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

Overview

Journal Breast Cancer Res

Specialty Oncology

Date 2017 Aug 31

PMID 28851415

Citations 7

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Clinicopathological Factors and Interleukin-6 Levels Associated With Low Relative Dose Intensity in Women With Breast Cancer Receiving First-Line Chemotherapy.

Hutajulu S, Astari Y, Ucche M, Paramita D, Witaningrum R, Asdie R World J Oncol. 2024; 15(6):942-949.

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Development of predictive models for pathological response status in breast cancer after neoadjuvant therapy based on peripheral blood inflammatory indexes.

Liu S, Jiang C, Wu D, Zhang S, Qiao K, Yang X BMC Womens Health. 2024; 24(1):560.

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Neoadjuvant chemotherapy for breast cancer: an evaluation of its efficacy and research progress.

Chen Y, Qi Y, Wang K Front Oncol. 2023; 13:1169010.

PMID: 37854685 PMC: 10579937. DOI: 10.3389/fonc.2023.1169010.

A Coagulation-Related Gene-Based Prognostic Model for Invasive Ductal Carcinoma.

Li J, Du J, Wang Y, Jia H Front Genet. 2021; 12:722992.

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Phase II study of neratinib in older adults with HER2 amplified or HER2/3 mutated metastatic breast cancer.

Yuan Y, Lee J, Yost S, Stiller T, Blanchard M, Padam S J Geriatr Oncol. 2021; 12(5):752-758.

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