Inflammation In Breast Cancer Survivors Research Articles

Effect of minocycline on changes in affective behaviors, cognitive function, and inflammation in breast cancer survivors undergoing chemotherapy: a pilot randomized controlled trial.

Minocycline suppresses chemotherapy-induced neuroinflammation in preclinical models, but its effects in cancer survivors are unknown. This study evaluated the longitudinal effects of minocycline on affective behaviors, cognitive functions, and inflammation in women with breast cancer (BC) undergoing chemotherapy. This is a pilot, double-blind, randomized controlled trial of oral minocycline (100mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated. Fifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6M (p = 0.01). Despite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation.

Adherence to a MIND Diet Pattern Is Associated With Better Cognitive Function and Less Peripheral Inflammation in Breast Cancer Survivors

Adherence to a MIND Diet Pattern Is Associated With Better Cognitive Function and Less Peripheral Inflammation in Breast Cancer Survivors

Tai Chi compared with cognitive behavioral therapy and the reversal of systemic, cellular and genomic markers of inflammation in breast cancer survivors with insomnia: A randomized clinical trial

BackgroundInsomnia contributes to inflammation in breast cancer survivors. This study evaluates whether insomnia treatment reverses inflammation in breast cancer survivors with insomnia. MethodsParticipants (n = 90) were randomized to 3 months of Tai Chi (n = 45) or cognitive behavioral therapy for insomnia (CBT-I)(n = 45), and followed for one year post-intervention to 15 month endpoint. Our previous report found that Tai Chi as compared to CBT-I resulted in similar rates of insomnia response and remission over 15 months. Here, we analyze changes in plasma C-reactive protein and pro- and anti-inflammatory cytokines, Toll-like receptor (TLR)-4 stimulated monocyte production of interleukin (IL)-6 and tumor necrosis factor-α (TNF), and cellular pro-inflammatory and anti-viral gene expression (Conserved Transcriptional Response to Adversity RNA profile; CTRA) over 15 months. ResultsInsomnia treatment resulted in decreases in the TLR-4 stimulated monocyte production of IL-6, TNF, and their co-expression, as well as decreases in the CTRA profile, decreases inflammatory gene transcripts, and increases in anti-viral gene transcripts over 15 months (all P’s < 0.01). In addition, as compared to CBT-I, Tai Chi resulted in greater decreases in plasma IL-6 (P < 0.05), and greater decreases in TLR-4 activated monocyte production of IL-6 and co-expression of IL-6 and TNF at 15 month endpoint. CBT-I resulted in greater increases in anti-viral gene transcripts. ConclusionsAdministration of either CBT-I or Tai Chi effectively treats insomnia, and shows additional benefits of reducing cellular and genomic markers of inflammation, and increasing anti-viral genomic markers in breast cancer survivors with insomnia. Tai Chi, as compared to CBT-I, yields greater and more durable decreases in systemic- and cellular inflammation. Targeting insomnia might mitigate the risk of inflammation-related co-morbidities in breast cancer survivors.

Adherence to the American Cancer Society guidelines on nutrition and physical activity for cancer survivors and biomarkers of inflammation among breast cancer survivors.

This study investigated whether adherence to the overall lifestyle recommendations in the American Cancer Society (ACS) guidelines on nutrition and physical activity for cancer survivors was associated with inflammation in breast cancer survivors. The study included 409 women who had undergone breast cancer surgery at least 1 year before enrollment. A generalized linear model was used to estimate the least square means and 95% confidence intervals of plasma levels of inflammatory markers according to lifestyle factors defined in terms of adherence to the ACS guidelines. Higher overall adherence scores were associated with lower levels of high-sensitivity C-reactive protein (hs-CRP) (p for trend=0.015) and higher levels of adiponectin (p for trend=0.009). Similar significant associations of hs-CRP (p for trend= 0.004) and adiponectin (p for trend=0.010) levels were observed with the score for the body mass index (BMI) component of the adherence score. A higher diet component score was associated with a higher adiponectin level (p for trend=0.020), but there was no significant association for the physical activity component score. The present study's findings suggest that maintaining a healthy lifestyle according to the ACS guidelines was associated with beneficial effects on inflammatory marker levels, especially hs-CRP and adiponectin, among breast cancer survivors. Among the 3 components of lifestyle guidelines, the BMI component exhibited the most similar tendency to the overall adherence score in relation to inflammatory indicators. Further prospective and intervention studies are needed to investigate longitudinal associations between lifestyle factors and inflammatory markers among breast cancer survivors.

