Novel association of pre-chemotherapy immune cell profiles with functional decline and resilience in women with breast cancer receiving chemotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 549-549
Author(s):  
Nikesha Gilmore ◽  
Supriya Gupta Mohile ◽  
Huiwen Xu ◽  
Kah Poh Loh ◽  
Amber Kleckner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Physical Function ◽  
Immune Cell ◽  
Functional Decline ◽  
Cell Counts ◽  
Increased Risk ◽  
Novel Association ◽  
Pre Treatment ◽  
General Physical ◽  
Relationship Of

549 Background: Chemotherapy adversely affects physical function. While many patients recover after treatment (i.e. are resilient), some are unable to return to their pre-treatment function (i.e. are non-resilient). Since immune dysfunction may play a role in functional decline, we assessed the relationship of pre-chemotherapy immune cell profiles with functional decline and resilience in women with breast cancer receiving chemotherapy. Methods: This study was based on a large nationwide cohort study in women with stage I-III breast cancer. Physical function was measured by the Functional Assessment of Cancer Therapy: General – Physical subscale (FACT-PWB) ≤7 days before chemotherapy (T1), ≤1 month after chemotherapy (T2), and 6 months after T2 (T3). Functional decline at T2 and T3 was defined as > 1 point decrease (clinically meaningful difference) in FACT-PWD score from T1. Patients were considered non-resilient if they had T2 functional decline and did not return to within 1 point of their baseline FACT-PWB score by T3. Immune cell counts, neutrophil:lymphocyte ratio (NLR), and lymphocyte:monocyte ratio (LMR) were obtained at T1. Multivariate logistic regressions were used to determine whether immune cell counts and ratios were associated with functional decline and being non-resilient controlling for baseline FACT-PWD, age, race, education, and marital status. Results: One-third of patients (178/529; mean age 53, range 22-81) had functional decline from T1-T3. Of the 59% (n = 310) of patients with functional decline at T2, 50% (n = 147) did not recover by T3 (i.e. were non-resilient). Patients with a low ( < median) NLR at T1 were twice as likely to have functional decline by T3 than those with a high (≥ median) NLR [Adjusted Odds Ratio (AOR) 1.8, 95% CI: 1.2-2.8, p < 0.01]. Similarly, in patients with functional decline at T2, those with a low NLR at T1 were twice as likely to be non-resilient than those with high NLR (AOR: 1.9, 95% CI: 1.1-3.2, p = 0.01). Conversely, patients with high T1 lymphocytes were twice as likely to be non-resilient than those with low lymphocytes (AOR: 1.8, 95% CI: 1.1-3.1, p = 0.02). Conclusions: One-third of women with breast cancer have clinically meaningful, persistent functional decline six months after completing chemotherapy. Higher pre-chemotherapy lymphocytes and lower NLR may be useful to identify which women are at increased risk of functional decline and reduced ability to regain baseline physical function. These findings can inform interventions to ameliorate this decline.

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

2020 ◽  
Author(s):  
Nikesha Gilmore ◽  
Supriya Mohile ◽  
Lianlian Lei ◽  
Eva Culakova ◽  
Mostafa Mohamed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Immune Cell ◽  
Time Points ◽  
Markers Of Inflammation ◽  
Cell Counts ◽  
Increased Risk ◽  
Patients At Risk ◽  
Cellular Markers ◽  
Time Point

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<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<0.05), neutrophils (β=0.04; p<0.05), and NLR (β=0.04; p<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<0.05 and neutrophils: β=0.03; p<0.05, NLR: β=0.03; p<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

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

2020 ◽  
Author(s):  
Nikesha Gilmore ◽  
Supriya Mohile ◽  
Lianlian Lei ◽  
Eva Culakova ◽  
Mostafa Mohamed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
At Risk ◽  
Immune Cell ◽  
Time Points ◽  
Markers Of Inflammation ◽  
Cell Counts ◽  
Increased Risk ◽  
Patients At Risk ◽  
Cellular Markers ◽  
Time Point

