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York research finds possible cause for poor response to treatment in obese breast cancer patients

A York University researcher has published a study in the Journal of Applied Physiology that identifies possible reasons why obese breast cancer patients have a poorer response to therapy and higher risk of death than their lean counterparts.

Michael Connor

Michael Connor

Michael Connor, associate professor of kinesiology and health science in the Faculty of Health, said for nearly 50 years researchers have been aware of an association between obesity and breast cancer, and he set out to determine the factors contributing to this relationship.

“The underlying reason behind this deleterious association remains poorly understood,” he said. “Compared to their lean counterparts, obese breast cancer patients have larger and more severe tumors, have a poorer response to therapy and are more likely to succumb to the disease.”

Connor and his research team looked at whether the fat cells themselves play a role in the harmful link between obesity and breast cancer, and whether interventions targeted at obesity can result in beneficial effects on the cancer itself.

For many years, said Connor, adipose tissue was thought of as simply a storage form of energy when calorie intake exceeds calorie output/need. However, fat cells have since been discovered to be active cells that produce more than 400 hormones that eventually end up in the blood and make their way around the body to exert their effects.

A breast cancer cell, photographed by a scanning electron microscope, which produces a 3-dimensional images (image: Wikimedia Commons)

A breast cancer cell, photographed by a scanning electron microscope, which produces a 3-dimensional images (image: Wikimedia Commons)

Although many of these hormones, termed adipokines, have effects on energy usage, there are some that have effects on cell growth as well.

Another factor to consider, he said, is that the relative production of these adipokines is different in an obese person compared to a lean person.

The research team set out to determine whether this difference in adipokine secretion from adipose tissue can account for the observed association between obesity and breast cancer, and to determine if exercise can be a beneficial way to counteract any of these deleterious obesity-associated breast cancer effects.

Observations of the research identified two of these adipokines – adiponectin (ADIPO) and leptin (LEP) – as potential candidates to mediate the obesity effects because: they are both produced in high abundance; each cause opposite effects on cancer cell growth (ADIPO prevents growth and LEP promotes growth); and they both change with obesity (ADIPO decreases and LEP increases).

“We show that the actions of these adipokines counteract each other and that obese adipose tissue can accentuate breast cancer growth because of this increase in LEP and decrease in ADIPO production,”said Connor.

“We also show that voluntary exercise can counteract and even completely prevent these obesity-dependent effects in a dose-dependent manner, with the greater the amount of exercise causing greater preventative effects on cancer growth.”

Connor said the research was successful in identifying possible candidates that cause obese breast cancer patients to be worse off than lean patients. The research also points to exercise – which has none of the harmful side effects that are associated with many cancer drugs – as being a potentially beneficial therapy for obese breast cancer patients.