Exploration of Stress and Inflammatory Biomarkers Among Non-Hispanic Black and Hispanic Cancer Survivors.

OBJECTIVES: To evaluate associations among social determinants of health (SDOH), stress, interleukin-6 (IL-6), and quality of life among non-Hispanic Black and Hispanic cancer survivors. SAMPLE & SETTING: Individuals who had completed cancer treatment and did not identify as White (N = 46) were recruited through community partnerships in western Massachusetts and a state cancer registry. METHODS & VARIABLES: This descriptive cross-sectional study used questionnaires and morning salivary samples to collect data between June 2022 and September 2023. RESULTS: Most participants were breast cancer survivors, were female, identified as African American or Black, and reported moderate levels of stress and low physical activity. Cortisol levels were higher among African American or Black participants, those with lower body mass index, and those with less consumption of fruit and vegetables. Higher symptom experience was associated with higher IL-6 levels. No associations were identified between IL-6 and cortisol or perceived stress and cortisol levels. IMPLICATIONS FOR NURSING: Incorporating SDOH in self-reported outcomes, including health behaviors and associated biologic indicators, can facilitate early identification and interventions to improve symptom experience and health outcomes of cancer survivors.

A Latent Class Analysis of Family Eating Behaviors and Home Environment Habits on Preschool-Aged Children's Body Mass Index.

Background: The etiology of obesity is multifaceted, with multiple risk factors occurring during early childhood (e.g., fast food frequency, eating dinner as a family, TV in the bedroom). Many past studies have largely considered obesity risk factors in isolation, when in reality, the risk factors likely cluster together. A latent class analysis can be used to identify patterns in child eating behaviors, parent feeding behaviors, and household habits among preschool-aged children and their families to identify distinct, heterogenous classes and to determine if classes are associated with overweight and obesity. Methods: We used data from a community-based study of 624 three- to five-year-old children and a parent in New Hampshire, from March 2014 to October 2015. Parent-reported data were used to determine frequency of eating behaviors and household habits. Height and weight were objectively measured. Results: Four classes were identified; Class 1: "Healthy/Mildly accommodating," Class 2: "Healthy/Accommodating," Class 3: "Moderately healthy/Moderately accommodating," and Class 4: "Least healthy/Least accommodating." Compared with Class 1, children in Class 4 had increased odds of being overweight or obese [adjusted odds ratio (aOR): 1.64, 95% confidence interval (CI): 1.13-2.15], whereas Classes 2 and 3 were not associated with BMI (Class 2: aOR: 1.24, 95% CI: 0.62-1.86; Class 3: aOR: 1.31, 95% CI: 0.81-1.81). Conclusion: Study findings highlight that child-parent interactions around meals differentially relate to children's weight status given the context of children's eating habits. Most important, our study findings confirm the importance of adapting multiple healthy habits within the home social and physical environment to offset obesity risk in young children.

Children's Perception of Food Marketing Across Digital Media Platforms.

Introduction: Exposure to food marketing increases the risk of poor diet. Children's perception and interpretation of food marketing across digital media platforms is understudied. Children aged 9-11 years are uniquely susceptible to food marketing because children may watch content alone, and it is unclear whether embedded ads are decipherable by children (e.g., social media influencers) and if children are receptive to advertisements. Methods: The authors collected data from 21 child-parent dyads in 2022 to fill this gap. Children were interviewed about their food marketing exposure and media use and were asked to share their perspectives on food advertisements. Parents completed a survey for household digital devices, demographics, and perception of their child's food advertising knowledge. Results: This study found that all children generally recognized direct food advertisements, could describe them with varying levels of confidence, and shared examples. Despite self-identifying ads and understanding the intent of advertising, many children are still receptive to advertisements on the basis of engaging content (e.g., liking the ads as entertainment, watching ads even when given the chance to skip the ad) and the food items marketed (e.g., liking the taste of foods). Conclusions: These findings suggest that knowledge of advertisement exposure and intent of advertising are not sufficient to reduce receptiveness of unhealthy food ad exposure. Additional research on the potential impacts of embedded ads, such as through social media influencers, is needed to understand children's interaction with the current digital media landscape.

Factors Correlated With Ultra-Processed Food (UPF) Intake in Preschool-Aged Children and Association With Weight.

