Breast Cancer More Aggressive in Obese Women

Obese women have a higher risk of breast cancer than their slimmer counterparts. Numerous studies have provided explanations for the discrepancy which include that after menopause fat tissue manufactures estrogen and the estrogen stimulates tumor growth. But obese women continue to have more aggressive tumors than thinner women, even after anti-estrogen treatment.

Why does this happen, experts ask, when estrogen has been removed?

Researchers at the University of Colorado Cancer Center have discovered a possible explanation: In an animal model of obesity and breast cancer (affectionately referred to as the “fat rat”), tumor cells in obese animals, but not lean animals, had especially sensitive androgen receptors.

Androgen is a hormone mainly associated with males, and androgen receptors, along with their hormone partner, testosterone, have long been known as drivers of prostate cancer. But the researchers found that the androgen receptor cells magnified growth signals from the hormone testosterone in obese female rats with breast cancer as well.

Similar to the way in which many breast cancers drive their growth with estrogen receptors, these tumors in obese rats drove their growth with androgen receptors.

“Because fat cells in these rats don’t make estrogen, they are like human breast cancer patients treated to remove estrogen,” said Elizabeth Wellberg, Ph.D.  “This allowed us to ask what is responsible for obesity-associated tumor progression in conditions of low estrogen availability,” she said.

Previously, the Colorado researchers had shown that levels of a component of inflammation known as interleukin 6 (IL-6), were higher in obese rats compared to lean rats. In the current paper, the group shows that administering IL-6 to breast cancer cells amplifies the activity of androgen receptors and drives breast cancer even when estrogen levels are low. When researchers treated their obese rats with the anti-androgen drug enzalutamide, existing tumors shrank and new tumors failed to form.

The study was published in the journal Hormones Cancer.

According to the Susan G. Komen foundation, women who are obese have up to an overall 60 percent higher risk of breast cancer than women who are slim. Postmenopausal women who are obese increase their risk of estrogen receptor-positive breast cancer by 70 percent.

About 12 percent of American women will develop breast cancer during their lifetime. In 2016, 246,660 new cases of invasive cancer are projected to be diagnosed, along with 61,000 new cases of non-invasive (in situ) breast cancer. Over 40,000 American women die from the disease each year.