The Impact of Mindfulness on Functional Brain Connectivity and Peripheral Inflammation in Breast Cancer Survivors with Cognitive Complaints.

Cancer-related cognitive impairment (CRCI) has been linked to functional brain changes and inflammatory processes. Hence, interventions targeting these underlying mechanisms are needed. In this study, we investigated the effects of a mindfulness-based intervention on brain function and inflammatory profiles in breast cancer survivors with CRCI. Female breast cancer survivors reporting cognitive complaints (n = 117) were randomly assigned to a mindfulness-based intervention (n = 43), physical training (n = 36), or waitlist control condition (n = 38). Region-of-interest (ROI) and graph theory analyses of resting state functional MRI data were performed to study longitudinal group differences in functional connectivity and organization in the default mode, dorsal attention, salience, and frontoparietal network. Additionally, bead-based immunoassays were used to investigate the differences in inflammatory profiles on serum samples. Measures were collected before, immediately after and three months post-intervention. No ROI-to-ROI functional connectivity changes were identified. Compared to no intervention, graph analysis showed a larger decrease in clustering coefficient after mindfulness and physical training. Additionally, a larger increase in global efficiency after physical training was identified. Furthermore, the physical training group showed a larger decrease in an inflammatory profile compared to no intervention (IL-12p70, IFN-γ, IL-1β, and IL-8). Both mindfulness and physical training induced changes in the functional organization of networks related to attention, emotion processing, and executive functioning. While both interventions reduced functional segregation, only physical training increased functional integration of the neural network. In conclusion, physical training had the most pronounced effects on functional network organization and biomarkers of inflammation, two mechanisms that might be involved in CRCI.

Psychological measures of stress and biomarkers of inflammation, aging, and endothelial dysfunction in breast cancer survivors on aromatase inhibitors

The use of aromatase inhibitors (AIs) is associated with higher rates of cardiovascular events and lower endothelial function in breast cancer survivors. Psychosocial stress is associated with higher levels of inflammatory and aging markers, and lower endothelial function in otherwise healthy subjects. These associations among breast cancer survivors on AIs are not well defined. A cross-sectional study of 30 breast cancer survivors on AIs was performed to assess the associations between self-reported scores of psychosocial measures of depression, anxiety, and stress assessed by validated questionnaires with markers of inflammation (CRP; IL-6; IL-18), aging (p16INK4a), and endothelial function (ICAM-1, EndoPAT ratio). Significant positive correlations were observed between psychosocial measures and inflammatory markers including CRP, IL-6, and ICAM-1. However, no psychosocial scores were related to endothelial function or gene expression of the aging biomarker p16INK4a. Overall, survivors had endothelial dysfunction with reduced EndoPAT ratios. Psychosocial stress is associated with greater inflammation in breast cancer survivors on AIs, corroborating previous studies in cancer-free populations. The lack of association between psychosocial stress and either endothelial function or aging biomarkers could be due to the already low endothelial function and accelerated aging in our cohort of breast cancer survivors on AIs, though our small sample size limits conclusions. Further work in a larger and more diverse cohort of patients is needed to further understand the relationships among inflammation, aging and endothelial function in breast cancer survivors.

Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer Survivors (The AIM Trial): Rationale, Design, and Methods.

