Epigenetic aging in older breast cancer survivors and noncancer controls: preliminary findings from the Thinking and Living with Cancer Study

Abstract

Background

Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes.

Methods

Nonmetastatic breast cancer survivors ( n = 89) enrolled prior to systemic therapy and frequency‐matched controls ( n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age [EEA], PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy‐Cognitive Function) and physical (Medical Outcomes Study Short Form‐12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed‐effects models tested survivor‐control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve.

Results

Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures ( p = .001–.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older ( p = .001–.04), and among this group, an older EEA related to worse self‐reported cognition ( p = .047) relative to controls. An older epigenetic age related to worse physical function in all women ( p < .001–.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non‐Hispanic White survivors.

Conclusion

Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.

Abstract

Older breast cancer survivors were biologically older than matched noncancer controls across multiple epigenetic aging measures at 24 months or more after enrollment (which was presystemic therapy for survivors). Older breast cancer survivors who had received chemotherapy showed the greatest epigenetic aging, and among this group, an older epigenetic age was associated with worse self‐reported cognition relative to controls.