OBJECTIVE: Understand the correlates of ultra-processed food (UPF) intake and examine the association of UPF on body mass index in children aged 3-5 years. DESIGN: Secondary analysis of a prospective cohort of 3-5-year-olds/parent, followed 1-year between March 2014 and October 2016. Usual UPF intake from 2 3-day food records completed 1 year apart, a standardized nutrient database customized with child-specific foods, and a NOVA food classification system was used. Child/parent characteristics and media use were measured via parent-reported surveys. Child weight/height objectively measured. SETTING: New Hampshire community. PARTICIPANTS: Six hundred and sixty-seven parent-child dyads were screened, and 624 were enrolled with 90% follow-up. MAIN OUTCOME MEASURE(S): Primary outcome: identify correlates of UPF intake. SECONDARY OUTCOME: determine if UPF intake is associated with body mass index change. ANALYSIS: Adjusted ß linear regression, linear regression, P <0.05. RESULTS: Ultra-processed food accounted for 67.6% of total caloric intake. In adjusted models, children's UPF intake was positively associated with increasing child age, greater hours watching television, and more frequent parent soda/fast-food intake. Ultra-processed food intake was negatively associated with higher parent education and reported race/ethnicity other than non-Hispanic White. There was no association between UPF intake and weight. CONCLUSIONS AND IMPLICATIONS: There are several predictors of UPF intake in young children. Family-level interventions could be implemented to encourage the intake of minimally processed foods before and during preschool years.

Healthy Behaviors Among Non-Hispanic Black and Hispanic People Affected by Cancer During the Posttreatment Survivorship: A Qualitative Study.

BACKGROUND: There are disparities in health behaviors across racial and ethnic groups. However, limited studies focus on cancer survivors' experiences developing and maintaining healthy behaviors, particularly in non-Hispanic Black (NHB) and Hispanic people. OBJECTIVE: This study aimed to understand the experiences of NHB and Hispanic people affected by cancer in developing and maintaining positive health behaviors beyond a cancer diagnosis. METHODS: The data were collected in a mixed-method study through semistructured interviews with 29 NHB and Hispanic cancer survivors between June and October 2022. Conventional content analysis was used. RESULTS: The lived experiences of cancer survivors were narrated in 3 themes: impact of a cancer diagnosis on oneself, facilitators and barriers to health and health behaviors, and utilization of available sources for health. Facilitators and barriers to health and health behaviors were further explored as biological (eg, symptoms, comorbidities), behavioral (eg, help-seeking behavior, sleep pattern), physical/built (eg, available sources, neighborhood), and sociocultural environment (eg, income, transportation, knowledge, culture, upbringing, household and community composition, social and family network), and healthcare system-related factors (eg, insurance coverage, personal preferences, perceived discrimination, and stigma). CONCLUSION: Non-Hispanic Black and Hispanic people, specifically those living in disadvantaged neighborhoods with limited sources or where they feel discriminated and stereotyped, those with limited income and transportation, and those with physical, social, or mental health problems, seemed to have challenges prioritizing health behaviors and maintaining healthy living. IMPLICATIONS FOR PRACTICE: Biological, behavioral, and psychosocial determinants of health behaviors should be addressed through multilevel collaborations among different levels of partners.

New Moms Wellness Study: the randomized controlled trial study protocol for an intervention study to increase fruit and vegetable intake and lower breast cancer risk through weekly counseling and supplemental fruit and vegetable box delivery in breastfeeding women.

BACKGROUND: Laboratory studies indicate that chemicals in fruits and vegetables have anti-carcinogenic and anti-inflammatory activities that can lower breast cancer risk. However, epidemiologic studies of the association between fruit and vegetable intake and breast cancer risk have produced mixed results. Measurement error, confounding, and an emphasis on diet in later adulthood may contribute to weak associations. This paper describes a randomized controlled diet intervention trial in breastfeeding women to examine the effect of high fruit and vegetable intake on breast cancer risk factors, including weight, DNA methylation and inflammatory markers. METHODS: Eligible breastfeeding women who reside within a 35-mile radius of Amherst, MA are enrolled at five to six weeks postpartum and randomly assigned to a Fruit and Vegetable Intervention Arm (target n = 200) or to a USDA MyPlate Control Arm (target n = 200). The Fruit and Vegetable Intervention group receives weekly telephone or video-based counseling to encourage intake of at least eight to ten daily servings of fruits and vegetables and a weekly delivery of a supplemental box of fruits and vegetables for 20 weeks, and less intensive counseling for up to one year. Breastmilk and infant fecal specimens are collected at baseline, 10 and 20 weeks. Anthropometric measurements are obtained at these timepoints and at the 1-year follow-up. The primary outcomes are change in DNA methylation in breast epithelial cells and change in inflammatory markers in breastmilk from randomization to 20 weeks; and change in weight, waist circumference, and fruit and vegetable intake for the period from randomization to 20 weeks and 1 year. DISCUSSION: This 1-year randomized diet intervention trial in breastfeeding women will assess whether intake of at least eight to ten daily servings of fruits and vegetables per day improves biomarkers of breast cancer risk directly in the breast (i.e., DNA methylation and inflammatory markers) and helps women maintain a healthy weight. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04374747. Registered May 5, 2020. https://www. CLINICALTRIALS: gov/ct2/show/NCT04374747 .