BackgroundObesity is a significant contributor to breast cancer recurrence and mortality. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. Exercise interventions to target chronic inflammation has a potential to improve obesity- and breast cancer-related outcomes; however, no studies have investigated the roles of exercise in modulating adipose tissue inflammation in breast cancer survivors. Also, it is unclear which exercise prescription would be optimal to maximize the outcomes. Therefore, we designed a randomized controlled trial (Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors [AIM] Trial) to examine the mechanisms by which different modalities of exercise impact chronic inflammation as a biomarker of breast cancer prognosis.MethodsThe AIM trial is a prospective, three-armed, phase II randomized controlled trial investigating the effects of a 16-week supervised circuit aerobic and resistance exercise (CARE) program versus a traditional aerobic and resistance exercise (TARE) program and attention control (AC) on adipose tissue inflammation in breast cancer survivors. 276 patients who are diagnosed with stage 0-III breast cancer, post-treatment, sedentary, and centrally obese are randomized to one of the three groups. The CARE and TARE groups participate in thrice-weekly supervised exercise sessions for 16 weeks. The AC group are offered the CARE program after the intervention period. The primary endpoint is adipose tissue inflammation assessed by core biopsy and blood draw. The secondary and tertiary endpoints are sarcopenic obesity, physical fitness and function, and patient reported outcomes. The exploratory outcomes are long-term breast cancer outcomes.DiscussionThis is the first randomized controlled trial examining the effects of exercise on adipose tissue inflammation in obese, breast cancer survivors. Our findings are anticipated to contribute to a better understanding of exercise modalities and mechanisms on adipose tissue inflammation that can potentially improve breast cancer prognosis.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT03091842 identifier [NCT#03091842].

Interrelationship of Seasons With Inflammation, Foods, Cardio-Metabolic Health, and Smoking Status Among Breast Cancer Survivors

Abstract Objectives Seasons can affect human inflammatory status and the occurrence of diseases, and foods may also have differential impacts on inflammation across seasons; however, few studies have investigated whether there are independent and joint impacts of seasons and red meat, fruit and vegetable intakes on inflammation in breast cancer survivors. Methods We conducted a cross-sectional study by leveraging a large cohort, the Women's Healthy Eating and Living (WHEL) study. The WHEL study comprised primarily early stage breast cancer survivors and collected blood samples, dietary intake, demographic, and health status information at baseline. We selected 2919 participants who provided baseline dietary information and had measurement of C-reactive protein (CRP), a general marker of inflammation. Results In our multivariable-adjusted analyses, we found that red meat intakes were positively associated, while fruit and vegetable intakes were inversely associated with CRP; blood collected in the winter season was associated with lower CRP when compared to summer; and increased smoking intensity and body mass index (BMI) as well as having cardio-metabolic conditions (such as heart disease or diabetes) were positively associated with CRP. Furthermore, we examined the joint associations of food intakes and the season of blood draw with CRP in different subgroups. We found that moderate intakes of red meat were associated with a reduction of CRP in winter but not in other seasons; increased intakes of fruit and vegetables were associated with reduced inflammation in most seasons except winter. These associations were observed in most subgroups except past smokers with pack-years 15, in whom we observed no benefit of red meat intakes in winter. Conclusions Our study provides valuable evidence for considering seasonal impacts on inflammation and seasonal food impacts in different subgroups among breast cancer survivors. The results of our study are in line with one of the emphases of the current NIH 2020–2030 nutrition strategy plan—namely, pay attention to what, when, and who should eat. Funding Sources TRDRP.

Exercise-induced modulation of monocytes in breast cancer survivors

BackgroundExercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. ObjectivesThe effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. MethodsEleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. ResultsExercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (−9989, p=0.014), IL-1ß+CD14+CD16+ MFI (−11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (−63, p=0.002) and CD14+CD16+ (−18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. ConclusionsExercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production.

Effects of Diet and Exercise-Induced Weight Loss on Biomarkers of Inflammation in Breast Cancer Survivors: A Systematic Review and Meta-analysis.

Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy balance through exercise and/or caloric restriction, decreases risk of breast cancer recurrence. We investigated the effects of lifestyle modifications (exercise only, or combined caloric restriction and exercise) on adipokines, IL2, IL6, IL8, IL10, C-reactive protein (CRP), and TNFα biomarkers in breast cancer survivors. Searches were completed in June and July of 2019 to identify randomized controlled trials that met inclusion criteria. Weighted mean difference was calculated using random- or fixed-effects models based on the heterogeneity of the studies. 2501 records were identified, with 30 ultimately meeting inclusion criteria of the systematic review; 21 studies provided data suitable for meta-analysis. We observed leptin levels were significantly reduced in the exercise-only group compared with sedentary control [WMD -5.66; 95% confidence interval (CI), -11.0 to -0.33; P = 0.04]. Leptin may be a primary mediator of exercise-induced improvements in breast cancer recurrence. This is the first review and meta-analysis to examine combined exercise and caloric restriction programs in breast cancer survivors. Future studies should further examine combined programs and their efficacy for altering leptin.

Interrelationship of Seasons with Inflammation, Red Meat, Fruit, and Vegetable Intakes, Cardio-Metabolic Health, and Smoking Status among Breast Cancer Survivors.

Seasons can affect human inflammatory status and the occurrence of diseases, and foods may also have differential impacts on inflammation across seasons; however, few studies have investigated whether there are independent and joint impacts of seasons and red meat, fruit and vegetable intakes on inflammation in breast cancer survivors. We conducted a cross-sectional study by leveraging a large cohort, the Women’s Healthy Eating and Living (WHEL) study. The WHEL study comprised primarily early stage breast cancer survivors and collected blood samples, dietary intake, demographic, and health status information at baseline. We selected 2919 participants who provided baseline dietary information and had measurement of C-reactive protein (CRP), a general marker of inflammation. In our multivariable-adjusted analyses, we found that red meat intakes were positively associated, while fruit and vegetable intakes were inversely associated with CRP; blood collected in the winter season was associated with lower CRP when compared to summer; and increased smoking intensity and body mass index (BMI) as well as having cardio-metabolic conditions (such as heart disease or diabetes) were positively associated with CRP. Furthermore, we examined the joint associations of food intakes and the season of blood draw with CRP in different subgroups. We found that moderate intakes of red meat were associated with a reduction of CRP in winter but not in other seasons; increased intakes of fruit and vegetables were associated with reduced inflammation in most seasons except winter. These associations were observed in most subgroups except past smokers with pack-years ≥ 15, in whom we observed no benefit of red meat intakes in winter. Our study provides valuable evidence for considering seasonal impacts on inflammation and seasonal food impacts in different subgroups among breast cancer survivors. The results of our study are in line with one of the emphases of the current NIH 2020–2030 nutrition strategy plan—namely, pay attention to what, when, and who should eat.

Neural responses to threat and reward and changes in inflammation following a mindfulness intervention

ObjectiveMindfulness meditation has been shown to reduce distress and increase well-being among individuals with chronic disease, including breast cancer survivors. However, the neural correlates of these changes and their links with inflammatory biology are not yet known. The present study examined whether a mindfulness meditation intervention was associated with changes in neural responses to threat and reward from pre- to post-intervention, and whether those neural changes were associated with changes in markers of inflammation in breast cancer survivors. MethodsThis was a single-arm trial of a standardized, validated 6-week mindfulness meditation intervention. Participants were 20 women who had been diagnosed and treated for early-stage breast cancer. Participants provided peripheral blood samples and underwent a 90-minute neuroimaging scan before and after the intervention, with a focus on tasks known to elicit activity in threat- and reward-related neural regions. ResultsThere were significant changes in neural responses to the two tasks of interest from pre to post-intervention (ps < 0.042). Participants showed significant reductions in amygdala activity in response to threatening images and significant increases in ventral striatum activity to rewarding images from pre- to post-intervention. Although changes in amygdala activity were not correlated with inflammatory markers, increases in ventral striatum activity were correlated with decreases in circulating concentrations of the proinflammatory cytokine IL-6 and the inflammatory marker CRP. ConclusionsThese results, while preliminary, suggest that while a mindfulness meditation intervention can alter neural responses to both threat and nonsocial reward-related stimuli, changes in neural reward activity may be more closely linked to changes in circulating levels of inflammation.

