Researchers have found that common breast cancer treatments—including chemotherapy, radiation, and surgery—may accelerate the biological aging process among breast cancer survivors, according to a new study published by Carroll et al in the Journal of the National Cancer Institute. The findings suggested that the impact of breast cancer treatments on the body could be more extensive than previously considered.
Background
Advances in cancer therapy have successfully improved survival rates, with an estimated 4 million breast cancer survivors in the United States today and over 6 million expected by 2040.
However, breast cancer is linked to accelerated aging, impacting physical abilities, independence, and life span. Biological aging processes—which drive conditions like fatigue, cognitive decline, frailty, and cardiovascular disease—could be a major factor driving the association. Prior research has suggested 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 as well as better target and manage them.
Study Methods and Results
In the new study, the researchers examined how gene expression related to aging may change over time in women diagnosed with breast cancer. They conducted a 2-year longitudinal study tracking women undergoing breast cancer therapy prior to and following treatment to determine how their biological aging markers evolved.
The researchers tracked the gene expression in the patients’ blood cells using RNA sequencing, focusing on markers that signal biological aging such as cellular senescence, which occurs when cells stop dividing but don't die. These cells subsequently accumulate over time and can release harmful substances that damage nearby healthy cells, contributing to aging and inflammation. The researchers then analyzed the data using statistical models to help identify aging-related changes.
The researchers found that markers of cellular aging such as DNA damage response, cellular resistance, and inflammatory pathways increased in all of the patients involved in the study—regardless of the type of treatment they received. Further, there was an increase in the expression of genes tracking cellular processes involved in biological aging. Specifically, the researchers noted that the expression of genes responsible for capturing cellular senescence and the inflammatory signal from these cells increased, indicating that the patients’ immune cells were aging quicker than normal.
They also observed increases in DNA damage response genes. Although chemotherapy did have a slightly different pattern, the researchers reported changes in women who did not receive chemotherapy.
Conclusions
“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,” emphasized lead study author Judith Carroll, PhD, Associate Professor of Psychiatry and Biobehavioral Sciences at the University of California, Los Angeles (UCLA) and Endowed Chair of the George F. Solomon Professorship in Psychobiology at 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,” she added.
“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,” underscored senior study author Julienne Bower, PhD, Professor of Psychology as well as Psychiatry and Biobehavioral Sciences at UCLA and a member of the UCLA Health Jonsson Comprehensive Cancer Center.
The researchers are currently exploring a novel biomarker measuring biological age and the pace of aging. The research could help determine whether the aging signals detected during cancer treatment have a long-term effect on biological age. The researchers plan to investigate factors that may influence biological aging, with a focus on protective behaviors such as exercise, stress management, and healthy sleep patterns.
"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. 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," concluded Dr. Carroll.
Disclosure: The research in this study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit academic.oup.com.
