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Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer.

ABSTRACT: Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance.WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) of the breast. Two independent groups were examined in cross-sectional (cohort 1) and retrospective (cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n = 10) or treatment (n = 90). Metabolic syndrome-associated circulating factors were compared by CLS-B status. The association between CLS of the breast and the metabolic syndrome was validated in cohort 2, which included 127 women who developed metastatic breast cancer. Distant recurrence-free survival (dRFS) was compared by CLS-B status.In cohorts 1 and 2, breast WAT inflammation was detected in 52 of 100 (52%) and 52 of 127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and IL6 and lower high-density lipoprotein cholesterol and adiponectin (P < 0.05) in cohort 1. In cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P < 0.05). Compared with patients without breast WAT inflammation, the adjusted HR for dRFS was 1.83 (95% CI, 1.07-3.13) for patients with inflammation.WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis. Clin Cancer Res; 22(9); 2283-9. ©2015 AACR.

SUBMITTER: Iyengar NM

PROVIDER: S-EPMC4854755 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer.

Iyengar Neil M NM Zhou Xi Kathy XK Gucalp Ayca A Morris Patrick G PG Howe Louise R LR Giri Dilip D DD Morrow Monica M Wang Hanhan H Pollak Michael M Jones Lee W LW Hudis Clifford A CA Dannenberg Andrew J AJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20151228 9

<h4>Purpose</h4>Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance.<h4>Experimental design</h4>WAT inflammation was defined by the presence of dead/dying adipocytes surro ...[more]

PMID: 26712688

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Project description:ImportanceAdvances in the evaluation and treatment of breast cancer have made the clinical decision-making context much more complex. A second opinion from a medical oncologist may facilitate decision making for women with breast cancer, yet little is known about second opinion use.ObjectiveTo investigate the patterns and correlates of second opinion use and the effect on chemotherapy decisions.Design, setting, and participantsA total of 1901 women newly diagnosed with stages 0 to II breast cancer between July 2013 and September 2014 (response rate, 71.0%) were accrued through 2 population-based Surveillance, Epidemiology, and End Results registries (Georgia and Los Angeles County, California) and surveyed about their experiences with medical oncologists, decision making, and chemotherapy use.Main outcomes and measuresFactors associated with second opinion use were evaluated using logistic regression. Also assessed was the association between second opinion and chemotherapy use, adjusting for chemotherapy indication and propensity for receiving a second opinion. Multiple imputation and weighting were used to account for missing data.ResultsA total of 1901 patients with stage I to II breast cancer (mean [SD] age, 61.6 [11.0] years; 1071 [56.3%] non-Hispanic white) saw any medical oncologist. Analysis of multiply imputed, weighted data (mean n = 1866) showed that 168 (9.8%) (SE, 0.74%) received a second opinion and 54 (3.2%) (SE, 0.47%) received chemotherapy from the second oncologist. Satisfaction with chemotherapy decisions was high and did not differ between those who did (mean [SD], 4.3 [0.08] on a 1- to 5-point scale) or did not (4.4 [0.03]) obtain a second opinion (P = .29). Predictors of second opinion use included college education vs less education (odds ratio [OR], 1.85; 95% CI, 1.24-2.75), frequent use of internet-based support groups (OR, 2.15; 95% CI, 1.12-4.11), an intermediate result on the 21-gene recurrence score assay (OR, 1.85; 95% CI, 1.11-3.09), and a variant of uncertain significance on hereditary cancer genetic testing (OR, 3.24; 95% CI, 1.09-9.59). After controlling for patient and tumor characteristics, second opinion use was not associated with chemotherapy receipt (OR, 1.04; 95% CI, 0.71-1.52).Conclusions and relevanceSecond opinion use was low (<10%) among patients with early-stage breast cancer, and high decision satisfaction regardless of second opinion use suggests little unmet demand. Along with educational level and use of internet support groups, uncertain results on genomic testing predicted second opinion use. Patient demand for second opinions may increase as more complex genomic tests are disseminated.

Dataset Information

Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer.

Publications

Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer.

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