Abstract PO-176: Obesity, breast cancer treatment, and systemic inflammation: A cross- sectional analysis of Hispanic and non-Hispanic white breast cancer survivors from New Mexico

Abstract Background: Circulating markers of systemic inflammation have been found to be important long-term prognostic factors for breast cancer (BC). Studies have shown that obesity measured by percent body fat is the most significant predictor of inflammation in BC survivors. Specific BC treatments may also stimulate both local and systemic increases in inflammation. Little is known about the impact of other body size measures and BC treatment effects on inflammation among Hispanic BC survivors, an at-risk population due to their high prevalence of obesity and poor prognosis. Objective: We examined the associations between body size measures, BC treatment, and odds of systemic inflammation measured by soluble tumor necrosis factor receptor-II (sTNF-R2), a circulating pro-inflammatory biomarker, among Hispanic and non-Hispanic white (NHW) women diagnosed with breast cancer (stages I-IIIa) from the New Mexico Health, Eating, Activity, and Lifestyle cohort. Methods: A total of 397 BC survivors (96 Hispanic, 301 NHW) contributed data for the present study. Women with BC diagnosed between July 1996 and March 1999 were ascertained through the National Cancer Institute’s Surveillance Epidemiology and End Results registry in New Mexico. Baseline demographic characteristics, anthropometric measures, and blood samples were collected approximately 5 months post diagnosis by trained interviewers. Plasma levels of sTNF-R2 were assayed and measures were log-transformed to conform to normality. The study outcome of low vs high sTNF-R2 levels was based on the median value. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression models and were stratified by ethnicity. Results: There were higher proportions of women with high compared to low sTNF-R2 levels and the following obesity measures: high percent body fat (≥35%), high body mass index (BMI) (≥30 kg/m2), and high waist-hip ratio (&amp;gt;0.85). No significant differences were observed by sTNF-R2 levels and ethnicity or treatment. In multivariable models, we observed significant positive associations among women with high body fat percentage (compared to &amp;lt; 35%) (OR= 1.62, 95% CI 1.01-2.60) and morbid obesity (BMI ≥35 kg/m2 compared to BMI&amp;lt; 35 kg/m2) (OR= 4.16, 95% CI 1.43-12.10). High waist-hip ratio was not significantly associated with sTNF-R2. While current tamoxifen use was not associated with sTNF-R2, we did find that women who received radiation and chemotherapy were 2 times more likely to have high sTNF-R2 levels compared to women who did not have chemotherapy and radiation (OR= 2.04, 95% CI 1.03-4.01). Our results were not significantly modified by ethnicity. Conclusion: BC survivors with high body fat percentage and extreme BMI have increased odds of systemic inflammation measured by sTNF-R2. Survivors treated with chemotherapy and radiation are also more likely to experience systemic inflammation. Future studies will examine the long-term effects of these associations on poor prognosis. Citation Format: Avonne E. Connor, Kala Visvanathan, Stephanie D. Boone, Kathy B. Baumgartner, Richard N. Baumgartner. Obesity, breast cancer treatment, and systemic inflammation: A cross- sectional analysis of Hispanic and non-Hispanic white breast cancer survivors from New Mexico [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-176.

