Women with obesity are more likely to get breast cancer, and a number of studies have provided a reasonable explanation why: after menopause, fat tissue manufactures estrogen, and the estrogen then promotes tumor growth. But why, then, do women with obesity continue to have more aggressive tumors even after anti-estrogen treatment ? Once the tumor’s source of estrogen is removed, obesity should have no effect on prognosis, but it does.

A University of Colorado Cancer Center study published in the journal Hormones & Cancer offers a possible explanation: in an animal model of obesity and breast cancer, tumor cells in obese animals, but not lean animals, had especially sensitive androgen receptors, allowing these cells to magnify growth signals from the hormone testosterone.
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.

About 40% of American women have obesity; about 75% of breast cancers are estrogen-receptor positive, most of which will go on to be treated with anti-estrogen therapies.
This combination means that thousands of women every year could benefit from treatments aimed at the aspects of obesity that promote breast cancer in low- or non-estrogen environments.

Androgen receptors and their hormone partner, testosterone, have long been known as drivers of prostate cancer, but androgen is also a driver in many breast cancers.

Researchers at Colorado University treated obese rats with the anti-androgen drug Enzalutamide ( Xtandi ), existing tumors shrank and new tumors failed to form.
But this brought up another question: if overactive androgen receptors create poor prognosis in obese breast cancer patients, what is creating these overactive androgen receptors ? It wasn’t that they were simply responding to more testosterone – it was that these receptors had been somehow tuned to be more sensitive to existing levels of testosterone.

Lean and obese individuals differ in many things: resistance to insulin, high blood glucose level, and an elevated inflammatory response ( chronic low-grade inflammation ).

The researchers had previously shown that a component of inflammation, namely levels of a cytokine known as interleukin 6 ( IL-6 ), is higher in the circulation of obese compared to lean rats.

In the current paper, the researchers have shown that administering IL-6 to breast cancer cells amplifies the activity of androgen receptors.

In all, the storyline of this paper suggests the following: obesity leads to inflammation; inflammation is associated with higher levels of IL-6; IL-6 sensitizes androgen receptors; sensitized androgen receptors amplify growth signals that drive breast cancer even in an environment of low estrogen availability. ( Xagena )

Source: Colorado University, 2017

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