Prediagnostic White Blood Cell DNA Methylation and Risk of Breast Cancer in the Prostate Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort.

BACKGROUND: White blood cell (WBC) DNA may contain methylation patterns that are associated with subsequent breast cancer risk. Using a high-throughput array and samples collected, on average, 1.3 years prior to diagnosis, a case-cohort analysis nested in the prospective Sister Study identified 250 individual CpG sites that were differentially methylated between breast cancer cases and noncases. We examined five of the top 40 CpG sites in a case-control study nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort. METHODS: We investigated the associations between prediagnostic WBC DNA methylation in 297 breast cancer cases and 297 frequency-matched controls. Two WBC DNA specimens from each participant were used: a proximate sample collected 1 to 2.9 years and a distant sample collected 4.2-7.3 years prior to diagnosis in cases or the comparable timepoints in controls. WBC DNA methylation level was measured using targeted bisulfite amplification sequencing. We used logistic regression to obtain ORs and 95% confidence intervals (CI). RESULTS: A one-unit increase in percent methylation in ERCC1 in proximate WBC DNA was associated with increased breast cancer risk (adjusted OR = 1.29; 95% CI, 1.06-1.57). However, a one-unit increase in percent methylation in ERCC1 in distant WBC DNA was inversely associated with breast cancer risk (adjusted OR = 0.83; 95% CI, 0.69-0.98). None of the other ORs met the threshold for statistical significance. CONCLUSIONS: There was no convincing pattern between percent methylation in the five CpG sites and breast cancer risk. IMPACT: The link between prediagnostic WBC DNA methylation marks and breast cancer, if any, is poorly understood.

Psychotropic Medication Use and Postmenopausal Breast Cancer Risk.

BACKGROUND: Prior studies evaluating psychotropic medications in relation to breast cancer risk are inconsistent and have not separately evaluated invasive and in situ disease. METHODS: We estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of psychotropic medication use (any, typical antipsychotics, atypical antipsychotics, and lithium) with invasive and in situ breast cancer risk among Women's Health Initiative participants (N = 155,737). RESULTS: Prevalence of psychotropic medication use was low (n = 642; 0.4%). During an average 14.8 (SD, 6.5) years of follow-up, 10,067 invasive and 2,285 in situ breast tissues were diagnosed. Any psychotropic medication use was not associated with invasive breast cancer risk compared with nonusers (HR, 0.82; 95% CI, 0.57-1.18). In situ breast cancer risk was higher among "typical" antipsychotic medication users compared with nonusers (HR, 2.05; 95% CI, 0.97-4.30). CONCLUSIONS: These findings do not support an association of psychotropic medication use with invasive breast cancer risk. The possible elevation in in situ breast cancer risk associated with "typical" antipsychotics could not be explained by differences in screening mammography utilization and merits further study. IMPACT: Our findings contribute to knowledge of the safety profile of psychotropic medications and may be useful to clinicians and patients considering use of these medications.

Urinary concentrations of phthalate biomarkers and weight change among postmenopausal women: a prospective cohort study.

