Abstract P6-07-13: Association of pre-chemotherapy peripheral blood pro-inflammatory (IL-6, CRP) and coagulation (D-dimer) markers with chemotherapy toxicity in women with breast cancer
Authors: Yuan Y , Vora N , Sun C , Li D , Mortimer J , Luu T-h , Somlo G , Waisman J , Chao J , Katheria V , Synold T , Tran V , Mi S , Levi A , Yost S , Arsenyan A , Choi J , Zavala L , Hurria A 
Published: May 2019

Background: Pro-inflammatory and coagulation factors serve as biomarkers of aging and functional reserve. Chemotherapy (chemo) decreases the risk of relapse and mortality from breast cancer (BC); however, it comes with the risk of toxicity. The utility of these markers as biological risk factors for chemotherapy toxicity in patients with BC is unknown. This study was performed to determine if pre-chemo IL-6, CRP and D-dimer were associated with chemotherapy toxicity in women with breast cancer receiving adjuvant or neoadjuvant chemo.

Methods: This study enrolled women across the aging spectrum with Stage I-III BC. Prior to (neo)adjuvant chemo initiation, peripheral blood was collected for IL-6, CRP, and D-dimer. (Neo)adjuvant chemo regimens were prescribed at the MD's discretion. Grade 3 or above toxicities defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, were captured. Univariate and multivariate analyses were performed to describe the association of these biomarkers with chemo toxicity controlling for relevant tumor and host factors (stage, receptor status, age and co-morbidities).

Results: 159 patients (mean age of 58.4, range 30-81) with stage I-III BC (Stage I [n=34; 21.3%], Stage II [n=88; 55.3%], and Stage III [n=37; 23.3%]) were enrolled. 89% and 11% received adjuvant and neoadjuvant chemotherapy respectively. Chemo regimens include: doxorubicin+cyclophosphamide/paclitaxel (37%), docetaxel/cyclophosphamide (35%), doxorubicin+cyclophosphamide/paclitaxel/trastuzumab (7%), docetaxel/carboplatin/trastuzumab (7%), sequential doxorubicin/paclitaxel/cyclophosphamide (5) and other regimens (9%). At least one grade 3 to 5 toxicity occurred in 70 (44%) patients (93% grade 3, 6% grade 4, and 1% grade 5). Grade 3 to 5 hematological (heme) and non-heme toxicity occurred in 23% and 39%, respectively. The most common grade 3 to 4 heme toxicities were anemia (38%), leucopenia (29%), and neutropenia (24%). One patient developed grade 5 toxicity (pneumonitis). The most common grade 3-4 non-heme toxicities were electrolyte abnormalities (12%), neuropathy (10%), mucositis (8%), infection (8%) and fatigue (8%). Univariate analysis revealed an association of increased pre-chemo D-dimer and grade ≥3 toxicity (p=0.02) (Table 1). Among the clinical factors, increased age and number of co-morbidities was associated with grade ≥3 toxicities (p&lt;0.01 respectively). After controlling for age and number of comorbidities the association between elevated D-dimer and chemo toxicities remain significant (OR 2.1 [95%CI1.1-3.9]).

Conclusions: Grade 3-5 toxicities are common in women with breast cancer undergoing (neo)adjuvant chemo. A biomarker of aging, D-dimer, is associated with increased risk of chemo toxicity.

Table 1 Association of peripheral blood biomarkers of aging and Grade 3-5 chemo toxicities Grade ≥3 Toxicity (N=89)Grade &lt; 3 Toxicity (N=70)P-ValueIL-6 (pg/ml) Median (Range)1.7(0 -42.1)1.9 (0-19.6)0.57D-dimer (µg/ml) Median (Range)0.8(0.1-3.3)0.5 (0.1-2.6)0.02CRP (µg/ml) Median (Range)2.6(0.1-48.4)3.0 (0.2-44.3)0.57

Citation Format: Yuan Y, Vora N, Sun C, Li D, Mortimer J, Luu T-h, Somlo G, Waisman J, Chao J, Katheria V, Synold T, Tran V, Mi S, Levi A, Yost S, Arsenyan A, Choi J, Zavala L, Hurria A. Association of pre-chemotherapy peripheral blood pro-inflammatory (IL-6, CRP) and coagulation (D-dimer) markers with chemotherapy toxicity in women with breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-13.