Study Finds Chemotherapy Accelerates Molecular Aging in Patients With Breast Cancer
Physicians have long suspected that chemotherapy can accelerate the aging process in patients treated for cancer. Using a test developed at UNC Lineberger Comprehensive Cancer Center to determine molecular aging, oncologists have directly measured the impact of anticancer chemotherapy drugs on biological aging. The study by Sanoff et al was published in the Journal of the National Cancer Institute.
Study Details
Researchers measured the level of p16, a protein that causes cellular aging, in the blood of 33 women over the age of 50 who had undergone chemotherapy for curable breast cancer. Samples were taken for analysis of molecular age from patients before chemotherapy, immediately following chemotherapy, and a year after therapy finished. The analysis showed that curative chemotherapy also caused an increase in a patient’s molecular age that on average was equivalent to 15 years of normal aging. The same was true in a separate group of 176 breast cancer survivors who had received chemotherapy on average 3.5 years prior.
Hanna Sanoff, MD, Assistant Professor at the UNC School of Medicine and member of UNC Lineberger said that the results indicate that the p16 test holds promise as a means of evaluating how chemotherapy will affect a patient’s long-term health and survival and as a predictive biomarker for the long-term toxicity of chemotherapy.
Role of p16
“Our theory is that if you have an advanced molecular age to begin with, it will be harder for you to tolerate chemotherapy,” said Dr. Sanoff. “We believe a high level of p16 before treatment could mean that a patient will have a harder time making new blood cells after each chemotherapy treatment, and therefore be at greater risk for anemia and infection during chemotherapy.”
The key role of p16 in human aging has been established over the last decade in the lab of Norman E. Sharpless, MD, Director of UNC Lineberger. Research conducted in Dr. Sharpless’ lab showed in 2004 that the levels of p16 increase exponentially with aging, and developed the p16 blood test for human use in 2009.
Next Steps
The next direction for this research, ongoing under the leadership of Hyman B. Muss, MD, Director of UNC Lineberger’s Geriatric Oncology Program, involves determining if markers of molecular age predict patients’ physical function and outcome in a number of clinical settings.
“While these findings are highly provocative, we have much more to study and will have to verify in future trials how these changes in molecular aging affect long term survival,” said Dr. Muss. “Adjuvant chemotherapy has dramatically improved breast cancer survival and pending further data, the results of our study should not effect adjuvant chemotherapy decisions.”
Drs. Muss and Sharpless are the corresponding authors for the Journal of the National Cancer Institute article.
This research was supported by grants from the National Institutes of Health, the Paul Glenn Foundation, the Burroughs Wellcome Fund, and the Breast Cancer Research Foundation. UNC holds a patent on the diagnostic test of molecular aging. The lead study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
