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Breast cancer risk reduction strategies have been well-validated, but barriers remain for high-risk individuals to adopt them. We performed a study among participants with high risk of breast cancer to validate whether a virtual breast health decision tool impacted a participants willingness to start risk-reducing activities, identify barriers to adopting these strategies, and understand if it affects breast cancer anxiety. The study sample was 318 participants in the personalized (investigational) arm of the Women Informed to Screen Depending on Measures of risk (WISDOM) clinical trial. After reviewing the tool, these participants completed a feedback survey. We demonstrated that 15 (4.7%) women were taking endocrine risk reduction, 123 (38.7%) were reducing alcohol intake, and 199 (62.6%) were exercising. In the three-month follow-up survey of 109 respondents, only 8 of 61 (13.1%) women who considered endocrine risk reduction pursued it. In contrast, 11 of 16 (68%) participants who considered alcohol reduction pursued the activity, and 14 of 24 (58%) women who considered exercise followed through. Participants listed fear of side effects as the most common barrier to endocrine risk reduction. We also present further steps to be taken to improve the effectiveness of the Breast Health Decisions tool.

BackgroundBreast density is an important risk factor for breast cancer and is known to be associated with characteristics such as age, race, and hormone levels; however, it is unclear what factors contribute to changes in breast density in postmenopausal women over time. Understanding factors associated with density changes may enable a better understanding of breast cancer risk and facilitate potential strategies for prevention.MethodsThis study investigated potential associations between personal factors and changes in mammographic density in a cohort of 3,392 postmenopausal women with no personal history of breast cancer between 2011 and 2017. Self-reported information on demographics, breast and reproductive history, and lifestyle factors, including body mass index (BMI), alcohol intake, smoking, and physical activity, was collected by an electronic intake form, and breast imaging reporting and database system (BI-RADS) mammographic density scores were obtained from electronic medical records. Factors associated with a longitudinal increase or decrease in mammographic density were identified using Fisher's exact test and multivariate conditional logistic regression.Results7.9% of women exhibited a longitudinal decrease in mammographic density, 6.7% exhibited an increase, and 85.4% exhibited no change. Longitudinal changes in mammographic density were correlated with age, race/ethnicity, and age at menopause in the univariate analysis. In the multivariate analysis, Asian women were more likely to exhibit a longitudinal increase in mammographic density and less likely to exhibit a decrease compared to White women. On the other hand, obese women were less likely to exhibit an increase and more likely to exhibit a decrease compared to normal weight women. Women who underwent menopause at age 55 years or older were less likely to exhibit a decrease in mammographic density compared to women who underwent menopause at a younger age. Besides obesity, lifestyle factors (alcohol intake, smoking, and physical activity) were not associated with longitudinal changes in mammographic density.ConclusionsThe associations we observed between Asian race/obesity and longitudinal changes in BI-RADS density in postmenopausal women are paradoxical in that breast cancer risk is lower in Asian women and higher in obese women. However, the association between later age at menopause and a decreased likelihood of decreasing in BI-RADS density over time is consistent with later age at menopause being a risk factor for breast cancer and suggests a potential relationship between greater cumulative lifetime estrogen exposure and relative stability in breast density after menopause. Our findings support the complexity of the relationships between breast density, BMI, hormone exposure, and breast cancer risk.

Animal and epidemiologic studies suggest that there may be adverse health effects from exposure to glyphosate, the most highly used pesticide in the world, and its metabolite aminomethylphosphonic acid (AMPA). Meanwhile, consumption of organic foods (presumably grown free of chemical pesticides) has increased in recent years. However, there have been limited biomonitoring studies assessing the levels of human glyphosate and AMPA exposure in the United States. We examined urinary levels of glyphosate and AMPA in the context of organic eating behavior in a cohort of healthy postmenopausal women residing in Southern California and evaluated associations with demographics, dietary intake, and other lifestyle factors. 338 women provided two first-morning urine samples and at least one paired 24-h dietary recall reporting the previous day's dietary intake. Urinary glyphosate and AMPA were measured using LC-MS/MS. Participants reported on demographic and lifestyle factors via questionnaires. Potential associations were examined between these factors and urinary glyphosate and AMPA concentrations. Glyphosate was detected in 89.9% of urine samples and AMPA in 67.2%. 37.9% of study participants reported often or always eating organic food, 30.2% sometimes, and 32.0% seldom or never. Frequency of organic food consumption was associated with several demographic and lifestyle factors. Frequent organic eaters had significantly lower urinary glyphosate and AMPA levels, but not after adjustment for covariates. Grain consumption was significantly associated with higher urinary glyphosate levels, even among women who reported often or always eating organic grains. Soy protein and alcohol consumption as well as high frequency of eating fast food were associated with higher urinary AMPA levels. In conclusion, in the largest study to date examining paired dietary recall data and measurements of first-void urinary glyphosate and AMPA, the vast majority of subjects sampled had detectable levels, and significant dietary sources in the American diet were identified.

