Abstract P6-01-07: Association of baseline pro-inflammatory (IL-6, CRP) and coagulation (D-dimer) markers with baseline functional status in women with breast cancer (BC) undergoing chemotherapy
Authors: Yuan Yuan , Vora Nilesh , Feng Tao , Mortimer Joanne , Luu Thehang , Somlo George , Chao Joseph , Tran Vivi , Mi Shu , Synold Tim , Waisman James , Zavala Laura , Katheria Vani , Hurria Arti 
Published: May 2015

Background: Pro-inflammatory and coagulation factors such as IL-6, CRP and D-dimer serve as biomarkers for aging. The utility of these markers as biologic correlates of physical function in patients with BC is not known. This study was performed to determine if baseline serum markers of inflammation (IL-6, CRP) and coagulation (D-dimer) correlate with baseline functional status in women with stage I-III BC requiring chemotherapy (chemo). Methods: This is a prospective longitudinal study that enrolled 153 women across all age groups with BC who had pre-chemotherapy peripheral blood captured for IL-6, CRP, and D-dimer and a baseline assessment of the following functional status measures: activities of daily living (Medical Outcomes Study [MOS] Physical Health); instrumental activities of daily living (IADL); self-rated Karnofsky performance status (KPS); physician-rated KPS; number of falls in last 6 months; and Timed Up and Go (TUG). Peripheral blood samples were collected for measurement of IL-6, CRP and D-dimer. Quantitative IL-6 and CRP levels were obtained using NOVEX® immunoassay (Invitrogen) and D-dimer levels were measured with Nanopia®D-dimer(Sekisui). Univariate analyses were performed to describe correlations of these three biomarkers and 6 measures of physical function. Results: 153 patients (mean age of 57.5 y, range 30-81 y) with stage I- III BC (Stages I [n=35; 23%], II [n=82; 54%], III [n=36; 24%]) were enrolled. Chemo regimens include: doxorubicin+cyclophosphamide/ paclitaxel(AC-T: 44%), docetaxel/cyclophosphamide (TC: 35%), docetaxel/carboplatin/trastuzumab (TCH: 7%) and other regimen(14%). Scores for the physical function measures are as follow: MOS (median 89, range 0-100); IADL (median 14, range 4-14); self-rated KPS (median 90, range 60-100); physician-rated KPS (median 100, range 80-100); TUG (median 9 seconds, range 5-18). Serum biomarkers measurements and distributions are listed in table 1. There were associations between decreased physical function by IADL and increased IL-6 (p&lt;0.01); decreased MOS and increased D-dimer (p&lt;0.01); increased number of falls and increased CRP (p=0.02) and D-dimer (p=0.04); increased TUG and increased IL-6 (p&lt;0.01), CRP (p&lt;0.01) and D-dimer (p=0.06) (Table 2). Physician and patient-rated KPS did not correlate with IL-6, CRP and D-dimer level. Conclusions: Baseline measures of inflammation and coagulation correlate with physical function measures among patients with breast cancer. Future analyses evaluating the association between aging biomarkers and measures of physical function with subsequent risk of chemotherapy toxicity is underway.

Table 1. Serum biomarkers measurement at baseline prior to initiation of chemotherapyBiomarkerMeanStandard DeviationMedianRangeIL-6 (pg/ml)4.35.13.00-48.0CRP(µg/ml)5.77.92.80.1-48.4D-dimer(µg/ml)0.70.60.60.1-3.3

Table 2. Univariate analysis of measures of physical functions versus biomarkersVariablesSpearman Coefficientp valueMOS vs D-dimer-0.21&lt;0.01IADL vs IL-6-0.27&lt;0.01No. of falls vs D-dimer0.160.04No. of falls vs CRP0.190.02TUG vs D-dimer0.150.06TUG vs IL-60.26&lt;0.01TUG vs CRP0.23&lt;0.01

Citation Format: Yuan Yuan, Nilesh Vora, Tao Feng, Joanne Mortimer, Thehang Luu, George Somlo, Joseph Chao, Vivi Tran, Shu Mi, Tim Synold, James Waisman, Laura Zavala, Vani Katheria, Arti Hurria. Association of baseline pro-inflammatory (IL-6, CRP) and coagulation (D-dimer) markers with baseline functional status in women with breast cancer (BC) undergoing chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-07.