Abstract P4-07-08: Age-related microRNAs and their biomarker potential in chemotherapy-treated older breast cancer patients
Authors: B Dalmasso, S Hatse, B Brouwers, A Laenen, L Berben, C Kenis, A Smeets, P Neven, P Schöffski, H Wildiers
Journal: Cancer Research (2017)

Abstract BD and SH contributed equally to this study. Background MicroRNAs (miRNAs) are important regulators of cellular function and have been associated with both aging and cancer, while the impact of chemotherapy on miRNAs has barely been studied. Patients and Methods To examine whether chemotherapy accelerates the aging process, we have monitored age-related circulating miRNAs in 89 older breast cancer patients (≥70y), receiving adjuvant chemotherapy (N= 46; chemo group, ChG) or no chemotherapy (N= 43; control group, CoG). Patients and associated blood samples belonged to the cohort of our recently published study (Brouwers et al., Oncotarget. 2016.) All patients underwent geriatric assessment at inclusion (T0), after 3 months (T1) and 1 year (T2). At each timepoint we analysed the serum expression of nine age-related miRNAs (miR-20a, miR-30b, miR-34a, miR-106b, miR-191, miR-301a, miR320b, miR374a, miR-378a). Our primary aim was to assess miRNA changes during the study period, including differences between groups. Secondary endpoints included association of microRNAs with: chronological age, clinical geriatric assessment parameters and aging biomarkers assessed in the above-mentioned study. We then investigated the predictive role of miRNAs at T0 on: decline in functionality and quality of life, toxicity and unexpected hospitalization during or after chemotherapy. We also performed clustering of patients according to specific miRNA signatures. Results Except for miR-106b, which appeared to behave slightly different in ChG compared to CoG, all other miRNAs underwent moderate fluctuations during the study course with no significant differences between both groups. Also within the older cohort, several age-related miRNAs significantly (p&amp;lt;0.05) correlated with clinical aging/frailty (miR-106b, miR-191, miR-301a, miR-320b, miR-374a), as well as with other biomarkers of aging. In particular, miR-106b, miR-374a and miR-378a were associated with IL-6 (slope= -0.34, -0.30 and 0.30 respectively, p&amp;lt;0.05), whereas miR-301a and miR-378a showed a relevant correlation with MCP-1 (slope= -0.18 and 0.27 respectively, p&amp;lt; 0.05). Moreover, based on their 'aging miRNA' profiles, patients clustered into two distinct groups, cluster A (CA) and cluster B (CB), exhibiting significantly different results for several biological/clinical aging parameters. CA (N=43, miR-20a, miR-30b, miR-191, miR-301a and miR-374a underexpressed, miR-378a overexpressed) was characterized by older age, higher geriatric risk profile, as well as elevated IL-6, TNFα and MCP-1 levels compared to CB (N=45, inverse expression pattern). Moreover, 31.9% of CA patients but only 7.4% of CB patients experienced decline in quality of life after chemotherapy (p=0.051). Conclusions These results further corroborate our recent findings, stating that adjuvant chemotherapy does not significantly boost aging progression in elderly breast cancer patients. Our data also endorsed specific age-related miRNAs as promising aging/frailty biomarkers in oncogeriatric populations. Citation Format: Dalmasso B, Hatse S, Brouwers B, Laenen A, Berben L, Kenis C, Smeets A, Neven P, Schöffski P, Wildiers H. Age-related microRNAs and their biomarker potential in chemotherapy-treated older breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-07-08.