The Longitudinal Relationship Between Immune Cell Profiles and Frailty in Patients with Breast Cancer receiving Chemotherapy

Abstract Background: Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood.Methods: This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n=581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1; ≤7 days before first cycle), post-chemotherapy (T2; ≤ 1 month after last cycle), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time-points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time-points. Separate linear regressions were used to evaluate the associations of: 1) cell counts at T1 with frailty at T1, T2, and T3 and 2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time-point. Results: From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p&lt;0.01) and returned to T1 levels by the T3 time-point (1.3 vs 1.3; p=0.85). At the T1 time-point, there was a positive association between cellular markers of inflammation and frailty: WBC (β=0.04; p&lt;0.05), neutrophils (β=0.04; p&lt;0.05), and NLR (β=0.04; p&lt;0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β=0.02; p&lt;0.05, neutrophils: β=0.03; p&lt;0.05, NLR: β=0.03; p&lt;0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy. Conclusions: In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01382082</jats:p

The longitudinal relationship between immune cell profiles and frailty in patients with breast cancer receiving chemotherapy

Abstract Background Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood. Methods This study was a secondary analysis of a large nationwide cohort study of women with stage I–IIIC breast cancer (n = 581, mean age 53.4; range 22–81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0–4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time points. Separate linear regressions were used to evaluate the associations of (1) cell counts at T1 with frailty at T1, T2, and T3 and (2) change in cell counts (T2–T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time point. Results From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p &lt; 0.01) and returned to T1 levels by the T3 time point (1.3 vs 1.3; p = 0.85). At the T1 time point, there was a positive association between cellular markers of inflammation and frailty: WBC (β = 0.04; p &lt; 0.05), neutrophils (β = 0.04; p &lt; 0.05), and NLR (β = 0.04; p &lt; 0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β = 0.02, p &lt; 0.05; neutrophils: β = 0.03, p &lt; 0.05; NLR: β = 0.03; p &lt; 0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy. Conclusions In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy. Trial registration ClinicalTrials.gov, NCT01382082 </jats:sec

The longitudinal relationship between immune cell profiles and frailty in patients with breast cancer receiving chemotherapy.

BACKGROUND: Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood. METHODS: This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n = 581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time points. Separate linear regressions were used to evaluate the associations of (1) cell counts at T1 with frailty at T1, T2, and T3 and (2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time point. RESULTS: From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p \u3c 0.01) and returned to T1 levels by the T3 time point (1.3 vs 1.3; p = 0.85). At the T1 time point, there was a positive association between cellular markers of inflammation and frailty: WBC (β = 0.04; p \u3c 0.05), neutrophils (β = 0.04; p \u3c 0.05), and NLR (β = 0.04; p \u3c 0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β = 0.02, p \u3c 0.05; neutrophils: β = 0.03, p \u3c 0.05; NLR: β = 0.03; p \u3c 0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy. CONCLUSIONS: In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01382082

Physical Activity Patterns and Relationships With Cognitive Function in Patients With Breast Cancer Before, During, and After Chemotherapy in a Prospective, Nationwide Study.

PURPOSE: Physical activity (PA) is a promising intervention for cancer-related cognitive decline, yet research assessing its use during chemotherapy is limited. This study evaluated patterns of PA before, during, and after chemotherapy in patients with breast cancer and the association between PA and cognitive function. METHODS: In a nationwide, prospective cohort study, we assessed PA (Aerobics Center Longitudinal Study PA measure) and perceived and objectively measured cognitive functioning (Functional Assessment of Cancer Therapy-Cognitive, Delayed Match to Sample, and Rapid Visual Processing measures) at prechemotherapy (T1), postchemotherapy (T2), and 6 months postchemotherapy (T3) in patients with breast cancer and cancer-free, age-matched controls at equivalent time points. Longitudinal linear mixed-effects models (LMMs) characterized PA changes over time between patients and controls, adjusting for demographic and clinical factors. LMMs further estimated the role of prechemotherapy PA and changes in PA during chemotherapy on cognitive changes over time. RESULTS: Patients with stage I-IIIC breast cancer (n = 580; age M [standard deviation] = 53.4 [10.6] years) and controls (n = 363; age M [standard deviation] = 52.6 [10.3] years) were included. One third of patients met national PA guidelines at T1, dropping to 21% at T2 before rising to 37% at T3. LMMs revealed declines in PA from T1 to T2 in patients compared with controls (all CONCLUSION: This nationwide study demonstrates that PA maintenance before and during chemotherapy is associated with better cognitive function immediately and 6 months after chemotherapy completion