BackgroundAltered DNA methylation may be an intermediate phenotype between breast cancer risk factors and disease. Mammographic density is a strong risk factor for breast cancer. However, no studies to date have identified an epigenetic signature of mammographic density. We performed an epigenome-wide association study of mammographic density.MethodsWhite blood cell DNA methylation was measured for 385 postmenopausal women using the Illumina Infinium MethylationEPIC BeadChip array. Differential methylation was assessed using genome-wide, probe-level, and regional analyses. We implemented a resampling-based approach to improve the stability of our findings.ResultsOn average, women with elevated mammographic density exhibited DNA hypermethylation within CpG islands and gene promoters compared to women with lower mammographic density. We identified 250 CpG sites for which DNA methylation was significantly associated with mammographic density. The top sites were located within genes associated with cancer, including HDLBP, TGFB2, CCT4, and PAX8, and were more likely to be located in regulatory regions of the genome. We also identified differential DNA methylation in 37 regions, including within the promoters of PAX8 and PF4, a gene involved in the regulation of angiogenesis. Overall, our results paint a picture of epigenetic dysregulation associated with mammographic density.ConclusionMammographic density is associated with differential DNA methylation throughout the genome, including within genes associated with cancer. Our results suggest the potential involvement of several genes in the biological mechanisms behind differences in breast density between women. Further studies are warranted to explore these potential mechanisms and potential links to breast cancer risk.

BackgroundGlyphosate is the most commonly used herbicide in the world and is purported to have a variety of health effects, including endocrine disruption and an elevated risk of several types of cancer. Blood DNA methylation has been shown to be associated with many other environmental exposures, but to our knowledge, no studies to date have examined the association between blood DNA methylation and glyphosate exposure.ObjectiveWe conducted an epigenome-wide association study to identify DNA methylation loci associated with urinary glyphosate and its metabolite aminomethylphosphonic acid (AMPA) levels. Secondary goals were to determine the association of epigenetic age acceleration with glyphosate and AMPA and develop blood DNA methylation indices to predict urinary glyphosate and AMPA levels.MethodsFor 392 postmenopausal women, white blood cell DNA methylation was measured using the Illumina Infinium MethylationEPIC BeadChip array. Glyphosate and AMPA were measured in two urine samples per participant using liquid chromatography-tandem mass spectrometry. Methylation differences at the probe and regional level associated with glyphosate and AMPA levels were assessed using a resampling-based approach. Probes and regions that had an false discovery rate q

Breast cancer risk reduction has been validated by large-scale clinical trials, but uptake remains low. A risk communication tool could provide personalized risk-reduction information for high-risk women. A low-literacy-friendly, visual, and personalized tool was designed as part of the Women Informed to Screen Depending On Measures of risk (WISDOM) study. The tool integrates genetic, polygenic, and lifestyle factors, and quantifies the risk-reduction from undertaking medication and lifestyle interventions. The development and design process utilized feedback from clinicians, decision-making scientists, software engineers, and patient advocates. We piloted the tool with 17 study participants, collecting quantitative and qualitative feedback. Overall, participants felt they better understood their personalized breast cancer risk, were motivated to reduce their risk, and considered lifestyle interventions. The tool will be used to evaluate whether risk-based screening leads to more informed decisions and higher uptake of risk-reduction interventions among those most likely to benefit.

BackgroundTo identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups.MethodsData was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin. Using genotyped and imputed data from Illumina's Multiethnic array, we conducted genome-wide association analyses with linear mixed models for all ethnicities, except for the smaller Japanese-American group, where we used additive genetic models with gene-dropping.ResultsFindings included ethnic-specific genetic associations and heterogeneity across ethnicities. Most significant associations were outside our candidate linkage regions and were coincident within a gene or intergenic region, with two exceptions in European-American families: (a) within previously identified linkage region on chromosome 2, two significant GLI2-TFCP2L1 associations with weight, and (b) one chromosome 11 variant near CADM1-LINC00900 with pleiotropic blood pressure effects.ConclusionsThis multiethnic family study found genetic heterogeneity and coincident associations (with one case of pleiotropy), highlighting the importance of including diverse populations in genetic research and illustrating the complex genetic architecture underlying MetS.