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<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<0.05), neutrophils (β=0.04; p<0.05), and NLR (β=0.04; p<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<0.05, neutrophils: β=0.03; p<0.05, NLR: β=0.03; p<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

scholarly journals Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1685
Author(s):  
Antonino Grassadonia ◽  
Vincenzo Graziano ◽  
Laura Iezzi ◽  
Patrizia Vici ◽  
Maddalena Barba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Post Treatment ◽  
Neutrophil To Lymphocyte Ratio ◽  
Luminal Breast Cancer ◽  
Luminal A ◽  
Luminal B ◽  
Lymphocyte Ratio ◽  
Cell Counts ◽  
Pre Treatment

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

Evaluation of immunotherapy (I-O)-associated immune cell (IC) dynamics and PD-L1 expression using multispectral immunohistochemistry (mIHC) and single-cell hierarchical regression modeling in early-stage breast cancer (ESBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12070-e12070
Author(s):  
Katherine Sanchez ◽  
Maritza Martel ◽  
Shu-Ching Chang ◽  
Yaping Wu ◽  
Zhaoyu Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Nearest Neighbor ◽  
Immune Cell ◽  
Early Stage ◽  
Hierarchical Regression ◽  
Cytokine Therapy ◽  
Gm Csf ◽  
Multiple Regions ◽  
Pre Treatment

e12070 Background: In triple negative breast cancer (TNBC), anti-PD-L1 is associated with gains in overall survival, however only in tumors with > 1% PD-L1+ ICs. Locoregional cytokine therapy is being evaluated as a method of priming and redirecting ICs to tumors, which may increase I-O benefit particularly in PD-L1 negative tumors. We report a sensitive method of quantifying I-O-related changes in PD-L1 and ICs using mIHC and single-cell hierarchical regression, which controls for within-tumor and across-patient PD-L1/IC heterogeneity. Methods: Pre-treatment and resection tissues from a phase Ib trial of locoregional cytokines (IRX-2, n = 16 subjects) in ESBC were analyzed. IRX-2 contains immunostimulatory cytokines (GM-CSF, IL-2, IFN-α, INF-γ, and IL-12) and was injected in peri-areolar tissue, which communicates directly with tumor-draining lymphatics. Specimens were analyzed for 1) H&E stromal TILs score; 2) clinical PD-L1 IC expression (Ventana SP142, 2 blinded pathologists); and 3) mIHC (PerkinElmer Vectra). InForm software was used to obtain geospatial outputs of tumor cells (CK+) and ICs (CD3, CD8, CD163) across multiple regions of interest (mean:18; range: 9-32). Mixed-effects modeling was used to evaluate for changes in PD-L1, ICs, and IC/tumor distance metrics. Results: PD-L1 and IC quantity by mIHC was highly concordant with clinical PD-L1 IC classification (JT test = 211, p < .001) and TIL score (r = 0.77). Cytokine therapy was associated with higher PD-L1 IC classification in 9/13 tumors, and increased PD-L1 ICs by mIHC in 14/15 (+337%, 95% CI: 120,769%). After adjusting for heterogeneity, cytokine therapy increased CD3+CD8+ ICs (+173%, CI: 93,287%) and CD3+CD8- ICs (+120%, CI: 21,301%). Therapy was also associated with increased effector-helper T-cell clustering (nearest-neighbor distance, -40%, CI: -29,-50%) and effector cell tumor localization (stromal-tumor interface CD8+ density +90%, Cl: 74, 305%). Conclusions: Our method is concordant with clinical PD-L1 and sTILs scores, and can additionally quantify IC and IC distances. This assay may allow for comparative I-O assessments with increased resolution, and will be used in a randomized phase II trial of pembrolizumab, chemo +/- IRX-2 in stage II/III TNBC.

Benign Breast Diseases and Body Mass Index: Is There a Correlation?