BACKGROUND: Some phthalates are endocrine disrupting chemicals used as plasticizers in consumer products, and have been associated with obesity in cross-sectional studies, yet prospective evaluations of weight change are lacking. Our objective was to evaluate associations between phthalate biomarker concentrations and weight and weight change among postmenopausal women. METHODS: We performed cross-sectional (N = 997) and longitudinal analyses (N = 660) among postmenopausal Women's Health Initiative participants. We measured 13 phthalate metabolites and creatinine in spot urine samples provided at baseline. Participants' weight and height measured at in-person clinic visits at baseline, year 3, and year 6 were used to calculate body mass index (BMI). We fit multivariable multinomial logistic regression models to explore cross-sectional associations between each phthalate biomarker and baseline BMI category. We evaluated longitudinal associations between each biomarker and weight change using mixed effects linear regression models. RESULTS: In cross-sectional analyses, urinary concentrations of some biomarkers were positively associated with obesity prevalence (e.g. sum of di (2-ethylhexyl) phthalate metabolites [ΣDEHP] 4th vs 1st quartile OR = 3.29, 95% CI 1.80-6.03 [p trend< 0.001] vs normal). In longitudinal analyses, positive trends with weight gain between baseline and year 3 were observed for mono-(2-ethyl-5-oxohexyl) phthalate, monoethyl phthalate (MEP), mono-hydroxybutyl phthalate, and mono-hydroxyisobutyl phthalate (e.g. + 2.32 kg [95% CI 0.93-3.72] for 4th vs 1st quartile of MEP; p trend < 0.001). No statistically significant associations were observed between biomarkers and weight gain over 6 years. CONCLUSIONS: Certain phthalates may contribute to short-term weight gain among postmenopausal women.

Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk.

BACKGROUND: Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. METHODS: We conducted a nested case-control study within the Women's Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up. RESULTS: Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years. CONCLUSIONS: In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.

Dietary Intervention to Increase Fruit and Vegetable Consumption in Breastfeeding Women: A Pilot Randomized Trial Measuring Inflammatory Markers in Breast Milk.

BACKGROUND: Diets rich in fruits and vegetables (F/V) can reduce the inflammatory profile of circulating cytokines and potentially decrease the risk of breast cancer. However, the extent to which a diet rich in F/V alters cytokine levels in breast tissue remains largely unknown. Breast milk provides a means of assessing concentrations of secreted cytokines in the breast microenvironment and is a potential tool for studying the effects of diet on inflammation in breast tissue and breast cancer risk. OBJECTIVE: The aim of this pilot randomized trial was to test the feasibility of increasing F/V intake in breastfeeding women and of measuring changes in markers of inflammation in breast milk. DESIGN AND INTERVENTION: Participants randomized to the intervention (n=5) were provided weekly boxes of F/V, along with dietary counseling, to increase consumption of F/V to 8 to 10 daily servings for 12 consecutive weeks. Controls (n=5) were directed to the US Department of Agriculture's "ChooseMyPlate" diet for pregnancy and breastfeeding. PARTICIPANTS/SETTING: Ten breastfeeding women consuming fewer than five servings of F/V per day, as estimated by the National Institutes of Health "All-Day" Fruit and Vegetable Screener (F/V Screener), were recruited through flyers and a lactation consultant between February and May 2016 in the Western Massachusetts area. MAIN OUTCOME MEASURES: Baseline demographic and F/V intake data were collected during enrollment. At week 1 and week 13 (final) home visits, participants provided milk samples and anthropometric measurements were recorded. Participants completed F/V screeners at baseline and at study end. Adiponectin, leptin, C-reactive protein, and 11 additional cytokines were measured in breast milk collected at weeks 1 and 13. STATISTICAL ANALYSES: F/V consumption at baseline and after the final visit, and between controls and intervention groups, was compared with dependent and independent t tests, respectively. Differences between cytokine levels at weeks 1 and 13 were assessed with a mixed-effects repeated-measures model. RESULTS: All women in the intervention increased F/V intake and were consuming more servings than controls by week 13; daily serving of F/V at baseline and final visit: controls=1.6 and 2.0, diet=2.6 and 9.9. Most cytokines were detected in the majority of milk samples: 12 were detected in 90% to 100% of samples, one was detected in 75% of samples, and one was detected in 7.5% of samples; coefficients of variation were below 14% for 11 of the cytokines. CONCLUSIONS: These preliminary findings indicate that it is feasible to significantly increase F/V intake in breastfeeding women and provide support for conducting a larger diet intervention study in breastfeeding women, in which longer-term benefits of the intervention are assessed.

Association of urinary levels of 6-sulfatoxymelatonin (aMT6s) with prevalent and incident hypertension.

