A new study led by investigators at the UCLA Health Jonsson Comprehensive Cancer Center has revealed that common breast cancer treatments, including chemotherapy, radiation, and surgery, may accelerate the biological aging process in breast cancer survivors.
The findings, published in the Journal of the National Cancer Institute, show that markers of cellular aging-;such as DNA damage response, cellular senescence, and inflammatory pathways-;significantly increased in all breast cancer survivors, regardless of the type of treatment received. This suggests that the impact of breast cancer treatments on the body is more extensive than previously thought.
"For the first time, we're showing that the signals we once thought were driven by chemotherapy are also present in women undergoing radiation and surgery," said study lead author Judith Carroll, an associate professor of psychiatry and biobehavioral sciences at UCLA, Endowed Chair for the George F. Solomon Professorship in Psychobiology and investigator in the UCLA Health Jonsson Comprehensive Cancer Center.
While we expected to see increased gene expression linked to biological aging in women who received chemotherapy, we were surprised to find similar changes in those who only underwent radiation or surgery."
Judith Carroll, Associate Professor, Psychiatry and Biobehavioral Sciences, University of California - Los Angeles Health Sciences
Advances in cancer therapies have greatly improved survival rates, with an estimated 4 million breast cancer survivors in the U.S. today and over 6 million expected by 2040. However, breast cancer is linked to accelerated aging, impacting physical abilities, independence, and lifespan. Biological aging processes, which drive conditions like fatigue, cognitive decline, frailty, and cardiovascular disease, appear to be a major factor. Evidence suggests that cancer treatments, like chemotherapy, can increase the risk of earlier onset of these aging-related conditions, making it crucial to understand the specific pathways involved to better target and manage them.
To examine how gene expression related to aging changes over time in women diagnosed with breast cancer, the team conducted a two-year longitudinal study that tracked women undergoing breast cancer treatment prior to receiving treatment and again following treatment to see how their biological aging markers evolved.
The team tracked the gene expression in their blood cells using RNA sequencing, focusing on markers that signal biological aging -; including a process known as cellular senescence, which is when cells stop dividing but don't die. These so-called "zombie cells" accumulate over time and can release harmful substances that damage nearby healthy cells, contributing to aging and inflammation.
The data was then analyzed using statistical models to help identify aging-related changes.
The team found that regardless of treatment type there was an increase in expression of genes that track cellular processes involved in biological aging. Specifically, genes that capture cellular senescence and the inflammatory signal from these cells, indicating that their immune cells were aging faster than normal.
They also saw increases in DNA damage response genes, which are genes that are expressed when there is DNA damage. Although chemotherapy did have a slightly different pattern, similar to what others have shown, they also noted changes in women who did not receive chemotherapy.
"The results suggest women who receive treatment for breast cancer have a pattern of gene expression that indicates increased DNA damage and inflammation, which could be important targets for recovering from cancer and having a better quality of life in survivorship," said senior author of the study Julienne Bower, professor of psychology in the UCLA College and psychiatry and biobehavioral sciences and member of the UCLA Health Jonsson Comprehensive Cancer Center.
"We've only just begun to understand the long-term consequences of cancer therapy and these findings are a critical step toward understanding the biological pathways that drive many post-treatment symptoms in breast cancer survivors," added Carroll. "Our goal is to find ways to improve survivorship, not just in terms of years lived, but also in quality of life and overall health."
The team is now exploring a new biomarker that measures a woman's biological age and the pace at which she is aging. This could help determine whether the aging signals detected during cancer treatment have a long-term effect on biological age. The team plans to investigate factors that may influence this, with a focus on protective behaviors such as exercise, stress management and healthy sleep patterns.
Carroll and Bower also are affiliated the Cousins Center for Psychoneuroimmunology, and the Semel Institute for Neuroscience and Human Behavior at UCLA. Other UCLA authors include Catherine Crespi, Steve Cole, Patricia Ganz and Laura Petersen.
The study was supported by grants from the National Cancer Institute.
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