2014 ◽  
Vol 80 (5) ◽  
pp. 461-465 ◽  
Author(s):  
Stacey O'Brien ◽  
Gopal Chandru Kowdley
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Body Mass ◽  
Breast Biopsy ◽  
Statistical Significance ◽  
Breast Disease ◽  
Breast Diseases ◽  
Increased Risk ◽  
Relationship Of ◽  
Risk Of Cancer

Breast cancer is the leading cancer affecting women in America. Body mass index (BMI) is a known risk factor for the development of breast cancer. The relationship of BMI to benign breast disease is less clear. In addition, certain benign pathologies are associated with an increased risk of cancer. We sought to measure the incidence of benign pathologies and to correlate these findings with BMI and age. All patients undergoing breast biopsy at our center from 2000 to 2005 were identified (n = 1717). Age, BMI, family history, sex, and diagnosis were determined. Patients were grouped into BMI, age, and intervention groups. χ2 ( P < 0.05) was used to identify statistical significance. Fibrocystic disease and fibroadenoma were seen with a lower incidence for patients older than 55 years of age, whereas pathologies requiring further surgical intervention were seen in higher proportions in patients older than 55 years of age. All pathologies were noted to decrease with increasing BMI, except for fibroadenoma, which peaked in BMI group 25 to 29.9 kg/m2. The presence of benign pathologies was associated with age as expected. Interestingly, although BMI is associated with increased risk of breast cancer, increasing BMI was not associated with benign pathologies that are associated with increased risk of breast cancer. Further study of this area is warranted.

scholarly journals Rare coding variants in five DNA damage repair genes associate with timing of natural menopause

2021 ◽  
Author(s):  
Lucas D Ward ◽  
Margaret M Parker ◽  
Aimee M Deaton ◽  
Ho-Chou Tu ◽  
Alexander O Flynn-Carroll ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Disease Risk ◽  
Polycystic Ovary ◽  
Dna Damage Repair ◽  
Cancer Genes ◽  
Natural Menopause ◽  
Cell Counts ◽  
Damage Repair ◽  
Increased Risk

The age of menopause is associated with fertility and disease risk, and its genetic control is of great interest. We used whole-exome sequences from 119,992 women in the UK Biobank to test for associations between rare damaging variants and age at natural menopause. Rare damaging variants in three genes significantly associated with menopause: CHEK2 (p = 6.2 × 10-51) and DCLRE1A (p = 1.2 × 10-12) with later menopause and TOP3A (p = 8.8 × 10-8) with earlier menopause. Two additional genes were suggestive: RAD54L (p = 2.3 × 10-6) with later menopause and HROB (p = 2.7 × 10-6) with earlier menopause. In a follow-up analysis of repeated questionnaires in women who were initially pre-menopausal, CHEK2, TOP3A, and RAD54L genotype associated with subsequent menopause. Consistent with previous GWAS, all five genes are involved in the DNA-damage repair pathway. Phenome-wide scans across 363,977 men and women revealed that in addition to known associations with cancers and blood cell counts, rare variants in CHEK2 also associated with increased risk of uterine fibroids, polycystic ovary syndrome, and prostate hypertrophy; these associations are not shared with higher-penetrance breast cancer genes. Causal mediation analysis suggests that approximately 8% of the breast cancer risk conferred by CHEK2 pathogenic variants after menopause is mediated through delayed menopause.

scholarly journals Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

2019 ◽  
Author(s):  
Chang Ik Yoon ◽  
So Eun Park ◽  
Yoon Jin Cha ◽  
Soong June Bae ◽  
Chi Hwan Cha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Blood Cell ◽  
Peripheral Blood ◽  
Immune Cell ◽  
Laboratory Data ◽  
Peripheral Blood Cell ◽  
Cell Mediated Immunity ◽  
Breast Cancer Patients ◽  
Cell Counts ◽  
Blood Cell Counts