Relationship satisfaction predicts lower stress and inflammation in breast cancer survivors: A longitudinal study of within-person and between-person effects

BackgroundBreast cancer survivors with elevated inflammation have a greater risk for cancer recurrence, premature mortality, and comorbid disease development. The psychological stress survivors experience when confronted with a breast cancer diagnosis and cancer treatment can heighten inflammation. Identifying factors that reduce stress and inflammation could lead to improvements in survivors’ long-term health. Accordingly, this study examined the health-enhancing effects of romantic relationships—a key health determinant—on breast cancer survivors’ stress and inflammation. MethodsBreast cancer survivors (n = 139, stages 0–IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed self-report questionnaires assessing their romantic relationship satisfaction and perceived stress, and they provided a blood sample for serum markers of inflammation at each visit. The longitudinal design allowed for examination within and between survivors. We conducted multilevel mediation analyses to assess how changes in survivors’ relationship satisfaction were related to changes in stress and inflammation from visit to visit (i.e., within-person effects), as well as how the average effects of relationship satisfaction were associated with average stress and inflammation levels throughout the study (i.e., between-person effects). ResultsAt the within-person level, at visits in which survivors were more satisfied with their relationships, they also perceived less stress, which in turn was related to lower than their own average levels of serum C-reactive protein and proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β). At the between-person level, survivors who had greater relationship satisfaction throughout the study had lower perceived stress, which was linked to lower levels of inflammation. ConclusionBreast cancer survivors in satisfying romantic relationships felt less stressed and in turn had lower inflammation throughout cancer treatment. This study illustrates the utility of a within-person approach to not only consider the average effects of relationship satisfaction, but also how changes in their own relationship satisfaction impact stress and inflammation over time. Our findings demonstrate important psychological and immunological pathways through which satisfying relationships may promote breast cancer survivors’ long-term health.

Diet Quality, Inflammation, and Quality of Life in Breast Cancer Survivors: A Cross-Sectional Analysis of Pilot Study Data

BackgroundModifiable lifestyle factors, such as diet quality, could reduce inflammation and improve quality of life (QOL) in breast cancer survivors, but data are inconclusive. ObjectiveTo determine whether diet quality, as measured by Healthy Eating Index-2010 (HEI-2010) score, is associated with inflammation, health status, or functional outcomes affecting QOL in survivors of early-stage breast cancer. DesignThis is a cross-sectional, secondary analysis of baseline data collected from breast cancer survivors after completion of primary therapy and before random assignment to a pilot nutritional intervention aimed at reducing side effects of aromatase inhibitor treatment. Participants/settingParticipants were 44 postmenopausal women with stage I to III endocrine receptor–positive breast cancer receiving outpatient care at a midwestern cancer center between November 2011 and October 2013. Main outcome measuresPrimary outcomes were serum proinflammatory cytokines (interleukin-6 [IL-6], IL-17, and tumor necrosis factor-α receptor 2 [TNFR-2]). Secondary outcomes included QOL measured by the Stanford Health and Disability Questionnaire and the Functional Assessment of Cancer Therapy–Breast with Endocrine Subscale. Statistical analyses performedPearson correlation coefficients (r) and linear regression models were used to evaluate the relationship of dietary variables with inflammatory cytokines and QOL measures. ResultsA higher overall HEI-2010 score (healthier diet) was associated with lower IL-6 (r=−0.46; P=0.002) and TNFR-2 (r=−0.41; P=0.006); however, associations were attenuated by body mass index (BMI) (IL=6 [r=−0.26; P=0.10]; TNFR-2 [r=−0.30; P=0.06]). In women with prior chemotherapy, a higher HEI-2010 score was strongly associated with lower IL-6 (r=−0.67; P=0.009) and TNFR-2 (r=−0.59; P=0.03) after BMI adjustment. There were no significant correlations between HEI-2010 score and QOL measures after adjustment for BMI. ConclusionsThese data suggest the need for more rigorous investigation into the relationship of diet quality, BMI, and inflammation in breast cancer survivors.

Adipose tissue inflammation in breast cancer survivors: effects of a 16-week combined aerobic and resistance exercise training intervention.

Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. Obesity stimulates cancer progression through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular, the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter ATM phenotype in obese postmenopausal breast cancer survivors. Twenty obese postmenopausal breast cancer survivors were randomized to a 16-week aerobic and resistance exercise (EX) intervention or delayed intervention control (CON). The EX group participated in 16weeks of supervised exercise sessions 3 times/week. Participants provided fasting blood, dual-energy X-ray absorptiometry (DXA), and superficial subcutaneous abdominal adipose tissue biopsies at baseline and following the 16-week study period. EX participants experienced significant improvements in body composition, cardiometabolic biomarkers, and systemic inflammation (all p<0.03 vs. CON). Adipose tissue from EX participants showed a significant decrease in ATM M1 (p<0.001), an increase in ATM M2 (p<0.001), increased adipose tissue secretion of anti-inflammatory cytokines such as adiponectin, and decreased secretion of the pro-inflammatory cytokines IL-6 and TNF- α (all p<0.055). A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence.

Abstract 985: Adipose tissue inflammation in breast cancer survivors: Effects of a 16-week aerobic and resistance exercise intervention

Abstract Background and Purpose: Obesity is a leading modifiable contributor to breast cancer mortality due to its association with increased recurrence and decreased overall survival rate. There are over 2.5 million breast cancer survivors, 64% of whom are overweight/obese (BMI &amp;gt;25 kg/m2). A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in white adipose tissue, leading to accumulation of adipose tissue macrophages (ATMs), in particular the pro-inflammatory M1 phenotype macrophage. Exercise has been shown to reduce M1 ATMs, and increase the more anti-inflammatory M2 ATMs in obese adults. The purpose of this study was to determine whether a 16-week exercise intervention would positively alter adipose tissue inflammation by changing ATM phenotype and cytokine secretion in obese postmenopausal breast cancer survivors. Experimental Design: Twenty obese postmenopausal breast cancer survivors were recruited from USC and randomized to either the exercise (EX) or control (CON) group. The EX group participated in 16 weeks of supervised exercise sessions 3 times/week. Sessions included total-body resistance training consisting of 8 exercises with a rest period of 45 seconds between each set of resistance exercise followed by 30 minutes of moderate-vigorous intensity (65-80% HRmax) aerobic exercise. The CON group was asked to maintain their current activity levels. Superficial subcutaneous abdominal adipose tissue biopsies were performed at baseline and following the 16-week study period. Adipose tissue samples were analyzed using fluorescence-activated cell sorting (FACS) to characterize ATM characterization (M1 vs M2). Portions (~100 mg) of each biopsy were incubated in media overnight to measure cytokine secretion. A 2x2 (group x time) repeated measures ANOVA was used to evaluate changes in adipose tissue and systemic inflammation. Summary of Results: At baseline, there were no group differences (p&amp;gt;0.05) in age (55.1±5.2 yrs), BMI (34.4±7.5 kg/m2), percent body fat (36.2±4.9%), or ATM M1 (25.4±6.7%) and M2 (4.2±0.9%) levels. EX was associated with a significant decrease in ATM M1 (-18.8±7.3%) and increase in ATM M2 (9.6±1.6%; p&amp;lt;0.01). EX increased adipose tissue secretion of the anti-inflammatory cytokines, adiponectin (14.6±5.2%), IL-12 p40 (2.4±0.8), IL-12 p70 (2.8±1.8%) and decreased secretion of IL-6 (-4.8±2.0%), and TNF-a (-2.0±0.7; p&amp;lt;0.01). The CON group did not experience any changes in ATM characterization and cytokine secretion during the study period (p&amp;gt;0.01). Conclusions: A 16-week aerobic and resistance exercise intervention attenuates adipose tissue inflammation in obese postmenopausal breast cancer survivors. Future large randomized controlled trials are warranted to investigate the impact of exercise-induced reductions in adipose tissue inflammation and breast cancer recurrence. Citation Format: Christina M. Dieli-Conwright, Jean Hughes-Parmentier, Kyuwan Lee, Darcy Spicer, Wendy Mack, Fred Sattler, Steven D. Mittelman. Adipose tissue inflammation in breast cancer survivors: Effects of a 16-week aerobic and resistance exercise intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 985. doi:10.1158/1538-7445.AM2017-985

Breast Cancer Survivors, Common Markers of Inflammation, and Exercise: A Narrative Review.

