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Large studies have consistently found that regular exercise is associated with a lower risk of developing breast cancer. But researchers have been at a loss to explain precisely how physical activity guards against cancer.

Researchers in the United States, however, think they have found the answer: Vigorous exercise makes estrogen less likely to trigger cancer or to fuel the growth of hormone-dependent tumours.

The lead researcher, Dr. Mindy Kurzer of the University of Minnesota, noted that scientists have long known some breast cancer tumours require estrogen to grow and contain specific receptors that will lock on to the hormone circulating in the bloodstream. Certain estrogen metabolites, or breakdown products, can also speed tumour growth, while others are relatively benign. In fact, earlier studies have hinted that women with higher levels of certain metabolites are at an elevated risk of getting cancer.

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So Kurzer, along with colleagues at the University of Pennsylvania, decided to investigate whether vigorous exercise could influence how estrogen is broken down in the body, as well as study the combination of metabolites that are produced as a result.

The researchers recruited more than 300 healthy, yet sedentary, women from 18 to 35 years old. Roughly half of them were randomly assigned to a vigorous exercise program of 30 minutes a day for five days a week. The other women served as a control group and continued with their sedentary lifestyle.

Urine samples were collected from the participants so researchers could measure levels of estrogen and estrogen metabolites.

"We have one of the few labs in the world that has the ability to analyze the full spectrum of estrogen metabolites – it is quite difficult to do," Kurzer said.

"Some of the breakdown products are very very benign – they act as weak estrogen and don't seem to do much when it comes to exerting biological effects. And some of them seem to be mutagenic, meaning they can damage the DNA and therefore are potentially carcinogenic."

She added there is "a whole series of different pathways by which estrogen can be broken down," leading to a very different mix of metabolites.

For the purposes of the study, the researchers focused on the ratio of two specific metabolites: 2-hydroxyestrone (2-OHE1) and 16 alpha-hydroxyestrone (16-alpha-OHE1).

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The metabolite 2-OHE1 is relatively benign with a weak estrogen effect. By contrast, 16-alpha-OHE1 is a potential menace. It acts as a strong estrogen and can bind irreversibly to estrogen receptors. "If estrogen is promoting a cancer, then this particular metabolite is going to be very effective at doing that job," Kurzer said. That metabolite is also considered potentially carcinogenic.

"So you would want to have more of the benign metabolite and less of the damaging one," Kurzer said. And that is what vigorous exercise seems to do.

After four months, the women in the exercise group had a much more favourable ratio of these two metabolites than the sedentary participants, according to the study published in the journal Cancer Epidemiology, Biomarkers & Prevention.

Kurzer noted that a lot more research is needed to flesh out the current finding. "There are so many more questions we could look at. Could some women benefit more than others with exercise? Or could you see a greater effect with additional activity?"

In the meantime, she hopes the study will encourage people to get off the couch and be active. "We know that exercise is great for heart health and maintaining body weight, but here is an additional benefit," she said. "I think a lot of people are afraid of cancer and feel helpless … Perhaps this is one thing they can do to lower the possibility of getting cancer."

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