Body mass index associated with genome-wide methylation in breast tissue.

Gene expression studies indicate that body mass index (BMI) is associated with molecular pathways involved in inflammation, insulin-like growth factor activation, and other carcinogenic processes in breast tissue. The goal of this study was to determine whether BMI is associated with gene methylation in breast tissue and to identify pathways that are commonly methylated in association with high BMI. Epigenome-wide methylation profiles were determined using the Illumina HumanMethylation450 BeadChip array in the non-diseased breast tissue of 81 women undergoing breast surgery between 2009 and 2013 at the University of North Carolina Hospitals. Multivariable, robust linear regression was performed to identify methylation sites associated with BMI at a false discovery rate q value <0.05. Gene expression microarray data was used to identify which of the BMI-associated methylation sites also showed correlation with gene expression. Gene set enrichment analysis was conducted to assess which pathways were enriched among the BMI-associated methylation sites. Of the 431,568 methylation sites analyzed, 2573 were associated with BMI (q value <0.05), 57 % of which showed an inverse correlation with BMI. Pathways enriched among the 2573 probe sites included those involved in inflammation, insulin receptor signaling, and leptin signaling. We were able to map 1251 of the BMI-associated methylation sites to gene expression data, and, of these, 226 (18 %) showed substantial correlations with gene expression. Our results suggest that BMI is associated with genome-wide methylation in non-diseased breast tissue and may influence epigenetic pathways involved in inflammatory and other carcinogenic processes.

Racial differences in physical activity among breast cancer survivors: implications for breast cancer care.

BACKGROUND: Physical activity after breast cancer diagnosis is associated with improved survival. The current study examined levels of and changes in physical activity after breast cancer diagnosis, overall and by race. METHODS: Phase 3 of the Carolina Breast Cancer Study assessed both pre- and postdiagnosis physical activity levels in a cohort of 1735 women aged 20 years to 74 years who were diagnosed with invasive breast cancer between 2008 and 2011 in 44 counties of North Carolina. Logistic regression and analysis of variance were used to examine whether demographic, behavioral, and clinical characteristics were associated with activity levels. RESULTS: Only 35% of study participants met current physical activity guidelines after diagnosis with breast cancer. A decrease in activity after diagnosis was reported by 59% of patients, with the average study participant reducing their activity by 15 metabolic equivalent task (MET) hours (95% confidence interval [95% CI], 12 MET hours-19 MET hours). After adjustment for potential confounders, when compared with white women, African American women were less likely to meet national physical activity guidelines after diagnosis (odds ratio, 1.38; 95% CI, 1.01-1.88) and reported less weekly postdiagnosis physical activity (12 MET hours vs 14 MET hours; P = .13). In adjusted stratified analyses, receipt of treatment was found to be significantly associated with postdiagnosis activity in African American women (P < 0.01). CONCLUSIONS: Despite compelling evidence demonstrating the benefits of physical activity after a diagnosis of breast cancer, it is clear that more work needs to be done to promote physical activity in patients with breast cancer, especially among African American women.

A Systematic Literature Review of Health Center Efforts to Address Social Determinants of Health.

Health centers (HCs) play a crucial and integral role in addressing social determinants of health (SDOH) among vulnerable and underserved populations, yet data on SDOH assessment and subsequent actions is limited. We conducted a systematic review to understand the existing evidence of integration of SDOH into HC primary-care practices. Database searches yielded 3,516 studies, of which 41 articles met the inclusion criteria. A majority of studies showed that HCs primarily captured patient-level rather than community-level SDOH data. Studies also showed that HCs utilized SDOH in electronic health records but capabilities varied widely. A few studies indicated that HCs measured health-related outcomes of integrating SDOH data. The review highlighted that many knowledge gaps exist in the collection, use, and assessment of impact of these data on outcomes, and future research is needed to address this knowledge gap.

The Relative Contribution of Social Determinants of Health Among Health Resources and Services Administration-Funded Health Centers.

