Abstract
BackgroundChemotherapy 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.MethodsThis 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).ResultsA 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).ConclusionsIncreased 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 registrationClinicalTrials.gov, NCT01030250. Registered on 3 November 2016.
Highlights
Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity
The efficacy of chemotherapy is dependent on relative dose intensity, which is defined as the ratio of standard or planned dose intensity to actual dose intensity received
Growing evidence has demonstrated that pro-inflammatory and coagulation factors such as interleukin-6 (IL-6) [12,13,14], C-reactive protein (CRP) [12], and D-dimer may serve as potential biomarkers of aging
Summary
Chemotherapy decreases the risk of relapse and mortality in early-stage breast cancer (BC), but it comes with the risk of toxicity. Growing evidence has demonstrated that pro-inflammatory and coagulation factors such as interleukin-6 (IL-6) [12,13,14], C-reactive protein (CRP) [12], and D-dimer may serve as potential biomarkers of aging Elevated levels of these factors have been associated with reduced physical performance [15], frailty [16], and an increased risk of death [17] in communitydwelling older adults. The utility of these markers as predictors of chemotherapy tolerance, and the ability to deliver chemotherapy (i.e. RDI) in patients with breast cancer is unknown
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