the hormone testosterone. The androgen receptors in obese rats drove tumor growth and breast cancer development.
“Our original goal was to make a model of obesity and breast cancer that would reflect the condition in women,” said Elizabeth Wellberg, PhD, author of this research paper. “At first, we were disappointed to discover that rats don’t make much estrogen in fat tissue like humans do.”
“But we then realized that this aspect of the model gave us an excellent opportunity to study cancer progression after anti-estrogen treatment,” Wellberg continued. “Because fat cells in these rats don’t make estrogen, they are like human breast cancer patients treated to remove estrogen. This allowed us to ask what is responsible for obesity-associated tumor progression in conditions of low estrogen availability.”
In the United States, nearly two out of five women are defined as obese and three out of four breast cancers are estrogen-receptor positive. The majority of estrogen-receptor positive breast cancers receive anti-estrogen therapies.
Androgen receptors and testosterone have been known to drive the growth of prostate cancer. This research points at the idea that androgen receptors may also be part of breast cancer growth.
The researchers then treated the animal models with the anti-androgen medicine enzalutamide and found that the existing tumors actually decreased in size. Other new tumors did not form either.
However, the researchers continued to question the process of breast cancer development in terms of androgen receptors. What was causing the overactive androgen receptors and why were these receptors more sensitive to testosterone?
The researchers noticed that the interleukin 6 (IL-6) cytokine was found in higher levels among obese rats and associated with inflammation. Essentially, obesity leads to inflammation and higher rates of IL-6. The study shows that IL-6 led to more sensitized androgen receptors. Sensitive androgen receptors then lead to breast cancer development by magnifying the growth signals of testosterone.
“Down the line, we can imagine a day in which the BMI or metabolic state of breast cancer patients would be considered when choosing a treatment. These patients may benefit significantly from a more personalized therapeutic strategy, based on what obesity is doing to the tumor environment,” Wellberg concluded.