Frameworks for identifying and assessing social determinants of health (SDOH) are effective for developing long-term societal policies to promote health and well-being, but may be less applicable in clinical settings. The authors compared the relative contribution of a specific set of SDOH indicators with several measures of health status among patients served by health centers (HCs). The 2014 Health Center Patient Survey was used to identify a sample of HC patient adults 18 years and older that reported the HC as their usual source of care (n = 5024). The authors examined the relationship between SDOH indicators organized in categories (health behaviors, access and utilization, social factors, economic factors, quality of care, physical environment) with health status measures (fair or poor health, diabetes, hypertension, cardiovascular disease, depression, or anxiety) using logistic regressions and predicted probabilities. Findings indicated that access to care and utilization indicators had the greatest relative contribution to all health status measures, but the relative contribution of other SDOH indicators varied. For example, access indicators had the highest predicted probability in the model with fair or poor health as the dependent variable (72.4%) and the model with hypertension as the dependent variable (47.4%). However, the second highest predicted probability was for social indicators (54.1%) in the former model and physical environment (44.7%) indicators in the latter model. These findings have implications for HCs that serve as the primary point of access to medical care in underserved communities and to mitigate SDOH particularly for patients with diabetes, depression, or anxiety.

Patient-Provider Communication and Adherence to Cholesterol Management Advice: Findings from a Cross-Sectional Survey.

High cholesterol is a preventable risk factor for heart disease. This study examines which aspects of patient-provider communication are associated with patient report of increased adherence to cholesterol management advice in a diverse, low-income patient population accessing the health care safety net, using the 2014 Health Center Patient Survey. Patient-provider communication measures included patient report of: how often a provider listened carefully, gave easy-to-understand information, knew important information about the patient's medical history, showed respect, and spent enough time with the patient. Outcome measures were patient report of following provider advice to eat fewer high fat or high cholesterol foods, manage weight, increase physical activity, or take prescribed medicine. In adjusted analyses, when patients perceived their provider always knew their medical history, patients were more likely to report taking prescribed medication (adjusted odds ratio [aOR]: 3.2; 95% confidence interval [CI]: 1.6, 6.6). Knowledge of medical history (aOR: 2.8, 95% CI: 1.4, 5.8), spending enough time (aOR: 2.3, 95% CI: 1.2, 4.4), and providing easily understandable information (aOR: 2.2, 95% CI: 1.0, 4.7) were significantly associated with report of following physical activity advice. Knowledge of medical history (aOR: 2.3, 95% CI: 1.0, 5.2) and providing easily understandable information (aOR: 3.3, 95% CI: 1.4, 7.9) were significantly associated with report of following weight management advice. This study indicates different components of patient-provider communication influence patient adherence to lifestyle modification advice and medication prescription. These results suggest a tailored approach to optimize the impact of patient-provider communication on cholesterol management advice adherence.

Mental Health Staffing at HRSA-Funded Health Centers May Improve Access to Care.

OBJECTIVE: The study objective was to examine the association between mental health staffing at health centers funded by the Health Resources and Services Administration (HRSA) and patients' receipt of mental health treatment. METHODS: Data were from the 2014 HRSA-funded Health Center Patient Survey and the 2013 Uniform Data System. Colocation of any mental health staff, including psychiatrists, psychologists, and other licensed staff, was examined. The outcomes of interest were whether a patient received any mental treatment and received any such treatment on site (at the health center). Analyses were conducted with multilevel generalized structural equation logistic regression models for 4,575 patients ages 18-64. RESULTS: Patients attending health centers with at least one mental health full-time equivalent (FTE) per 2,000 patients had a higher predicted probability of receiving mental health treatment (32%) compared with those attending centers with fewer than one such FTE (24%) or no such staffing (22%). Among patients who received this treatment, those at health centers with no staffing had a significantly lower predicted probability of receiving such treatment on site (28%), compared with patients at health centers with fewer than one such FTE (49%) and with at least one such FTE (65%). The predicted probability of receiving such treatment on site was significantly higher if there was a colocated psychiatrist versus no psychiatrist (58% versus 40%). CONCLUSIONS: Colocating mental health staff at health centers increases the probability of patients' access to such treatment on site as well as from off-site providers.

