Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16 INK4a

• Published in: JNCI cancer spectrum Vol. 4; no. 6; p. pkaa082
• Main Authors: Shachar, Shlomit S, Deal, Allison M, Reeder-Hayes, Katherine E, Nyrop, Kirsten A, Mitin, Natalia, Anders, Carey K, Carey, Lisa A, Dees, E Claire, Jolly, Trevor A, Kimmick, Gretchen G, Karuturi, Meghan S, Reinbolt, Raquel E, Speca, JoEllen C, Muss, Hyman B
• Format: Journal Article
• Language: English
• Published: England 01.12.2020
• ISSN: 2515-5091

Although chemotherapy saves lives, increasing evidence shows that chemotherapy accelerates aging. We previously demonstrated that mRNA expression of , 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 expression vary by chemotherapy regimen among early stage breast cancer patients. We conducted a study of stage I-III breast cancer patients receiving adjuvant or neoadjuvant chemotherapy. expression was analyzed prechemotherapy and postchemotherapy (median 6.2 months after the last chemotherapy) in peripheral blood T lymphocytes. Chemotherapy-induced change in expression was compared among regimens. All statistical tests were 2-sided. In 146 women, chemotherapy was associated with a statistically significant increase in expression (accelerated aging of 17 years; < .001). Anthracycline-based regimens were associated with the largest increases (accelerated aging of 23 to 26 years; ≤ .008). Nonanthracycline-based regimens demonstrated a much smaller increase (accelerated aging of 9 to 11 years; ≤ .15). In addition to the type of chemotherapy regimen, baseline levels, but not chronologic age or race, were also associated with the magnitude of increases in . Patients with lower levels at baseline were more likely to experience larger increases. Our findings suggest that the aging effects of chemotherapy may be influenced by both chemotherapy type and the patient's baseline level. Measurement of expression is not currently available in the clinic, but nonanthracycline regimens offering similar efficacy as anthracycline regimens might be favored.