Cancer survivors who engage in strength training or other vigorous physical activity tend to live longer and have a lower risk of recurrence than those who don’t work out. A new study helps explain why.

There’s a lot of indirect evidence linking exercise to living longer with cancer. Women treated for breast cancer, for instance, who reported three or more hours per week of moderately intense activity after diagnosis had a 24 percent lower risk of breast cancer recurrence and a 34 percent lower risk of breast cancer death than their inactive counterparts. That’s according to a meta-analysis of six studies that together included more than 12,000 women.

But such observational studies can’t prove that exercise is the cause of the improved outcomes. And they can’t explain the mechanisms that could account for such an effect, or answer questions about the amount of exercise needed to gain any real protection.

Researchers at Oregon Health & Science University realized they could explore the issue more deeply using data they’d already gathered from three randomized, controlled trials designed for a different purpose: testing resistance training as way to limit functional decline after breast cancer treatment. (Those studies showed that breast cancer survivors can safely engage in a program of resistance and impact training to build muscle strength and prevent bone loss.)

“What we were able to do was go back and retrospectively look at biomarkers associated with cancer progression, cancer recurrence or mortality risk,” says first author Kerri Winters-Stone, co-leader of the Knight Cancer Institute’s Cancer Prevention and Control Program and the Elnora E. Thompson Distinguished Professor in the OHSU School of Nursing. The researchers published their findings this week in Cancer Epidemiology, Biomarkers & Prevention.

Winters-Stone and colleagues set out to test the hypothesis that exercise acts against cancer by lowering inflammation throughout the body and by improving the regulation of insulin signaling. Systemic inflammation and metabolic dysfunction are marked by elevations in several proteins that can be measured in blood, including insulin, C-reactive protein, leptin, interleukin 6 and others.

Related story: Exercise DVD helps women with breast cancer significantly improve fatigue symptoms

More than 250 women took part in the three clinical trials. In each study, participants were randomly assigned to a group receiving a resistance-training program or to a control group receiving a stretching and relaxation program. For both groups, the exercise routine consisted of two one-hour supervised classes and one 45-minute home-based session per week.

The training continued for one year, and the researchers measured changes in muscle strength, weight and body composition. They also were able to collect blood samples to examine for biomarkers of inflammation in 215 of the women at the outset of the study and after six and 12 months of training.

“Overall, women who engaged in resistance training reduced those inflammatory markers,” Winters-Stone says. “The effect was more pronounced among women who trained hard enough to gain muscle strength.”

Levels of C-reactive protein in blood declined by about 4 percent among the women in the resistance training groups, while this marker of inflammation increased by about 57 percent in the women in control groups. For the other blood biomarkers, there were no significant differences between resistance training and control groups until the study team dug a little deeper into the data.

“The effect was more pronounced among women who trained hard enough to gain muscle strength.”

The amount of benefit from exercise appeared to hinge on whether training was sufficient to produce gains in strength or reductions in body fat. Women with strength gains of 10 percent or more during the 12-month studies decreased CRP levels by 37 percent. Women in the resistance training group who lost weight saw a 31 percent reduction in C-reactive protein, and also a 30 percent reduction in leptin and a 28 percent reduction in serum amyloid A.

That’s consistent with several earlier observational studies, which found that the benefits of exercise on breast cancer recurrence and mortality only appear when women engage in a high level of physical activity, equivalent to 3 hours or more per week of moderate to vigorous physical activity.

The new study overcomes some key limitations of earlier efforts. It achieved a large sample size by combining three randomized trials that used the same type of resistance training program, avoiding the inconsistency in training modes in meta-analyses combining data from many studies. The 12-month training program in the new study is also among the longest of any trial of exercise and inflammation in breast cancer survivors, yielding reliable data on the long-term benefits of exercise.

Winters-Stone said the evidence on resistance training has reached a point where cancer care providers should do more to help patients – women and men – incorporate some form of exercise program into their treatment and recovery. Appropriately designed strength training, for instance, can slow bone loss, reverse muscle weakness, and prevent gains in body fat in men with prostate cancer undergoing androgen deprivation therapy.

While not all patients will be able to take on rigorous resistance training, more moderate exercise can be important. Studies have shown that physical activity programs are safe for cancer survivors and that they can produce improvements in fitness, strength, physical function, and cancer-related psychosocial variables. The new study bolsters the evidence that certain kinds of exercise training could also significantly increase survival.

“We have enough data now that we need to take it seriously,” Winters-Stone says.

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Further reading:

The Effects of Resistance Exercise on Biomarkers of Breast Cancer Prognosis: A Pooled Analysis of Three Randomized Trials by Kerri Winters-Stone, Lisa J. Wood, Sydnee Stoyles and Nathan Dieckmann. Cancer Epidemiology, Biomarkers & Prevention (November 15, 2017)

Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies by Ezzeldin M. Ibrahim and Abdelaziz Al-Homaidh. Medical Oncology (September 2011)