Exercise’s Cognitive Benefits in Breast Cancer Survivors May Vary by Aging and Neighborhood Factors

At the 51st Annual Oncology Nursing Society (ONS) Congress, Myeong-ga Cho, MSN, RN, of the University of Pittsburgh, presented findings from the EPICC trial examining how aerobic exercise, neighborhood deprivation and epigenetic aging may influence cognitive outcomes in postmenopausal women with breast cancer.

The study, titled “Linking Aerobic Exercise, Area Deprivation, Epigenetic Age Acceleration, and Cognition in Postmenopausal Women with Breast Cancer: Results from EPICC Trial,” explored whether biological aging and socioeconomic factors may alter patients’ cognitive responses to exercise interventions.

Examining Cognitive Decline in Breast Cancer Survivors

Postmenopausal women with breast cancer commonly experience cognitive impairment during and after treatment, often referred to as cancer-related cognitive decline. Investigators sought to better understand how environmental and biological factors may contribute to these changes.

“Cancer and cancer treatment may cause faster biological aging, and that aging may harm cognitive health,” Cho explained during the presentation. “Biological age and chronological age do not always match, and some people age faster. We call this accelerated aging, and those on accelerated trajectory face compounding health risks, including cognitive decline.”

The study evaluated relationships among aerobic exercise, area deprivation, epigenetic age acceleration and objectively measured cognition in women enrolled in the EPICC randomized controlled trial (NCT02793921).

Researchers analyzed data from 116 postmenopausal women with breast cancer who were randomly assigned to either a 6-month aerobic exercise intervention or usual care. Participants had a mean age of 62.4 years, 90% were White and 61% had stage I disease.

Area Deprivation Associated With Accelerated Biological Aging

Investigators used the Area Deprivation Index (ADI), a national percentile ranking in which higher scores indicate greater neighborhood disadvantage, to assess socioeconomic deprivation. Findings showed that higher ADI scores were associated with greater epigenetic age acceleration at baseline using both PhenoAge and BrainAge methylation clocks.

Cho noted that “women in more deprived areas were not just aging more quickly, not just accumulated age, but in their active rate of aging.”

The authors noted that these findings suggest neighborhood-level socioeconomic stressors may contribute to accelerated biological aging in breast cancer survivors.

Although aerobic exercise did not significantly improve epigenetic age acceleration overall compared with usual care, exercise appeared to produce greater benefit among participants living in less deprived neighborhoods, particularly when assessed using BrainAge measures.

“So socioeconomic environment may shape the extent to which women benefit on their biological aging from exercise,” Cho said.

Cognitive Responses Varied Across Epigenetic Aging Measures

The study also demonstrated complex relationships between epigenetic age acceleration and cognitive performance.

Mental flexibility was positively associated with both baseline GrimAge acceleration and changes in PhenoAge acceleration over time. Additionally, participants with greater baseline epigenetic age acceleration showed differing cognitive responses to aerobic exercise depending on the cognitive domain evaluated.

Among women with higher baseline Horvath1 and GrimAge acceleration, those assigned to aerobic exercise experienced less improvement in verbal memory compared with usual care. However, greater baseline epigenetic age acceleration based on Horvath1, Horvath2 and Hannum clocks was associated with greater improvement in attention among women in the aerobic exercise group.

According to investigators, these findings indicate that biological aging may influence which patients derive cognitive benefit from exercise interventions and which domains of cognition are most affected.

Cho explained that epigenetic clocks are increasingly being used to measure these effects because “DNA methylation is the most rigorous indicator of biological aging currently.”

Implications for Precision Supportive Care

The authors concluded that area deprivation and epigenetic age acceleration may jointly shape cognitive responses to aerobic exercise in postmenopausal women with breast cancer.

Researchers suggested that cancer- and treatment-related physiologic stress may accelerate biological aging and potentially alter patients’ capacity to benefit from exercise-based supportive care interventions.

“The hypothesis is that exercise may improve cognition partly through decreasing accelerated aging,” Cho said. “However, a critical gap remains. We do not know how exercise and area deprivation jointly influence biological age acceleration and cognitive function.”

The findings may help identify subgroups of patients most likely to benefit from targeted cognitive interventions and support the development of more individualized supportive oncology care strategies.

References

Cho MG. Linking Aerobic Exercise, Area Deprivation, Epigenetic Age Acceleration, and Cognition in Postmenopausal Women with Breast Cancer: Results from EPICC Trial. Presented at: 51st Annual Oncology Nursing Society Congress; 2026.