ObjectiveAlcohol intake is a known risk factor for breast cancer. National organizations recommend that women consume no more than one serving of alcohol per day, if at all; however, many women exceed this recommendation, and some are unwilling to decrease consumption. Our study sought to identify factors associated with women's unwillingness to decrease their alcohol intake to decrease their breast cancer risk.Methods942 women in a screening mammography cohort were asked questions about their demographics, personal and family health history, lifestyle factors, and willingness/unwillingness to decrease alcohol intake to decrease their breast cancer risk. Univariate and multivariate analyzes of their responses were performed.Results13.2% of women in our cohort indicated they were unwilling to decrease their alcohol intake to reduce their breast cancer risk. After adjusting for potential confounders, women who were 60 years and older were more than twice as unwilling to decrease their alcohol intake compared to their younger counterparts (P = .0002). Women who had an annual household income of more than $200,000 were 1.75 times more unwilling to decrease their alcohol intake compared to their less affluent counterparts (P = .033). Unwillingness was not significantly associated with race/ethnicity, education, having a first-degree family member with cancer, health perception, breast cancer risk perception, or BMI.ConclusionsLevels of unwillingness to decrease alcohol intake differed by age and household income. An opportunity is present to potentially decrease breast cancer risk in the community by educating women, especially older and more affluent women, about alcohol as a risk factor for breast cancer and the importance of limiting one's alcohol intake.

Environmental factors have been linked to many diseases and health conditions, but reliable assessment of environmental exposures is challenging. Developing biomarkers of environmental exposures, rather than relying on self-report, will improve our ability to assess the association of such exposures with disease. Epigenetic markers, most notably DNA methylation, have been identified for some environmental exposures, but identification of markers for additional exposures is still needed. The rationale behind the Markers for Environmental Exposures (MEE) Study was to (1) identify biomarkers, especially epigenetic markers, of environmental exposures, such as pesticides, air/food/water contaminants, and industrial chemicals that are commonly encountered in the general population; and (2) support the study of potential relationships between environmental exposures and health and health-related factors. The MEE Study is a cross-sectional study with potential for record linkage and follow-up. The well-characterized cohort of 400 postmenopausal women has generated a repository of biospecimens, including blood, urine, and saliva samples. Paired data include an environmental exposures questionnaire, a breast health questionnaire, dietary recalls, and a food frequency questionnaire. This work describes the rationale, study design, and cohort characteristics of the MEE Study. In addition to our primary research goals, we hope that the data and biorepository generated by this study will serve as a resource for future studies and collaboration.

BackgroundThis study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models.ResultsAfter adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21).ConclusionsTo our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies.