Geographic disparities in cancer screening and fatalism among a nationally representative sample of US adults.

BACKGROUND: Cancer screening in the USA is suboptimal, particularly for individuals living in vulnerable communities. This study aimed to understand how rurality and racial segregation are independently and interactively associated with cancer screening and cancer fatalism. METHODS: We used data from a nationally representative sample of adults (n=17 736) from National Cancer Institute's Health Information National Trends Survey, 2011-2017, including cancer screening (colorectal, breast, cervical, prostate) among eligible participants and cancer fatalism. These data were linked to county-level metropolitan status/rurality (US Department of Agriculture) and racial segregation (US Census). We conducted multivariable analyses of associations of geographic variables with screening and fatalism. RESULTS: Breast cancer screening was lower in rural (92%, SE=1.5%) than urban counties (96%, SE=0.5%) (adjusted OR (aOR)=0.52, 95% CI 0.31 to 0.87). Colorectal cancer screening was higher in highly segregated (70%, SE=1.0%) than less segregated counties (65%, SE=1.7%) (aOR=1.28, 95% CI 1.04 to 1.58). Remaining outcomes did not vary by rurality or segregation, and these variables did not interact in their associations with screening or fatalism. CONCLUSION: Similar to previous studies, breast cancer screening was less common in rural areas. Contrary to expectations, colorectal cancer screening was higher in highly segregated counties. More research is needed on the influence of geography on cancer screening and beliefs, and how access to facilities or information may mediate these relationships.

Obesity-Associated Alterations in Inflammation, Epigenetics, and Mammary Tumor Growth Persist in Formerly Obese Mice.

Using a murine model of basal-like breast cancer, we tested the hypothesis that chronic obesity, an established breast cancer risk and progression factor in women, induces mammary gland epigenetic reprogramming and increases mammary tumor growth. Moreover, we assessed whether the obesity-induced epigenetic and protumor effects are reversed by weight normalization. Ovariectomized female C57BL/6 mice were fed a control diet or diet-induced obesity (DIO) regimen for 17 weeks, resulting in a normal weight or obese phenotype, respectively. Mice on the DIO regimen were then randomized to continue the DIO diet or were switched to the control diet, resulting in formerly obese (FOb) mice with weights comparable with control mice. At week 24, all mice were orthotopically injected with MMTV-Wnt-1 mouse mammary tumor cells. Mean tumor volume, serum IL6 levels, expression of proinflammatory genes in the mammary fat pad, and mammary DNA methylation profiles were similar in DIO and FOb mice and higher than in controls. Many of the genes found to have obesity-associated hypermethylation in mice were also found to be hypermethylated in the normal breast tissue of obese versus nonobese human subjects, and nearly all of these concordant genes remained hypermethylated after significant weight loss in the FOb mice. Our findings suggest that weight normalization may not be sufficient to reverse the effects of chronic obesity on epigenetic reprogramming and inflammatory signals in the microenvironment that are associated with breast cancer progression. Cancer Prev Res; 9(5); 339-48. ©2016 AACR.

Body mass index is associated with gene methylation in estrogen receptor-positive breast tumors.

BACKGROUND: Although obesity is associated with breast cancer incidence and prognosis, the underlying mechanisms are poorly understood. Identification of obesity-associated epigenetic changes in breast tissue may advance mechanistic understanding of breast cancer initiation and progression. The goal of this study, therefore, was to investigate associations between obesity and gene methylation in breast tumors. METHODS: Using the Illumina GoldenGate Cancer I Panel, we estimated the association between body mass index (BMI) and gene methylation in 345 breast tumor samples from phase I of the Carolina Breast Cancer Study, a population-based case-control study. Multivariable linear regression was used to identify sites that were differentially methylated by BMI. Stratification by tumor estrogen receptor (ER) status was also conducted. RESULTS: In the majority of the 935 probes analyzed (87%), the average beta value increased with obesity (BMI ≥ 30). Obesity was significantly associated with differential methylation (FDR q < 0.05) in just two gene loci in breast tumor tissue overall and in 21 loci among ER-positive tumors. Obesity was associated with methylation of genes that function in immune response, cell growth, and DNA repair. CONCLUSIONS: Obesity is associated with altered methylation overall, and with hypermethylation among ER-positive tumors in particular, suggesting that obesity may influence the methylation of genes with known relevance to cancer. Some of these differences in methylation by obese status may influence levels of gene expression within breast cells. IMPACT: If our results are validated, obesity-associated methylation sites could serve as targets for prevention and treatment research. Cancer Epidemiol Biomarkers Prev; 24(3); 580-6. ©2015 AACR.

