Biological ageing and frailty markers in breast cancer patients

Abstract

Older cancer patients are a highly heterogeneous population in terms of global health and physiological reserves, and it is often difficult to determine the best treatment. Moreover, clinical tools currently used to assess global health require dedicated time and lack a standardized end score. Circulating markers of biological age and/or fitness could complement or partially substitute the existing screening tools. In this study we explored the relationship of potential ageing/frailty biomarkers with age and clinical frailty. On a population of 82 young and 162 older non-metastatic breast cancer patients, we measured mean leukocyte telomere length and plasma levels of interleukin-6 (IL-6), regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein 1 (MCP-1), insulin-like growth factor 1 (IGF-1). We also developed a new tool to summarize clinical frailty, designated Leuven Oncogeriatric Frailty Score (LOFS), by integrating GA results in a single, semi-continuous score. LOFS' median score was 8, on a scale from 0=frail to 10=fit. IL-6 levels were associated with chronological age in both groups and with clinical frailty in older breast cancer patients, whereas telomere length, IGF-1 and MCP-1 only correlated with age. Plasma IL-6 should be further explored as frailty biomarker in cancer patients.

The added value of geriatric screening and assessment for predicting overall survival in older patients with cancer

“…The LOFS is a GA summary score: it calculates a global GA end score that integrates 5 fundamental aspects determining a patient's fitness/frailty status (ie, his or her ability to autonomously perform activities of daily living [ADL and IADL], mental status [MMSE], nutritional status [MNA-SF], and comorbidities [CCI]) into a single semicontinuous score on a scale of 0 (severely frail) to 10 (fit) 41 (see Supporting Table 2). The LOFS is a GA summary score: it calculates a global GA end score that integrates 5 fundamental aspects determining a patient's fitness/frailty status (ie, his or her ability to autonomously perform activities of daily living [ADL and IADL], mental status [MMSE], nutritional status [MNA-SF], and comorbidities [CCI]) into a single semicontinuous score on a scale of 0 (severely frail) to 10 (fit) 41 (see Supporting Table 2).…”

How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms?

“…Another explanation could be the severity of inflammation. A study performed in breast cancer patients showed the IL-6 level significantly associated with frailty, but the CMV status was not reported (Brouwers et al 2015). In long-term care geriatric patients, higher baseline hs-CRP and IL-6 levels were associated with worse physical performance and gait speed at 12 months independent of age and comorbidity (Langmann et al 2017).…”

Impact of chemotherapy on medium-term physical function and activity of older breast cancer survivors, and associated biomarkers

“…Therefore, we evaluated the following biomarkers that have been associated with functional decline in the elderly: IL-6[28, 39, 55], D-dimers[56], albumin[57], IGF-1 & IGFBP3[58, 59], TNF-alpha[60] in plasma samples.…”

“…Chemotherapy treatment has potential to increase senescent cells leading to an increase in inflammatory and DNA damage burden[34], which could interfere with muscle function [35, 36]. Elevated pro-inflammatory cytokines are correlated with fatigue in breast cancer survivors[37], patients with cancer in general [38] and frailty in breast cancer survivors [39]. …”