Chemotherapy for Breast Cancer May Accelerate Biological Aging, Modeling Study Finds

Female breast cancer survivors make up the single largest group among the 18.6 million cancer survivors living in the United States. A new modeling study suggests that for many of them, the treatment that saved their lives may also be quietly speeding up the aging of their bodies.

The research comes from Georgetown University's Lombardi Comprehensive Cancer Center and colleagues, and was published in JAMA Network Open. Its authors describe it as the first to use population-based simulation modeling to estimate the lifetime balance between the benefit of curing breast cancer and the possible cost of accelerated biological aging.

The central idea is that chemotherapy, while it extends survival, also damages normal tissue. One consequence is a rise in senescent cells, which are damaged cells that have stopped dividing and resist cell death. Swarnavo Sarkar, the study's lead author and a member of Lombardi's Institute for Cancer and Aging Research (I-CARE), explains that these cells release biological molecules that add tissue damage and inflammation, and so contribute to several diseases associated with aging.

Jeanne Mandelblatt, the study's senior author and director of I-CARE, says the effects can persist for years and are not visible for many years after treatment. She notes that the practical result can be lost years of healthy life, as conditions such as frailty and cognitive problems arrive earlier than they otherwise would.

To build the model, the team used published data on how chemotherapy relates to blood levels of p16, a protein commonly used as a marker of senescence. They chose p16 because good published data exist for it, and because laboratory evidence indicates that clearing p16-rich cells could lengthen lifespan. The researchers note that other markers of biological aging are still being studied and could be used in later work. Using the p16 relationships, they estimated survivors' biological age across the rest of their lives.

The simulation covered women aged 30 to 79 and compared chemotherapy regimens that cause more cellular damage, termed more cytotoxic, with those that cause less. Women who received the most cytotoxic regimens were estimated to lose 9.4 remaining life years on average, owing to earlier onset of aging-related disease.

Mandelblatt stresses that treatment decisions will continue to be driven by the chance of cure. Her hope is that the model will guide future studies of whether testing biological age after treatment ends could support personalized survivorship care, aimed at limiting aging effects and improving health and quality of life over a survivor's lifetime. She adds that the timing is notable: physical activity and medications already used for other conditions are showing promise in slowing accelerated aging in breast and other cancer survivors, which may recover some of the life years the study estimates are lost.

The analysis was possible because both Mandelblatt and Sarkar belong to CISNET, the Cancer Intervention and Surveillance Modeling Network, a 25-year-old consortium of National Cancer Institute-sponsored investigators who use simulation to study cancer prevention, screening and treatment and their effects on incidence and mortality trends.

Sarkar says two next steps are planned. The first is extending the method to other breast cancer treatments, including radiotherapy, immunotherapies, targeted therapies and hormonal treatments, which also appear to speed aging, possibly for many years afterward. The second is adding survivor characteristics to the model to inform future conversations about individual outcomes.