WASHINGTON — Chemotherapy helps many women survive breast cancer, but new research suggests that chemotherapy may also accelerate biological aging beyond chronological age and increase the risk of earlier death from other causes. The findings point to a need to explore whether interventions to slow or reverse biological aging could improve long-term health for breast cancer survivors.
The study, by researchers at Georgetown University's Lombardi Comprehensive Cancer Center and colleagues, appeared November 10, 2026, in JAMA Open Network . This research is the first to estimate the lifetime balance of the benefits of curing breast cancer versus possible acceleration of biological aging using population-based simulation modeling.
"Female breast cancer survivors comprise the single largest segment of the 18.6 million cancer survivors in the United States. However, some forms of chemotherapy that extend survival have triggered a secondary crisis: treatment-induced molecular damage to the body's cells and organs, causing acceleration of biological age," says the study's senior author, Jeanne Mandelblatt, MD, MPH, director of the Georgetown Lombardi's Institute for Cancer and Aging Research (I-CARE). "Chemotherapy-induced biologic aging can persist for years, and the effects of this acceleration are not visible for many years."
She notes that this accelerated biological aging can result in loss of healthy life years due to earlier onset of aging diseases and conditions like frailty and cognitive problems.
"The key to our methodology is accounting for the fact that while chemotherapy improves breast cancer survival, treatment can also increase damage to normal tissues. This affects many aging systems, including increasing the number of senescent cells, which are damaged cells that have stopped dividing and are also resistant to cell death," explains Swarnavo Sarkar, PhD, lead author and a member of I-CARE at Lombardi. "Senescent cells secrete biological molecules that cause several aging-related diseases through added tissue damage and inflammation."
The investigators used data about the relationships between chemotherapy and blood levels of the p16 protein, a common biomarker of senescence, to estimate the biological age of breast cancer survivors over their remaining lives. The p16 protein levels were used for this study because there is good data from published research and there is evidence from the lab that clearing p16-rich cells could increase their lifespan. There are also evolving studies of other biological aging markers that could be used in future studies.
The population simulation model the researchers developed was based on women who were 30 to 79 years of age; the model compared the effects of types of chemotherapy that caused more vs. less cellular damage (i.e., cytotoxic) and biological age acceleration. Those who received the most cytotoxic regimens were estimated to have lost 9.4 remaining life years on average due to earlier onset of aging-related diseases.
While treatment choices will always be based on the potential to cure, Mandelblatt hopes that the model results can be used to guide future studies evaluating the benefits of testing biological age after treatment ends. The goal would be to provide personalized survivorship care to mitigate any aging effects of therapy and improve quality of life and health over a survivor's lifetime. This is particularly salient now, she notes, since physical activity and medications being used for other purposes show promise in slowing accelerated aging in breast and other cancer survivors, which may recoup the loss of life years estimated in this study.
The data analysis was possible because both Mandelblatt and Sarkar are members of CISNET (Cancer Intervention and Surveillance Modeling Network), a 25-year-old consortium of National Cancer Institute-sponsored investigators who use simulation modeling to improve the understanding of cancer prevention, screening, and treatment and their effects on population trends in incidence and mortality.
"There are two next steps we are planning, the first being expanding the scope of this methodology for other types of breast cancer treatments, such as radiotherapy, immunotherapies, targeted therapies and hormonal treatments, which also appear to speed up aging, with effects potentially lasting for many years after treatment," concludes Sarkar. "We also plan to include information about survivor characteristics to help guide future conversations about individual outcomes."
