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Age-related microRNAs in older breast cancer patients: biomarker potential and evolution during adjuvant chemotherapy.

ABSTRACT: BACKGROUND:MicroRNAs (miRNAs) are important regulators of cellular function and have been associated with both aging and cancer, but the impact of chemotherapy on age-related miRNAs has barely been studied. Our aim was to examine whether chemotherapy accelerates the aging process in elderly breast cancer patients using miRNA expression profiling. METHODS:We monitored age-related miRNAs in blood of women, aged 70 or older, receiving adjuvant chemotherapy (docetaxel and cyclophosphamide, TC) for invasive breast cancer (chemo group, CTG, n =?46). A control group of older breast cancer patients without chemotherapy was included for comparison (control group, CG, n =?43). All patients underwent geriatric assessment at inclusion (T0), after 3 months (T1) and 1 year (T2). Moreover, we analysed the serum expression of nine age-related miRNAs (miR-20a, miR-30b, miR-34a, miR-106b, miR-191, miR-301a, miR-320b, miR-374a, miR-378a) at each timepoint. RESULTS:Except for miR-106b, which behaved slightly different in CTG compared to CG, all miRNAs showed moderate fluctuations during the study course with no significant differences between groups. Several age-related miRNAs correlated with clinical frailty (miR-106b, miR-191, miR-301a, miR-320b, miR-374a), as well as with other biomarkers of aging, particularly Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1) (miR-106b, miR-301a, miR-374a-5p, miR-378a-3p). Moreover, based on their 'aging miRNA' profiles, patients clustered into two distinct groups exhibiting significantly different results for several biological/clinical aging parameters. CONCLUSIONS:These results further corroborate our earlier report, stating that adjuvant TC chemotherapy does not significantly boost aging progression in elderly breast cancer patients. Our findings also endorsed specific age-related miRNAs as promising aging/frailty biomarkers in oncogeriatric populations. TRIAL REGISTRATION:ClinicalTrials.gov, NCT00849758 . Registered on 20 February 2009. This clinical trial was registered prospectively.

SUBMITTER: Dalmasso B

PROVIDER: S-EPMC6196565 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Age-related microRNAs in older breast cancer patients: biomarker potential and evolution during adjuvant chemotherapy.

Dalmasso Bruna B Hatse Sigrid S Brouwers Barbara B Laenen Annouschka A Berben Lieze L Kenis Cindy C Smeets Ann A Neven Patrick P Schöffski Patrick P Wildiers Hans H

BMC cancer 20181022 1

<h4>Background</h4>MicroRNAs (miRNAs) are important regulators of cellular function and have been associated with both aging and cancer, but the impact of chemotherapy on age-related miRNAs has barely been studied. Our aim was to examine whether chemotherapy accelerates the aging process in elderly breast cancer patients using miRNA expression profiling.<h4>Methods</h4>We monitored age-related miRNAs in blood of women, aged 70 or older, receiving adjuvant chemotherapy (docetaxel and cyclophospha ...[more]

PMID: 30348127

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Project description:PurposePatients treated with adjuvant trastuzumab require adequate cardiac monitoring. We describe the patterns of cardiac monitoring and evaluate factors associated with adequate monitoring in a large population-based study of older patients with breast cancer.Patients and methodsPatients age 66 years or older with full Medicare coverage, diagnosed with stage I to III breast cancer between 2005 and 2009, and treated with adjuvant trastuzumab-based chemotherapy were identified in the SEER-Medicare and the Texas Cancer Registry-Medicare databases. The adequacy of cardiac monitoring was determined. Chemotherapy, trastuzumab use, cardiac monitoring, and comorbidities were identified by using International Classification of Diseases, 9th revision and Healthcare Common Procedure Coding System codes. Prescribing physician characteristics were also evaluated. Analyses included descriptive statistics and multilevel logistic regression models.ResultsIn all, 2,203 patients were identified; median age was 72 years. Adequate monitoring was identified in only 36.0% of the patients (n = 793). In the multivariable model, factors associated with optimal cardiac monitoring included a more recent year of diagnosis (hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54), anthracycline use (HR, 1.39; 95% CI, 1.14 to 1.71), female prescribing physician (HR, 1.37; 95% CI, 1.10 to 1.70), and physician graduating after 1990 (HR, 1.66; 95% CI, 1.29 to 2.12). The presence of cardiac comorbidities was not a determinant for cardiac monitoring. Of the variance in the adequacy of cardiac monitoring, 15.3% was attributable to physician factors and 5.2% to measured patient factors.ConclusionA large proportion of patients had suboptimal cardiac monitoring. Physician characteristics had more influence than measured patient-level factors in the adequacy of cardiac monitoring. Because trastuzumab-related cardiotoxicity is reversible, efforts to improve the adequacy of cardiac monitoring are needed, particularly in vulnerable populations.

Dataset Information

Age-related microRNAs in older breast cancer patients: biomarker potential and evolution during adjuvant chemotherapy.

Publications

Age-related microRNAs in older breast cancer patients: biomarker potential and evolution during adjuvant chemotherapy.

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