Racial variation in breast tumor promoter methylation in the Carolina Breast Cancer Study.

BACKGROUND: African American (AA) women are diagnosed with more advanced breast cancers and have worse survival than white women, but a comprehensive understanding of the basis for this disparity remains unclear. Analysis of DNA methylation, an epigenetic mechanism that can regulate gene expression, could help to explain racial differences in breast tumor clinical biology and outcomes. METHODS: DNA methylation was evaluated at 1,287 CpGs in the promoters of cancer-related genes in 517 breast tumors of AA (n = 216) or non-AA (n = 301) cases in the Carolina Breast Cancer Study (CBCS). RESULTS: Multivariable linear regression analysis of all tumors, controlling for age, menopausal status, stage, intrinsic subtype, and multiple comparisons [false discovery rate (FDR)], identified seven CpG probes that showed significant (adjusted P < 0.05) differential methylation between AAs and non-AAs. Stratified analyses detected an additional four CpG probes differing by race within hormone receptor-negative (HR(-)) tumors. Genes differentially methylated by race included DSC2, KCNK4, GSTM1, AXL, DNAJC15, HBII-52, TUSC3, and TES; the methylation state of several of these genes may be associated with worse survival in AAs. TCGA breast tumor data confirmed the differential methylation by race and negative correlations with expression for most of these genes. Several loci also showed racial differences in methylation in peripheral blood leukocytes (PBL) from CBCS cases, indicating that these variations were not necessarily tumor-specific. CONCLUSIONS: Racial differences in the methylation of cancer-related genes are detectable in both tumors and PBLs from breast cancer cases. IMPACT: Epigenetic variation could contribute to differences in breast tumor development and outcomes between AAs and non-AAs.

Age/race differences in HER2 testing and in incidence rates for breast cancer triple subtypes: a population-based study and first report.

BACKGROUND: Although US year 2000 guidelines recommended characterizing breast cancers by human epidermal growth factor receptor 2 (HER2), national cancer registries do not collect HER2, rendering a population-based understanding of HER2 and clinical "triple subtypes" (estrogen receptor [ER] / progesterone receptor [PR] / HER2) largely unknown. We document the population-based prevalence of HER2 testing / status, triple subtypes and present the first report of subtype incidence rates. METHODS: Medical records were searched for HER2 on 1842 metropolitan Atlanta females diagnosed with breast cancer during 2003-2004. HER2 testing/status and triple subtypes were analyzed by age, race/ethnicity, tumor factors, socioeconomic status, and treatment. Age-adjusted incidence rates were calculated. RESULTS: Over 90% of cases received HER2 testing: 12.6% were positive, 71.7% negative, and 15.7% unknown. HER2 testing compliance was significantly better for women who were younger, of Caucasian or African-American descent, or diagnosed with early stage disease. Incidence rates (per 100,000) were 21.1 for HER2+ tumors and 27.8 for triple-negative tumors, the latter differing by race (36.3 and 19.4 for black and white women, respectively). CONCLUSIONS: HER2 recommendations are not uniformly adhered to. Incidence rates for breast cancer triple subtypes differ by age/race. As biologic knowledge is translated into the clinical setting eg, HER2 as a biomarker, it will be incumbent upon national cancer registries to report this information. Incidence rates cautiously extrapolate to an annual burden of 3000 and 17,000 HER2+ tumors for black and white women, respectively, and triple-negative tumors among 5000 and 16,000 respectively. Testing, rate, and burden variations warrant population-based in-depth exploration and clinical translation.