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Association of Pre-chemotherapy Peripheral Blood Pro-inflammatory and Coagulation Factors with Reduced Relative Dose Intensity in Women with Breast Cancer

Abstract

Background: Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Chemotherapy efficacy depends on relative dose intensity (RDI), and an RDI < 85% is associated with worse overall survival. The pro-inflammatory (interleukin (IL)-6, C-reactive protein (CRP)) and coagulation factors (D-dimer) serve as biomarkers of aging. The purpose of this study is to determine if these biomarkers are associated with reduced RDI in women with stage I-III BC.

Methods: This study enrolled women with stage I-III BC. Prior to adjuvant or neoadjuvant chemotherapy, peripheral blood was collected for biomarker measurement. Dose reductions and delays were captured and utilized to calculate the RDI delivered. Univariate and multivariate analyses were performed to describe the association between pre-chemotherapy IL-6, CRP, and D-dimer levels and an RDI < 85%, controlling for relevant tumor and patient factors (age, stage, receptor status, chemotherapy regimen, and pre-chemotherapy physical function and comorbidity).

Results: A total of 159 patients (mean age 58 years, range 30-81, SD 11.3) with stage I-III BC were enrolled. An RDI < 85% occurred in 22.6% (N = 36) of patients and was associated with higher pre-chemotherapy IL-6 (OR 1.14, 95% CI 1.04-1.25; p = 0.006) and D-dimer (OR 2.32, 95% CI 1.27-4.24; p = 0.006) levels, increased age (p = 0.001), increased number of comorbidities (p = 0.01), and decreased physical function by the Medical Outcomes Survey Activities of Daily Living (ADL) Scale (p = 0.009) in univariate analysis. A multivariate model, including two biomarkers (IL-6 and D-dimer), age, ADL, BC stage, and chemotherapy regimen, demonstrated a significant association between the increased biomarkers and reduced RDI < 85% (OR 2.54; p = 0.04).

Conclusions: Increased pre-chemotherapy biomarkers of aging (IL-6 and D-dimer) are associated with reduced RDI (<85%). Future studies are underway to validate these findings.

Trial Registration: ClinicalTrials.gov, NCT01030250 . Registered on 3 November 2016.

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References
1.
Falandry C, Bonnefoy M, Freyer G, Gilson E . Biology of cancer and aging: a complex association with cellular senescence. J Clin Oncol. 2014; 32(24):2604-10. DOI: 10.1200/JCO.2014.55.1432. View

2.
Gross C, McAvay G, Guo Z, Tinetti M . The impact of chronic illnesses on the use and effectiveness of adjuvant chemotherapy for colon cancer. Cancer. 2007; 109(12):2410-9. DOI: 10.1002/cncr.22726. View

3.
Shayne M, Crawford J, Dale D, Culakova E, Lyman G . Predictors of reduced dose intensity in patients with early-stage breast cancer receiving adjuvant chemotherapy. Breast Cancer Res Treat. 2006; 100(3):255-62. DOI: 10.1007/s10549-006-9254-4. View

4.
Peterson M, Thompson D, Pieper C, Morey M, Kraus V, Kraus W . A Novel Analytic Technique to Measure Associations Between Circulating Biomarkers and Physical Performance Across the Adult Life Span. J Gerontol A Biol Sci Med Sci. 2015; 71(2):196-202. PMC: 4723660. DOI: 10.1093/gerona/glv007. View

5.
Sanoff H, Deal A, Krishnamurthy J, Torrice C, Dillon P, Sorrentino J . Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer. J Natl Cancer Inst. 2014; 106(4):dju057. PMC: 3982894. DOI: 10.1093/jnci/dju057. View