Laboratory studies indicate that melatonin has beneficial vascular effects. However, epidemiologic studies on the relationship between endogenous levels of melatonin and hypertension in humans are limited. We examined the association of quartile levels of 6-sulfatoxymelatonin (aMT6s) in first morning urines with prevalent and incident hypertension in 777 postmenopausal women who were originally part of a case-control study of breast cancer nested in the Women's Health Initiative Observational Study. A total of 321 prevalent and 172 incident cases of hypertension were studied. In cross-sectional analyses, higher quartile level of aMT6s was associated with lower odds of hypertension (Q4 versus Q1; odds ratio = 0.57; 95% confidence interval [CI]: 0.3-0.9), after adjustment for age, body mass index and other risk factors. We also examined the association between baseline aMT6s levels and risk of incident hypertension. Compared to women in the lowest quartile of urinary aMT6s, the multivariable-adjusted hazard ratios and 95% CIs of incident hypertension for women in the second, third and highest quartile were 1.16 (0.8-1.8), 0.96 (0.6-1.5) and 1.02 (0.6-1.6), respectively. The mean change in systolic and diastolic blood pressure over 3 years also did not vary by baseline quartile levels of aMT6s. Although we found no evidence of a prospective association between urinary levels of aMT6s and risk of incident hypertension in postmenopausal women, our cross-sectional results provide some possible evidence of a role for physiologic levels of melatonin in hypertension. Additional larger studies are warranted, preferably with a wider range of ages, both genders and multiple melatonin measurements.

Antidepressant Use and Risk of Colorectal Cancer in the Women's Health Initiative.

Background: Some prior studies have reported reduced colorectal cancer risk among individuals using antidepressant medications, especially selective serotonin reuptake inhibitors (SSRIs). Yet most studies have not considered the potential role of depression or other confounders in their analyses.Methods: We utilized prospectively collected data from 145,190 participants in the Women's Health Initiative, among whom 2,580 incident colorectal cancer cases were diagnosed. Antidepressant use and depressive symptoms were assessed at baseline and follow-up study visits. Cox proportional hazards regression models with adjustment for depressive symptoms and other covariates were utilized to estimate HRs and 95% confidence intervals (CIs) for associations between antidepressant use and colorectal cancer.Results: Antidepressant use was reported by 6.9% of participants at baseline, with SSRIs the most common class of antidepressant used. In multivariable analyses, including adjustment for depressive symptomology, we observed no statistically significant association between antidepressant use overall (HR = 0.90; 95% CI, 0.75-1.09) or with SSRIs specifically (HR = 1.08; 95% CI, 0.85-1.37) and colorectal cancer risk. A borderline significant reduction in colorectal cancer risk was observed for use of tricyclic antidepressants (HR = 0.76; 95% CI, 0.56-1.04). Severe depressive symptoms were independently associated with a 20% increased risk of colorectal cancer (HR = 1.21; 95% CI, 1.09-1.48). Results were similar for separate evaluations of colon and rectal cancer.Conclusions: We observed no evidence of an association between antidepressant use, overall or by therapeutic class, and colorectal cancer risk.Impact: These results suggest that antidepressants may not be useful as chemopreventive agents for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(8); 892-8. ©2018 AACR.

White blood cell DNA methylation and risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).

BACKGROUND: Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. METHODS: To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort. A total of 428 invasive breast cancer cases and 419 controls, frequency matched on age at entry (55-59, 60-64, 65-69, ≥70 years), year of entry (on/before September 30, 1997, on/after October 1, 1997) and period of DNA extraction (previously extracted, newly extracted) were included. The ratio of 5-methyl-2' deoxycytidine [5-mdC] to 2'-deoxyguanine [dG], assuming [dG] = [5-mdC] + [2'-deoxycytidine [dC]] (%5-mdC), was determined by liquid chromatography-electrospray ionization-tandem mass spectrometry, an especially accurate method for assessing total genomic DNA methylation. RESULTS: Odds ratio (OR) estimates and 95% confidence intervals (CI) for breast cancer risk adjusted for age at entry, year of entry, and period of DNA extraction, were 1.0 (referent), 0.89 (95% CI, 0.6-1.3), 0.88 (95% CI, 0.6-1.3), and 0.84 (95% CI, 0.6-1.2) for women in the highest compared to lowest quartile levels of %5md-C (p for trend = .39). Effects did not meaningfully vary by time elapsed from WBC collection to diagnosis. DISCUSSION: These results do not support the hypothesis that global DNA hypomethylation in WBC DNA is associated with increased breast cancer risk prior to the appearance of clinical disease.

