Breast cancer survivors who maintain an exercise routine suited to their personal needs may improve their long-term survival, a new study suggests.

The study, designed as a so-called target trial emulation, estimated that breast cancer survivors who start exercising regularly could see a reduction in their mortality risk over the next decade — up to 8 percentage points lower than if they simply received health-education materials.

Experts who were not involved in the study said the findings, published in JAMA Network Open, strengthen the case for physical activity after a breast cancer diagnosis. Previous research has already shown that exercise may bring women more immediate benefits, including helping them manage symptoms and treatment side effects.

“At the end of the day, if we start treating exercise as something that can truly impact survival, not just quality of life, it’s much more likely to become part of routine practice,” said Yara Abdou, MD, a breast cancer oncologist at the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina.

Emulating a Clinical Trial

Previous studies of patients with other cancer types have pointed to long-term survival benefits from exercise, including the recent randomized controlled CHALLENGE trial. It showed that for patients with colon cancer, a structured exercise program begun soon after adjuvant chemotherapy extended 5-year disease-free survival compared with health education. It also lowered all-cause mortality by 7 percentage points.

When it comes to breast cancer, numerous observational studies have suggested that postdiagnosis exercise can extend women’s lives. But clinical trial evidence is lacking.

For the new study, researchers led by Jinani Jayasekera, PhD, of the National Institutes of Health in Bethesda, Maryland, designed a target trial emulation — where observational data are used to approximate outcomes of a randomized controlled trial.

The researchers drew data from the Pathways Study, a prospective cohort of women in the Kaiser Permanente Northern California system who were diagnosed with stage I-III breast cancer between 2005 and 2013, with follow-up through 2021.

The researchers’ initial target trial, which was designed to emulate the CHALLENGE trial, included 959 women with stage II or III disease. A second, expanded analysis of 2107 women included those with stage I disease.

The initial analysis assumed women met the aerobic exercise goals of the CHALLENGE trial. The expanded analysis allowed more room for hypothetical tailored exercise strategies, in which participants gradually increased their weekly activity levels, with the option to modify or stop based on serious health conditions or swelling that interferes with exercise.

In the first analysis, the estimated 8-year risk for all-cause mortality was 23.7% vs 15.8% for women who received health education vs structured exercise. That absolute difference of 8 percentage points was on par with the benefit seen in the CHALLENGE trial.

In the expanded analysis, the estimated 10-year risk for all-cause mortality was 21.2% with no intervention. That was reduced to 18.1% with a strategy in which women boosted their weekly exercise levels by 60 minutes of vigorous activity or 120 minutes of moderate activity. Estimated breast cancer-specific mortality was 10% vs 7.6%.

Lesser increases in activity were associated with smaller but consistent reductions in risk.

‘Compelling’ Evidence, With Caveats

Abdou called the findings “very encouraging.”

“What makes [this study] especially compelling,” she said, “is that the results are consistent with what we’ve seen in randomized data from other cancers, and it includes a broad group of breast cancer survivors, including those with early-stage disease.”

Still, Abdou said, despite the trial emulation design, the data still come with the limitations of observational studies, including a reliance on self-report.

In addition, she noted, the study group may not fully reflect the broader population of women with breast cancer because they were all part of a single integrated health system.

Anne McTiernan, MD, PhD, of the Fred Hutchinson Cancer Center in Seattle, agreed that the study design is not a substitute for a clinical trial.

At the same time, she said, it would take randomized trials many years to get solid answers on the types, frequency, and duration of exercise it takes to extend breast cancer survivors’ lives. And that will probably not happen.

“The good news,” McTiernan said, “is that other trials have found exercise benefits to quality of life and symptoms associated with cancer and treatments. So women do not have to wait for a definitive trial that is unlikely to happen.”

Encouraging, Not Prescribing, Exercise

To Abdou, the findings support a simple message around physical activity.

“The way I would frame it to patients is, ‘Start where you are and aim to gradually do a little more over time,’” she said.

Patients should be assured, Abdou added, they don’t have to achieve a “fixed target” and can adjust their exercise levels based on how they feel, particularly during and soon after treatment.

“Exercise isn’t all or nothing,” she said, “and it doesn’t have to be intense to be beneficial.”

McTiernan suggested oncologists consider referring patients to established support services, such as the Moving Through Cancer program developed by the American College of Sports Medicine in Indianapolis.

“I believe that an oncologist’s referral to exercise programs, or just simple advice to women to keep an active lifestyle as their physical ability allows, would be great motivation to patients,” she said.

The study was funded by the National Institutes of Health. Abdou and McTiernan reported having no conflicts of interest.