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Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a.

Publication ,  Journal Article
Shachar, SS; Deal, AM; Reeder-Hayes, KE; Nyrop, KA; Mitin, N; Anders, CK; Carey, LA; Dees, EC; Jolly, TA; Kimmick, GG; Karuturi, MS; Speca, JC ...
Published in: JNCI Cancer Spectr
December 2020

BACKGROUND: Although 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. METHODS: We 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. 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). 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. 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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Published In

JNCI Cancer Spectr

DOI

EISSN

2515-5091

Publication Date

December 2020

Volume

4

Issue

6

Start / End Page

pkaa082

Location

England

Related Subject Headings

  • 3211 Oncology and carcinogenesis
 

Citation

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MLA
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Shachar, S. S., Deal, A. M., Reeder-Hayes, K. E., Nyrop, K. A., Mitin, N., Anders, C. K., … Muss, H. B. (2020). Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a. JNCI Cancer Spectr, 4(6), pkaa082. https://doi.org/10.1093/jncics/pkaa082
Shachar, Shlomit S., Allison M. Deal, Katherine E. Reeder-Hayes, Kirsten A. Nyrop, Natalia Mitin, Carey K. Anders, Lisa A. Carey, et al. “Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a.JNCI Cancer Spectr 4, no. 6 (December 2020): pkaa082. https://doi.org/10.1093/jncics/pkaa082.
Shachar SS, Deal AM, Reeder-Hayes KE, Nyrop KA, Mitin N, Anders CK, et al. Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a. JNCI Cancer Spectr. 2020 Dec;4(6):pkaa082.
Shachar, Shlomit S., et al. “Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a.JNCI Cancer Spectr, vol. 4, no. 6, Dec. 2020, p. pkaa082. Pubmed, doi:10.1093/jncics/pkaa082.
Shachar SS, Deal AM, Reeder-Hayes KE, Nyrop KA, Mitin N, Anders CK, Carey LA, Dees EC, Jolly TA, Kimmick GG, Karuturi MS, Reinbolt RE, Speca JC, Muss HB. Effects of Breast Cancer Adjuvant Chemotherapy Regimens on Expression of the Aging Biomarker, p16INK4a. JNCI Cancer Spectr. 2020 Dec;4(6):pkaa082.

Published In

JNCI Cancer Spectr

DOI

EISSN

2515-5091

Publication Date

December 2020

Volume

4

Issue

6

Start / End Page

pkaa082

Location

England

Related Subject Headings

  • 3211 Oncology and carcinogenesis