The Longitudinal Relationship between Immune Cell Profiles and Frailty in Patients with Breast Cancer receiving Chemotherapy

Abstract Background: Frailty is associated with an increased risk of chemotherapy toxicity. Cellular markers of inflammation can help identify patients with frailty characteristics. However, the role of cellular markers of inflammation in identifying patients at risk of developing chemotherapy-induced frailty and their clinical utility are not fully understood.Methods: This study was a secondary analysis of a large nationwide cohort study of women with stage I-IIIC breast cancer (n=581, mean age 53.4; range 22-81). Measures were completed pre-chemotherapy (T1), post-chemotherapy (T2), and 6 months post-chemotherapy (T3). Frailty was assessed at all three time-points using a modified Fried score consisting of four self-reported measures (weakness, exhaustion, physical activity, and walking speed; 0-4, 1 point for each). Immune cell counts as well as neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) were obtained at T1 and T2 time-points. Separate linear regressions were used to evaluate the associations of: 1) cell counts at T1 with frailty at T1, T2, and T3 and 2) change in cell counts (T2-T1) with frailty at T2 and T3. We controlled for relevant covariates and frailty at the T1 time-point.Results: From T1 to T2, the mean frailty score increased (1.3 vs 2.0; p&lt;0.01) and returned to T1 levels by the T3 time-point (1.3 vs 1.3; p=0.85). At the T1 time-point, there was a positive association between cellular markers of inflammation and frailty: WBC (β=0.04; p&lt;0.05), neutrophils (β=0.04; p&lt;0.05), and NLR (β=0.04; p&lt;0.01). From T1 to T2, a greater increase in cellular markers of inflammation was associated with frailty at T2 (WBC: β=0.02; p&lt;0.05 and neutrophils: β=0.03; p&lt;0.05, NLR: β=0.03; p&lt;0.01). These associations remained significant after controlling for the receipt of growth factors with chemotherapy and the time between when laboratory data was provided and the start or end of chemotherapy.Conclusions: In patients with breast cancer undergoing chemotherapy, cellular markers of inflammation are associated with frailty. Immune cell counts may help clinicians identify patients at risk of frailty during chemotherapy.Trial Registration: ClinicalTrials.gov Identifier: NCT01382082</jats:p

Patterns in circulating microRNA in black (B) versus white (W) patients with triple-negative (TN) breast cancer (BC).

1046 Background: Breast cancer is by far more common in W than in B women. Black women have more aggressive disease that occurs almost a decade earlier, it is usually triple negative and has a lower survival. Objectives to determine 1) if plasma miRNA expression differs between B and W women, and 2) if variation in miRs may explain the observed survival difference in TNBC in W compared to B women. Methods: We determined miRNA profiles in plasma collected before removal of breast tumors in three groups of W and B women: 1) normal controls (N), 2) TN and 2) ER/PR positive BC. Expression miRNA profiling of 754 miRNAs on the ABI Open Array detected 101miRNAs in plasma. We compared miRNA expression in cancer patients and race-matched controls. A moderated t-statistic through the R/Bioconductor 'limma' was used to compare the mean response between subject factors of interest. Results with a p&lt;0.05 were considered statistically significant. Characteristics: 32 patients were included in this analysis (mean age 50 years; range 31-68), 10 had stage III TNBC (5 B &amp; 5 W); 10 had stage III ER/PR+BC (5 B, 5 W); and 12 were controls (6 B, 6 W) Results: W TNBC patients overexpressed (15 fold higher than normal) 20 miRs in plasma (let-7d, let7g, miR-103, -10a, 15a, -9, -99b, -181a, -18a, -502, -187, -365 and others), these miRs were not found in any of the B patients. Six microRNAs (such as miR-34a, -127 and others) were 15 fold higher than normal controls in B cancer patients, these miRs were not detected in W patients with TNBC. Four miRs in B and 8 miRs in W were not previously reported in association with breast cancer suggesting that they may be connected to the host response. Conclusions: The striking difference in the patterns of plasma miRNA expression between B and W patients may provide the key to the large difference in outcome between these groups when receiving similar treatments, the worse prognosis group may carry the miRs that promote metastasis. The seed-soil hypothesis may explain the better prognosis in W patients. W women may carry those miRNAs that support an “exaggerated” response to systemic treatment, while the B may have the miRs that favour metastasis. </jats:p