AbstractTumor-infiltrating lymphocytes (TILs) might be associated with host-cell mediated immunity, which could be partly reflected by peripheral blood cell counts. We aimed to investigate whether peripheral blood cell counts are associated with TILs in breast cancer. Between August 2016 and July 2018, we evaluated the percentage of stromal TILs in breast cancer patients who underwent primary surgery, using the standardized methodology proposed by the international TIL Working Group. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors having high TIL levels (≥ 50%). Peripheral blood cell counts including absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC) and neutrophil-to-lymphocyte ratio (NLR) was obtained from pretreatment laboratory data. Of the 684 patients, 99 (17.2%) had LPBC, and 478 (82.8%) had non-LBPC. In a comparison of 3 markers of peripheral blood counts, LPBC had a significantly lower mean ANC than non-LPBC (3,330 vs. 3,660; P=0.004), but the other means were not different. Decreasing ANC was an independent clinical factor in predicting LPBC (OR: 0.736, 95% CI: 0.591-0.917; P=0.004). Low peripheral ANC might be linked with LPBC, supporting the hypothesis that systemic immune cell counts might be associated with the tumor-immune microenvironment.

Mammographic density as marker of increased risk of breast cancer

2021 ◽  
pp. 41-48
Author(s):  
P. G. Labazanova ◽  
M. V. Budanova ◽  
I. I. Burdina ◽  
S. B. Zapirova ◽  
M. L. Mazo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammographic Density ◽  
Molecular Genetic ◽  
Breast Cancer Risk Factor ◽  
Develop Breast Cancer ◽  
Reproductive Age ◽  
Genetic Studies ◽  
Increased Risk ◽  
Relationship Of ◽  
The Relationship

‘Mammographic density’ (MD) is a concept that has entered medical practice since 2017. as a marker of breast cancer risk factor (BC) according to the international classifiation of NCCN. The term reflcts the degree of severity of benign diffuse breast dysplasia in women of post-reproductive age. MD is determined by the ratio of stromal, epithelial, and adipose tissue. According to the literature, in young women, high MD limits the possibilities of X-ray mammography, reducing its effectiveness in oncomammoscreening, leading to the detection of advanced forms of breast cancer. Post-reproductive women with high MD are more likely to develop breast cancer than those with low MD. In this regard, MD is of particular interest for studying its role in oncogenesis. Recent molecular genetic studies of the differences between high and low MD explain the main biological reasons why post-reproductive women with dense breast structure are at a higher risk of developing breast cancer. The aim is to identify the factors that inflence the relationship of MD with the risk of developing breast cancer based on a comparative analysis of molecular genetic studies and radiological manifestations of MD of different severity and to identify the factors that contribute to the formation of MD variants.

Exercise Immunology: Nutritional Countermeasures

2001 ◽  
Vol 26 (S1) ◽  
pp. S45-S55 ◽  
Author(s):  
David C. Nieman
Keyword(s):  
Immune Cell ◽  
Moderate Physical Activity ◽  
Upper Respiratory Tract ◽  
Carbohydrate Supplementation ◽  
Exercise Immunology ◽  
Cell Counts ◽  
Increased Risk ◽  
Oxidative Burst Activity ◽  
Inflammatory Cytokine Response ◽  
Upper Respiratory

In contrast to moderate physical activity, prolonged and intensive exertion causes numerous changes in immunity that reflect physiologic stress and suppression, and an increased risk of upper respiratory tract infection. Enzymes in immune cells require the presence of micronutrients, leading to attempts by investigators to alter changes in immunity following heavy exertion through use of nutritional supplements, primarily zinc, dietary fat, vitamin C and other antioxidants, glutamine, and carbohydrate. Except for carbohydrate supplementation, none of these nutrients has emerged as an effective countermeasure to exerciseinduced immunosuppression. Data from several studies of endurance athletes suggest that carbohydrate compared to placebo ingestion is associated with an attenuated cortisol, growth hormone, and epinephrine response to heavy exertion, fewer perturbations in blood immune cell counts, lower granulocyte and monocyte phagocytosis and oxidative burst activity, and a diminished pro- and anti-inflammatory cytokine response. Overall, the hormonal and immune responses to carbohydrate compared to placebo ingestion during intensive exercise suggest that physiologic stress and inflammation are diminished, although clinical significance awaits further research.

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