How inherited fitness may affect breast cancer risk

Repeated studies have shown that physical inactivity and related obesity raise the risk of many chronic diseases, including breast cancer and other cancers.

In fact, the evidence is so compelling that lifestyle guidelines from most health agenciesboth in the United States and abroad, include recommendations for preventing obesity by maintaining a fit weight for height and physically active lifestyle.

But what if the science behind these recommendations was only half the story? What if your fitness was influenced not only by your activity level but also by your genes? And, focusing specifically on breast cancer, what if your risk of breast cancer depended on your inherited fitness level?

A team of researchers, including myself, investigated these issues in a recently published paper test and discovered a surprisingly huge role for genetics in physical fitness and breast cancer.

Are you in your best shape?

We often associate a physically busy lifestyle and maintaining a fit weight for a given height (measured by body mass index) with physical fitness, which is sometimes referred to as cardiorespiratory fitness. And people with People with high physical fitness usually cope better not only in lower risk of chronic diseases such as cancer. Even when diagnosed and treated, they have a more favorable forecast for recovery purposes.

However, it is commonly overlooked that aerobic fitness, broadly defined as the ability to transport oxygen and nutrients to the muscles, has hereditary component. This explains why people following the same training program have a wide range of improvements in their physical fitness in response to the same amount of exercise.

This inherited ability to stay physically fit made us wonder whether it affects the risk of developing breast cancer.

Our question, while elementary, would be hard to study in humans because it would require a lifetime of sedentary behavior, which is at odds with medical recommendations for health and well-being. So the team decided to investigate this question in the lab. We worked to isolate the effects of innate fitness and then studied how they affected breast cancer rates.

The fitness model was developed by selecting rats over multiple generations with either low or high treadmill running activity. The rats that ran the furthest distance before fatigue were bred to each other, and the rats that fatigued from running early were also bred. This procedure was repeated over multiple generations, ultimately producing pups with huge differences in inherited fitness.

To investigate the effects of these differences in innate fitness, we took female puppies born to high- or low-fitness mothers and kept the puppies so that we could assess primarily the fitness effects related to genetics rather than exercise. Before reaching puberty, the puppies were exposed to a chemical that triggers the development of breast cancer.

The animals were then monitored for palpable tumors throughout their lives, and for tumors too diminutive to detect without a magnifying glass at the time of their death. What we found was striking.

Born able-bodied and disabled

Rats born with low physical fitness were four times more likely breast cancer, whereas rats born with high fitness not only had lower rates of tumor development, but the tumors appeared later in life and were smaller.

These effects have been attributed, at least in part, to a network of sensors found in virtually every cell in the body.

This system, called mammalian targets of rapamycinsenses the availability of energy and various nutrients in the cell. When energy and nutrient availability are high, the system is busy and promotes the cell’s ability to proliferate; excessive cell division is a hallmark of cancer.

We found that mammary cell signaling activity was high in rats born with low fitness, whereas it was reduced in rats born with high fitness.

Attempts to identify hormones or growth factors in the blood that might explain this difference have been unsuccessful, suggesting that the responses come from deep within the cell.

Next Steps: Moving from Lab to Clinic

An increasing number of studies conducted among women have shown a link between exercise and breast cancer riskand these findings seem to indicate that aerobic capacity changes the internal functioning of cells, providing them with protective properties.

However, our study suggests that there is an innate protective element that influences exercise performance as well as breast cancer risk.

Many questions were raised by this study. Recognizing that our experiment was conducted on rodents and that rodents are not humans, the stage was set for extending these observations from the laboratory to the clinic.

Much work remains to be done in rats with low and high innate fitness. Current research is focused on how to reduce the risk of breast cancer in rats born with low fitness. Key questions include determining the amount and type of exercise needed to break the link between low innate fitness and the development of breast cancer, since most of us have the ability to raise our innate fitness with exercise.