Association of pre-chemotherapy peripheral blood pro-inflammatory and coagulation factors with reduced relative dose intensity in women with breast cancer

Yuan Yuan, Nilesh Vora, Can-Lan Sun, Daneng Li, Enrique Soto-Perez-de-Celis, Joanne Mortimer, The-Hang Luu, George Somlo, James Waisman, David Smith, Joseph Chao, Vani Katheria, Timothy Synold, Vivi Tran, Shu Mi, Abrahm Levi, Anait Arsenyan, Jennifer Choi, Laura Zavala, Susan Yost, Arti Hurria, Yuan Yuan, Nilesh Vora, Can-Lan Sun, Daneng Li, Enrique Soto-Perez-de-Celis, Joanne Mortimer, The-Hang Luu, George Somlo, James Waisman, David Smith, Joseph Chao, Vani Katheria, Timothy Synold, Vivi Tran, Shu Mi, Abrahm Levi, Anait Arsenyan, Jennifer Choi, Laura Zavala, Susan Yost, Arti Hurria

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.

Keywords: Activities of Daily Living; Adjuvant; Aging; Biomarkers; Blood coagulation factors; Breast Cancer; Chemotherapy; Cytokines; Dose-response relationship; Drug; Neoadjuvant; Older adults.

Conflict of interest statement

Ethics approval and consent to participate

This prospective longitudinal study was open at two participating institutions (City of Hope and Long Beach Memorial Medical Center). The study was approved by the institutional review boards of both participating institutions. Participating patients completed the informed consent process.

Consent for publication

Not applicable.

Competing interests

I confirm that I have read BioMed Central's guidance on competing interests and have included a statement indicating that none of the authors have any competing interests in the manuscript.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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