Epigenetic Aging Higher Among Breast Cancer Survivors Administered Chemotherapy

Older survivors of breast cancer who were exposed to chemotherapy had greater epigenetic aging, also called an “epigenetic clock,” compared to people without cancer, according to the results of a recent study published in ACS Journals.

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Epigenetic age is measured by the changes in DNA methylation patterns. Epigenetic age may be an important biomarker of biological age because it is linked to the chronological age of various tissues and cell types.

“Prior studies with [breast cancer] survivors have shown short-term increases in biological aging from before to up to 1 year posttreatment based on epigenetic measures,” the study authors wrote in the article. “No studies have examined epigenetic markers of aging in longer term cancer survivors (i.e., more than 1 year posttreatment).”

In 2010, investigators began an ongoing national, multisite study that used data from the Thinking and Living with Cancer (TLC) cohort, which included survivors of breast cancer aged 60 years and older, to understand the longer-term impact of cancer and cancer care on epigenetic measures of aging, along with other common concerns of the disease.

Data collected from the cohort would include the patients’ epigenetic ages before and after systemic therapies (i.e., chemotherapy, hormone therapy), and investigators then frequency-matched patients to controls who did not have breast cancer.

The team predicted that survivors of breast cancer would be biologically older and have faster rates of epigenetic aging; chemotherapy would be the biggest factor to accelerated biological aging; and there is a relationship between epigenetic aging with cognitive and physical function, largely due to chemotherapy. They also tested the epigenetic aging of White versus Black survivors to better understand life course experiences on aging.

Using 5 tools to measure epigenetic aging and DNA methylation, investigators observed that survivors were biologically older than controls across multiple epigenetic aging measures at least 24 to 36 months after enrollment. The biological aging of survivors could also last for up to 60 months after active therapy. For patients who received chemotherapy or radiotherapy, biological aging manifested as DNA damage and low telomerase levels that lasted for 3 to 6 years post-treatment.

Although chemotherapy was specifically associated with reduced cognitive function, older epigenetic age was generally associated with worse physical function in both survivors and controls.

Black survivors of breast cancer also showed a higher increase in epigenetic age than non-Hispanic White survivors. This lasted at least 60 months post-treatment and may reflect a difference in life course experiences that accelerate epigenetic aging.

Limitations of the study include limited sample size, decreased generalizability of findings as most patients received a high level of education and had relatively good health, underestimates of epigenetic aging, potential biases between arms, and not testing the impact of different treatment regimens on epigenetic aging.

Investigators noted that, “epigenetic aging may be modifiable by behavioral and pharmacological interventions…these preliminary results can also inform future studies testing whether biological aging markers might be clinically useful as early indicators of risk that can be used to tailor survivorship care.”

Reference

Rentscher K, Bethea T, Zhai W, et al. Epigenetic aging in older breast cancer survivors and non-cancer controls: preliminary findings from the Thinking and Living with Cancer (TLC) Study. ACS Journ. June 1,2023. doi: 10.1002/cncr.34818