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Abstract
BackgroundAlthough chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging. We previously demonstrated that mRNA expression of p16INK4a, a biomarker of senescence and molecular aging, increased early and dramatically after beginning adjuvant anthracycline-based regimens in early stage breast cancer patients. Here, we determined if changes in p16INK4a expression vary by chemotherapy regimen among early stage breast cancer patients.MethodsWe conducted a study of stage I-III breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. p16INK4a expression was analyzed prechemotherapy and postchemotherapy (median 6.2 months after the last chemotherapy) in peripheral blood T lymphocytes. Chemotherapy-induced change in p16INK4a expression was compared among regimens. All statistical tests were 2-sided.ResultsIn 146 women, chemotherapy was associated with a statistically significant increase in p16INK4a expression (accelerated aging of 17 years; P < .001). Anthracycline-based regimens were associated with the largest increases (accelerated aging of 23 to 26 years; P ≤ .008). Nonanthracycline-based regimens demonstrated a much smaller increase (accelerated aging of 9 to 11 years; P ≤ .15). In addition to the type of chemotherapy regimen, baseline p16INK4a levels, but not chronologic age or race, were also associated with the magnitude of increases in p16INK4a. Patients with lower p16INK4a levels at baseline were more likely to experience larger increases.ConclusionsOur findings suggest that the aging effects of chemotherapy may be influenced by both chemotherapy type and the patient’s baseline p16INK4a level. Measurement of p16INK4a expression is not currently available in the clinic, but nonanthracycline regimens offering similar efficacy as anthracycline regimens might be favored.
Highlights
Chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging
We previously reported rapid and persistent increases in p16INK4a mRNA expression in the peripheral blood T cells in a small cohort of women receiving anthracycline-based adjuvant chemotherapy for early stage breast cancer, whereas in a second cohort of early stage breast cancer patients who did not receive chemotherapy, p16INK4a expression levels were similar to healthy volunteers [29]
We have previously shown that anthracycline-based chemotherapy in women with early stage breast cancer induced expression of cell senescence biomarkers in vivo [29]
Summary
Chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging. We previously demonstrated that mRNA expression of p16INK4a, a biomarker of senescence and molecular aging, increased early and dramatically after beginning adjuvant anthracycline-based regimens in early stage breast cancer patients. We determined if changes in p16INK4a expression vary by chemotherapy regimen among early stage breast cancer patients. Results: In 146 women, chemotherapy was associated with a statistically significant increase in p16INK4a expression (accelerated aging of 17 years; P < .001). Anthracycline-based regimens were associated with the largest increases (accelerated aging of 23 to 26 years; P .008). Nonanthracycline-based regimens demonstrated a much smaller increase (accelerated aging of 9 to 11 years; P .15). Conclusions: Our findings suggest that the aging effects of chemotherapy may be influenced by both chemotherapy type and the patient’s baseline p16INK4a level. Measurement of p16INK4a expression is not currently available in the clinic, but nonanthracycline regimens offering similar efficacy as anthracycline regimens might be favored
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