Abstract PS8-03: Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer
Authors: Sedrak Mina S , Sun Canlan , Muss Hyman , Freedman Rachel A. , Magnuson Allison , Gross Cary P. , Tew William P. , Klepin Heidi D. , Wildes Tanya M. , Dotan Efrat , O'Connor Tracey , Fenton Mary Ann , Sharma Ruby , Chapman Andrew , Owusu Cynthia , Chow Selina , Kim Heeyoung , Katheria Vani , LaBarge Mark , Dale William , Armenian Saro , Neuhausen Susan , Cohen Harvey J. 
Published: February 2021

Abstract
Background: Physical resilience, the ability to resist decline and maintain functional status despite a stressor such as chemotherapy, is a central aspect of successful aging. Understanding clinical and biological factors associated with resilience in older women receiving chemotherapy for early breast cancer may facilitate the development of targeted interventions to maintain an individual’s robustness.Methods: Women age ≥65 (N=406) with Stage I-III breast cancer who were part of a clinical study of neo/adjuvant chemotherapy in older women were recruited from 16 sites (NCT01472094, R01AG037037). The Deficit Accumulation Index (DAI), a continuous score (0-1) calculated based on 51-items from geriatric assessment data (Cohen et al Cancer 2017), was measured before and after receipt of chemotherapy. DAI was categorized as robust (0.0&lt;0.2), prefrail (0.2&lt;0.35) and frail (≥0.35). Baseline blood biomarkers of inflammation (interleukin-6 [IL-6], C-reactive protein [CRP]) and coagulation (D-dimer) were measured and defined as elevated if values were ≥median values in this cohort. The population of interest was older women who were robust prior to initiation of chemotherapy. The primary outcome was resilience (Yes/No); yes, defined as retaining robustness [DAI 0.0&lt;0.2] before and ≤1 month after chemotherapy. Demographic, disease, and pretreatment variables associated with resilience in univariate analysis with p&lt;0.1 were further adjusted using multivariable logistic regression to examine the associations between baseline biomarkers and resilience. Results: Before starting chemotherapy, 324 of 406 (80%) older women were robust. The median age was 70 (range 65-86), 61% had stage II or III disease, 29% had HER2+ disease, 22% had TNBC, 37% received an anthracycline-based regimen, 49% had planned duration of treatment &gt; 12 weeks, and 74% received primary prophylaxis with WBC growth factors. Among these 324 robust older women, 253 (78%) remained robust (resilient) at the end of chemotherapy, 63 (19%) became prefrail, and 8 (3%) became frail. In univariate analyses, patients treated with anthracycline (OR=0.63, p=0.09), planned duration of treatment &gt; 12 weeks (OR=0.56, p=0.04), elevated IL-6 ≥2.7 pg/ml (OR=0.59, p=0.05), elevated CRP ≥4.3 μg/ml (OR=0.57, p=0.04), elevated D-dimer ≥0.7 μg/ml (OR=0.61, p=0.07), or at least one elevated biomarker (OR=0.18, p&lt;0.001) at baseline were less likely to be resilient after systemic chemotherapy. Adjusting for anthracyclines and treatment duration, patients who had one or more elevated biomarker were still significantly less likely to be resilient (OR=0.15, 95 CI 0.04-0.49, p=0.002) compared to those with no elevated biomarkers at baseline.
Conclusions: In this cohort of older women with early breast cancer who were robust prior to initiation of chemotherapy, 22% became prefrail or frail at end of treatment. Resilience to chemotherapy was related to inflammatory and coagulation biomarkers. Further research is needed to examine the mechanism underlying why some older women are resilient and retain their robustness after receiving treatment, whereas others experience decline, and further explore the role of inflammation/coagulation in this phenomenon.
Table 1. Multivariable associations between baseline blood biomarkers and resilienceResilient (n=253) No. %Non-resilient (n=71) No. %Multivariable OR (95%CI)P value# of elevated biomarkers*064 (25)4 (6)1.00190 (36)29 (41)0.16 (0.05-0.55)0.004255 (22)22 (31)0.14 (0.04-0.49)0.002344 (17)16 (23)0.14 (0.04-0.51)0.003No elevated biomarker64 (25)4 (6)1.00At least one elevated189 (75)67 (94)0.15 (0.04-0.49)0.002*Biomarkers were defined as elevated using the entire cohort median value as cut off points (IL-6 ≥2.7 pg/ml, CRP ≥4.3 μg/ml, and D-dimer ≥0.7 μg/ml). Combined effects of biomarkers were examined by creating a four-level categorical combination variable: 0=all three biomarkers are &lt;median; 1=one of the biomarkers ≥median; 2=two of the biomarkers ≥median; and, 3=all three biomarkers ≥median. A dichotomized variable was also created comparing none (all three biomarkers are &lt;median) vs at least one biomarker elevated (≥median).
Citation Format: Mina S Sedrak, Canlan Sun, Hyman Muss, Rachel A. Freedman, Allison Magnuson, Cary P. Gross, William P. Tew, Heidi D. Klepin, Tanya M. Wildes, Efrat Dotan, Tracey O'Connor, Mary Ann Fenton, Ruby Sharma, Andrew Chapman, Cynthia Owusu, Selina Chow, Heeyoung Kim, Vani Katheria, Mark LaBarge, William Dale, Saro Armenian, Susan Neuhausen, Harvey J. Cohen. Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-03.