Relationships between Global DNA Methylation in Circulating White Blood Cells and Breast Cancer Risk Factors.

It is not yet clear whether white blood cell DNA global methylation is associated with breast cancer risk. In this review we examine the relationships between multiple breast cancer risk factors and three markers of global DNA methylation: LINE-1, 5-mdC, and Alu. A literature search was conducted using Pubmed up to April 1, 2016, using combinations of relevant outcomes such as "WBC methylation," "blood methylation," "blood LINE-1 methylation," and a comprehensive list of known and suspected breast cancer risk factors. Overall, the vast majority of reports in the literature have focused on LINE-1. There was reasonably consistent evidence across the studies examined that males have higher levels of LINE-1 methylation in WBC DNA than females. None of the other demographic, lifestyle, dietary, or health condition risk factors were consistently associated with LINE-1 DNA methylation across studies. With the possible exception of sex, there was also little evidence that the wide range of breast cancer risk factors we examined were associated with either of the other two global DNA methylation markers: 5-mdC and Alu. One possible implication of the observed lack of association between global WBC DNA methylation and known breast cancer risk factors is that the association between global WBC DNA methylation and breast cancer, if it exists, is due to a disease effect.

Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women's Health Across the Nation.

PURPOSE: Two case-control studies reported a 50 % decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS), but one cohort study found no association. VMS may be triggered by declining estrogen levels during menopause, whereas elevated estrogen levels have been associated with increased breast cancer risk. VMS may thus be indicative of lower susceptibility to breast cancer. METHODS: We evaluated this relationship in the longitudinal Study of Women's Health Across the Nation (SWAN), using discrete survival analysis of approximately annual data on VMS and self-reported breast cancer occurrences for up to 13 years of follow-up in 3,098 women who were pre- or early perimenopausal at enrollment. RESULTS: Over an average 11.4 years of follow-up, 129 incident breast cancer cases were self-reported, and approximately 50 % of participants experienced VMS. Symptomatic women had a reduced risk of breast cancer compared to non-symptomatic women (adjusted HR 0.63, 95 % CI 0.39, 1.00). The association was stronger in the subgroup of women who fully transitioned to postmenopause during follow-up (n = 67 cases, adjusted HR 0.45, 95 % CI 0.26, 0.77). CONCLUSION: VMS appeared to be a marker of reduced breast cancer risk. Future research is needed to understand the biology underlying this relationship.

Urinary levels of phthalate metabolites and cardiovascular disease mortality (NHANES, 1999-2008).

BACKGROUND: Mechanistic data and results from a limited number of cross-sectional epidemiologic studies have suggested a possible link between phthalates and adverse cardiovascular outcomes. OBJECTIVE: To evaluate the association between urinary levels of eight phthalate metabolites and subsequent risk of cardiovascular death in a prospective cohort analysis. METHODS: We identified 5080 individuals 40 years or older who participated in the continuous National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008 and who had measured phthalate levels available. We a priori excluded individuals in later cycles of NHANES with measured phthalates so as to have the potential of at least three years of follow-up time on all members of the cohort. Questionnaire, exam and laboratory data were merged with a public access NHANES mortality file updated through December 31, 2011. The associations between cardiovascular death and quartile levels of the phthalate metabolites were investigated using Cox proportional hazard models. RESULTS: There were 175 deaths due to cardiovascular disease deaths over a mean of 7.0 years of follow-up. No association between cardiovascular disease mortality and individual urinary phthalate metabolites was observed. After adjustments, hazard ratios comparing the highest to lowest quartile ranged from 0.73 (95%CI: 0.5-1.2) for mono-ethyl phthalate [MEP] to 1.4 (95%CI:0.8-2.5) for mono-(2-ethyl-5-hydroxyhexyl) phthalate [MEHHP]. CONCLUSIONS: Urinary levels of phthalate metabolites were not associated with increased cardiovascular disease mortality. Additional larger cohort studies with longer follow-up focused on cardiovascular disease incidence are needed.

Impact of incident diabetes on atherosclerotic cardiovascular disease according to statin use history among postmenopausal women.