Exercise may help positively improve inflammatory marker levels, therefore promoting better outcomes in breast cancer survivors. This narrative review is intended to provide an overview between inflammation and breast cancer, in addition to the effects exercise may have on common inflammatory markers that have been examined in both healthy populations and breast cancer survivors throughout the literature. The inconsistencies and gaps in the literature addressed may be important for future research to further understand the relationship between exercise and inflammation, as well as the underlying biological mechanisms that are responsible for these changes. For the purpose of organization, this review is structured into the following sections: (1) Breast Cancer Facts, Treatment-Related Side Effects, and General Exercise Benefits; (2) Effects of Exercise on Markers of Inflammation in Cancer-Free Populations; (3) Cancer and Markers of Inflammation; (4) Effects of Exercise on Markers of Inflammation in Breast Cancer Survivors; and (5) Conclusions.

Distress and quality of life in an ethnically diverse sample awaiting breast cancer surgery

Poor breast cancer-related quality of life is associated with flattened cortisol rhythms and inflammation in breast cancer survivors and women with advanced disease. We explored the associations of cancer-specific distress (Impact of Events Scale), mood (Profile of Mood States), activity/sleep (wake after sleep onset, 24-hour autocorrelation coefficient) and cortisol (diurnal slope) circadian rhythms, and inflammation (interleukin-6) with quality of life (Functional Assessment of Cancer Therapy-Breast) among patients awaiting breast cancer surgery ( N = 57). Models were adjusted for differences in age and cancer stage. Distress and mood disturbance were significantly correlated with lower quality of life. Ethnic differences in the relationship between distress and mood disturbance with global quality of life and subscales of quality of life were observed. Actigraphic measures showed that in comparison with non-Hispanic patients, African Americans had significantly poorer activity/sleep (wake after sleep onset, 24-hour autocorrelation coefficient). Circadian disruption and inflammation were not associated with quality of life. Physiological dysregulation and associated comorbidities may take time to develop over the course of disease and treatment.

The Effect of Exercise Training on Mediators of Inflammation in Breast Cancer Survivors: A Systematic Review with Meta-analysis.

Several sources of evidence indicate that exercise during and after breast cancer could positively modulate the tumor microenvironment. This meta-analysis aimed to determine the effects of exercise training on mediators of inflammation in breast cancer survivors. We searched for randomized controlled trials published from January 1990 to March 2014. An inverse variance method of meta-analysis was performed using a random effects model in the presence of statistical heterogeneity. Eight high-quality trials (n = 478) were included. Exercise improved the serum concentrations of IL6 [weighted mean difference (WMD) = -0.55 pg/mL; 95% confidence interval (CI), -1.02 to -0.09], TNFα (WMD = -0.64 pg/mL; 95% CI, -1.21 to -0.06), IL8 (MD = -0.49 pg/mL; 95% CI, -0.89 to -0.09), and IL2 (WMD = 1.03 pg/mL; 95% CI, 0.40 to 1.67). No significant differences were found in the serum concentrations of C-reactive protein (WMD = -0.15; 95% CI, -0.56 to 0.25) or IL10 (WMD = 0.41; 95% CI, -0.18 to 1.02). Exercise training positively modulates chronic low-grade inflammation in women with breast cancer, which may impact upon carcinogenic mechanisms and the tumor microenvironment. These findings align with the other positive effects of exercise for breast cancer survivors, reinforcing the appropriateness of exercise prescription in this population. Cancer Epidemiol Biomarkers Prev; 25(7); 1009-17. ©2016 AACR.