Abstract: Background: WISDOM is a 100,000 healthy women preference-tolerant, pragmatic study comparing traditional annual screening to personalized risk-based breast screening. The novelty of WISDOM personalized screening is the integration of previously validated genetic and clinical risk factors (age, family history, breast biopsy results, ethnicity, mammographic density) into a single risk assessment model that directs the starting age, timing, and frequency of screening. The goal of WISDOM is to determine if personalized screening, compared to annual screening, is as safe, less morbid, enables prevention, and is more accepted by women. The study is registered on ClinicalTrials.gov, NCT02620852. Methods: Women aged 40-74 years with no history of breast cancer or DCIS, and no previous double mastectomy can join the study online at wisdomstudy.org. Participants can either elect randomization or self-select a study arm. Then, they can provide electronic consent and sign the Release for Medical Information via DocuSign. For all participants, 5-year risk of developing breast cancer is calculated according to the Breast Cancer Screening Consortium (BCSC) model. Participants in the personalized arm undergo panel-based mutation testing (BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, ATM, PALB2, and CHEK2), and their 5-year risk is calculated using the BCSC score combined with a Polygenic Risk Score (BCSC-PRS) that includes 75 single nucleotide polymorphisms (SNPs) known to increase breast cancer risk (will increase to 229). The SNPs and mutations are assessed by saliva-based testing through Color Genomics. 5-year risk level thresholds are used to stratify for low-, moderate- and high risk. Risk stratification determines age to start, stop, and frequency of screening. Accrual: As of July 2019, the WISDOM study is open to all eligible women in California, North Dakota, South Dakota, Minnesota, Iowa, Illinois, and New Jersey. To date, 30,392 eligible women have registered, and 21,392 women have consented to participate in the trial. The median age was 56 years. 85% of participants were Caucasian, 2% African-American, and 5% Asian. 6% self-reported Hispanic ethnicity. WISDOM is actively partnering with Blue Cross Blue Shield Association for national coverage, self-insured companies (Salesforce, Genentech, Qualcomm, CalPERS) and Medi-Cal (Inland Empire Health Plan) using a coverage with evidence progression approach. Accrual expansion and diversity: To strengthen generalizability, the WISDOM Study is enhancing the diversity of our potential participant population by expanding to other states (Alabama, Louisiana), and partnering with other health insurers and self-insured companies. Future expansion regions include Texas, Florida, South Carolina, Oklahoma, Montana, and New Mexico. Additionally, we have translated the whole study experience to Spanish to further reach Spanish-speaking communities. With the engagement of patient advocates and community partnerships, expanding diversity recruitment will strengthen our scientific knowledge of breast cancer risk and increase access to personalized breast cancer screening recommendations for all women. WISDOM enrollment will continue through 2020. Conclusions: Results at 5 years will enable us to demonstrate that personalized screening improves healthcare value by reducing screen volumes and costs without jeopardizing outcomes. Citation Format: Mandy Che, Allison Stover Fiscallini, Irene Acerbi, Yiweh Shieh, Lisa Madlensky, Jeffrey Tice, Elad Ziv, Martin Eklund, Amie Blanco, Barry Tong, Deborah Goodman, Lamees Nassereddine, Nancy Anderson, Heather Harvey, Steele Fors, Hannah L Park, Antonia Petruse, Skye Stewart, Janet Wernisch, Larissa Risty, Ian Hurley, Barbara Koenig, Celia Kaplan, Robert Hiatt, Neil Wenger, Vivian Lee, Diane Heditsian, Susie Brain, Leah Sabacan, Barbara Parker, Alexander Borowsky, Hoda Anton-Culver, Hoda Anton-Culver, Arash Naeim, Andrea Kaster, Melinda Talley, Laura van't Veer, Andrea LaCroix, Olufunmilayo I Olopade, Deepa Sheth, WISDOM Study and Athena Breast Health Network Investigators and Advocate Partners and Laura Esserman. Personalized breast cancer screening in a population-based study: Women informed to screen depending on measures of risk (WISDOM) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-03-02.

Observational genome-wide association studies require large sample sizes. Evaluating the interplay between genomic, environmental, and lifestyle factors can require even larger sample sizes. The All of Us Research Program will recruit 1 million participants to facilitate research on genomic, environmental, and lifestyle factors. Integrating participant preferences into the research process is a new paradigm and a necessary component of the All of Us Research Program. The purpose of the study is to summarize quantitative studies of participant preferences related to participation in observational genomic research studies, starting with consent through return of results. Integrating this information into the conduct of genomic studies may benefit participants, and improve participant satisfaction, recruitment, and retention. We conducted a systematic review of the literature regarding participant views related to reconsent and broad consent, use of de-identified data, contribution of data to a biorepository, risk of identification, return of individual genetic results, and motivation for participation in genomic studies. Twenty-three articles met our inclusion and exclusion criteria. Study results found that most participants support broad consent; however, significant differences related to reconsent preferences have been shown by gender and age. Most participants support the return of individual genomic results and do not feel it is necessary to maintain a link to their de-identified data. Reasons given for joining research studies varied by population source. These findings, in addition to the knowledge that participants are more accepting of broad informed consent methods when the rationale is explained, can assist in developing guidelines for future observational genomic research.

Data sharing of large genomic databases and biorepositories provides researchers adequately powered samples to advance the goals of precision medicine. Data sharing may also introduce, however, participant privacy concerns including possible reidentification. This study compares views of research participants, genetic researchers, and institutional review board (IRB) professionals regarding concerns about the use of de-identified data. An online survey was completed by cancer patients, their relatives, and controls from the Northwest Cancer Genetics Registry (n = 450) querying views about potential harms with the use of de-identified data. This was compared to our previous online national survey of human genetic researchers (n = 351) and IRB professionals (n = 208). Researchers were less likely to feel that participants would be personally identified or harmed from a study involving de-identified data or feel that a federal agency might compel researchers to disclose information about research participants. Compared to genetic researchers, IRB professionals and participants were significantly more likely to express that personal identification or harm was likely or that researchers might be forced to disclose information by a federal agency. An understanding of the differences in views regarding possible harm from the use of de-identified data between these three important stakeholder groups is necessary to move forward with genomic research.