To compare impact of incident diabetes on atherosclerotic cardiovascular disease (ASCVD) risk among postmenopausal women according to statin use. Prospective data from 120,499 postmenopausal women without prevalent diabetes or cardiovascular disease at baseline from the Women's Health Initiative were used. Incident diabetes was self-reported annually and defined as treatment with pills or injectable medication for diabetes. Current statin use was determined at enrollment and years 1, 3, 6, 9 and 13.5 in the three clinical trial arms, and at baseline, year 3, and 13.5 for the observational study. The primary outcome was incident ASCVD events, self-reported annually and adjudicated by blinded local and central physicians. Incident diabetes and statin use status were fitted as time-varying covariates in Cox regression models to assess ASCVD risk during an average follow-up of 13.6 years. For those not on statins at the time of diabetes diagnosis, there was a 42 % increased risk of ASCVD [hazard ratio (HR) 1.42, 95 % CI 1.28-1.58] among women with incident diabetes versus those without diabetes. Among women on statins, there was a 39 % increased risk of ASCVD (HR 1.39, 95 % CI 1.12-1.74) in women with incident diabetes versus those without diabetes. The increased ASCVD risk due to diabetes was similar between women before or after initiating statins (P = 0.89). Whether diabetes was diagnosed before or after statin use did not alter the increased risk of ASCVD associated with diabetes. Mitigating the increased incidence of diabetes in statin users could increase the ASCVD benefit-to-risk ratio of statins.

Effects of Pomegranate Juice on Hormonal Biomarkers of Breast Cancer Risk.

Pomegranate is a rich source of polyphenols. Laboratory studies suggest polyphenols may exert breast cancer preventive effects through modulation of endogenous sex hormone levels. The aim of this study was to determine the effect of pomegranate juice consumption on serum levels of estradiol, estrone, testosterone, androstenedione, and sex hormone binding globulin (SHBG). Sixty-four healthy postmenopausal women were randomly assigned to drink 8 ounces of either 100% commercial pomegranate juice (intervention) or apple juice (control) for 3 weeks. Overall, women in the intervention group did not experience any significant decline in serum sex hormones or SHBG compared to women in the control group. In subgroup analyses restricted to 38 normal weight women, women in the intervention group compared to control group had a significant decline in estrone (pg/mL) and testosterone levels (pg/mL): pomegranate: -61.6 [95% confidence interval (CI): -175.8 to 52.6), apple: 1.1 (95% CI: -5.4 to 7.7), P = 0.05, and pomegranate: -289.1 (95% CI: -630.7 to 52.5), apple: 79.6 (95% CI: -77.8 to 236.9), P = 0.03, respectively. Because of several study limitations, results should be considered preliminary. Additional larger trials would be needed to determine effects in normal versus overweight/obese women.

The effect of change in body mass index on volumetric measures of mammographic density.

BACKGROUND: Understanding how changes in body mass index (BMI) relate to changes in mammographic density is necessary to evaluate adjustment for BMI gain/loss in studies of change in density and breast cancer risk. Increase in BMI has been associated with a decrease in percent density, but the effect on change in absolute dense area or volume is unclear. METHODS: We examined the association between change in BMI and change in volumetric breast density among 24,556 women in the San Francisco Mammography Registry from 2007 to 2013. Height and weight were self-reported at the time of mammography. Breast density was assessed using single x-ray absorptiometry measurements. Cross-sectional and longitudinal associations between BMI and dense volume (DV), non-dense volume (NDV), and percent dense volume (PDV) were assessed using multivariable linear regression models, adjusted for demographics, risk factors, and reproductive history. RESULTS: In cross-sectional analysis, BMI was positively associated with DV [ß, 2.95 cm(3); 95% confidence interval (CI), 2.69-3.21] and inversely associated with PDV (ß, -2.03%; 95% CI, -2.09, -1.98). In contrast, increasing BMI was longitudinally associated with a decrease in both DV (ß, -1.01 cm(3); 95% CI, -1.59, -0.42) and PDV (ß, -1.17%; 95% CI, -1.31, -1.04). These findings were consistent for both pre- and postmenopausal women. CONCLUSION: Our findings support an inverse association between change in BMI and change in PDV. The association between increasing BMI and decreasing DV requires confirmation. IMPACT: Longitudinal studies of PDV and breast cancer risk, or those using PDV as an indicator of breast cancer risk, should evaluate adjustment for change in BMI.