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  • br In this study we sought to determine whether


    In this study, we sought to determine whether pre-chemotherapy levels of inflammatory cytokines and receptors are predictive of post-chemotherapy frailty in patients 50 years and older with breast cancer receiving adjuvant or neoadjuvant chemotherapy. We hypothesized that patients with breast cancer are more frail that non-cancer individ-uals prior to initiating chemotherapy, and this frailty is intensified after chemotherapy treatment. We also hypothesized that patients with breast cancer who are in a heightened inflammatory state prior to receiving chemotherapy will develop chemotherapy-associated frailty.
    2. Methods
    This is a secondary analysis to investigate the association of pre-chemotherapy inflammatory cytokines and receptors with post-chemotherapy frailty in female patients over the age of 50 with breast cancer undergoing curative intent treatment. The primary study was a prospective cohort longitudinal trial designed to assess the longitudinal effects of chemotherapy on cognition [25,26]. Patients with breast can-cer and age-matched non-cancer controls were recruited nationwide through the University of Rochester Cancer Center (URCC) National Cancer Institute (NCI) Community Oncology Research Program (NCORP) Research Base and affiliate NCORPs. Measures (surveys and blood draws) for patients with breast cancer were completed within 7 days prior to the first beta-Nicotinamide mononucleotide of chemotherapy (pre-chemotherapy) and within 4 weeks after chemotherapy completion (post-chemother-apy). Measures were completed at the same time-points for non-cancer controls. For this pilot study, we included patients with breast cancer and their age-matched non-cancer controls who were
    ≥ 50 years and had serum cytokine analysis of IL-6, and TNFRI and TNFRII available (Fig. 1). Institutional review boards at the URCC NCORP Research Base and each of the NCORP Community Affiliates approved the study. All subjects provided informed consent before completing study requirements.
    2.2. Study Participants
    We included patients with a diagnosis of invasive breast cancer (stage I-IIIC) who were scheduled to begin a course of adjuvant or neo-adjuvant chemotherapy. Based on the original study, other inclusion criteria for both patients and non-cancer controls were: 1) chemother-apy naïve, 2) life expectancy N10 months, 3) able to speak and read En-glish, and 4) able to provide written informed consent. Patients were excluded if they were: 1) hospitalized at the time of study or had been hospitalized within the last year for a psychiatric illness, 2) diagnosed with a neurodegenerative disease, 3) had any primary central nervous system disease, 4) scheduled to receive concurrent radiation treatment while receiving chemotherapy, 5) have (or have had) metastatic dis-ease, pregnant and/or, 6) colorblind. Non-cancer controls were within 5 years of age with the matched patient with breast cancer [26].
    All measures were collected by clinical research associates at the community affiliated sites.
    Demographics: Participants self-reported age, race, education and marital status.
    Health Status Measures: Measures occurred at pre- and post-chemotherapy time-points. Performance status was assessed using Karnofsky Performance Score (KPS) [27]. Pain, distress, general physical activity, and exercise were assessed using the Symptom Inventory (SI),
    a validated multi-symptom patient-reported outcome measure that evaluates the severity (0–10; not at all to as bad as you can imagine) and degree of interference (0–10; did not interfere to interfered completely) of cancer-related symptoms [28]. Symptoms were chosen from the SI based on symptoms that were closely related to components of frailty and could also describe the health status of patients with can-cer. The Pittsburgh Sleep Quality Index, a self-reported measure of sleep habits, was used to evaluate sleep quality (very good to very bad) and feelings of anhedonia (no problem at all to a very big problem) [29].
    Frailty Components: Frailty was measured using Fried's frailty pheno-type, a previously described and validated measure of frailty in the gen-eral geriatric population, which includes self-reported exhaustion, weakness, slow walking speed, low physical activity, and unintentional weight loss [1]. Frailty was assessed at pre- and post-chemotherapy time-points. As the parent study did not include measures to evaluate unintentional weight loss at the pre-chemotherapy time-point, we used a modified Fried's score based on the four available components (weakness, slow walking, low physical activity, and exhaustion). These components were measured using self-reported weakness (≥ 4 on scale of 1–10 on SI), exhaustion (≥ 4 on scale of 1–10 on SI), walking speed (b2 mph on Aerobic Center Longitudinal Study Physical Activity Questionnaire (ACLS)), and physical activity (b150 min/week on ACLS [30,31]). For each component, subjects received a score of one if they met the cut-off for that component and zero if they did not. The scores were summed and participants' total scores ranged from 0 to 4 to repre-