ObjectivesGenomic information will increasingly be used to aid in the prevention, diagnosis, and treatment of disease. Several national initiatives are paving the way for this new reality, while also promoting new models of participant-engaged research. We compare the opinions of research participants in a cancer registry, human genetic researchers, and institutional review board (IRB) professionals about the return of individual-level genetic results (ROR).MethodsOnline surveys were administered to participants in a cancer registry (n = 450) and overlapping questions were compared to our previous online national surveys of human genetic researchers (n = 351) and IRB professionals (n = 208).ResultsThe majority of respondents agreed that researchers have an obligation to return individual results when they would affect a participant's health. While 77% of registry participants favored ROR if the researcher feels the participant might be interested in the results, only 30% of the IRB professionals and 25% of the genetic researchers agreed with this statement.ConclusionsSignificant differences emerged between the stakeholder groups in several ROR scenarios. Policies that are acceptable to participants, researchers and IRBs, and that ensure human subject protections and facilitate research are needed.

Combining datasets into larger and separate datasets is becoming increasingly common, and personal identifiers are often removed in order to maintain participant anonymity. Views of research participants on the use of de-identified data in large research datasets are important for future projects, such as the Precision Medicine Initiative and Cancer Moonshot Initiative. This quantitative study set in the USA examines participant preferences and evaluates differences by demographics and cancer history. Study participants were recruited from the Northwest Cancer Genetics Registry and included cancer patients, their relatives, and controls. A secure online survey was administered to 450 participants. While the majority participants were not concerned about personal identification when participating in a genetic study using de-identified data, they expressed their concern that researchers protect their privacy and information. Most participants expressed a desire that their data should be available for as many research studies as possible, and in doing so, they would increase their chance of receiving personal health information. About 20% of participants felt that a link should not be maintained between the participant and their de-identified data. Reasons to maintain a link included an ability to return individual health results and an ability to support further research. Knowledge of participants' attitudes regarding the use of data into a research repository and the maintenance of a link to de-identified data is critical to the success of recruitment into future genomic research projects.

BackgroundWith the arrival of large-scale population-based genomic research studies, such as the Precision Medicine Initiative (PMI), the question of how to best consent participants is significant, and in an era of patient-centered research, few studies have evaluated participants' preferences about re-consent and broad consent. Using quantitative methods, this study evaluates participants' views regarding the acceptability of re-consent and broad consent in subjects from the Participant Issues Project.MethodsA total of 450 participants were recruited from a cancer genetics registry, including cancer patients, their relatives, and controls. Participants completed a secure online survey.ResultsMost participants endorsed re-consent when investigating an unrelated health condition or sharing their de-identified data with an investigator at a different institution. Notification rather than re-consent was preferred when studying a different gene but the same disease. Over 80% of respondents endorsed re-consent when parents of a child gave the original consent and the child has now reached adulthood. Preferences for some scenarios varied by history of cancer at baseline, gender, stage of cancer, or case versus control group. The large majority of participants preferred the option to select broad consent categories of research.ConclusionUnderstanding research participants' preferences, including their views on the need for re-consent, are critical to the success of the PMI.

BackgroundThe practice of biorepository-based genetics research raises questions related to what ethical obligations researchers have to their participants. It is important to explore and include the thoughts of current biorepository participants as we move forward with this type of research.MethodsThirty participants (17 cancer patients, 7 cancer-free controls, and 6 relatives) were drawn from the Northwest Cancer Genetics Registry and participated in qualitative interviews lasting between 45 and 90 min. Topics explored in this study include which types of genetic test results participants of large biorepositories expect and would like to receive from research analyzing their samples, as well as thoughts on best practice for conducting this type of research.ResultsCancer cases, controls, and first-degree relatives have differing views on what results they would like to receive from biorepository-based research. Participants across all groups attempted to balance the costs and benefits of returning individual research results.DiscussionIn the wake of precision medicine, it is important to describe the range of ways participants in large biorepositories both think and talk about the utilization of their specimens for genetics research.

The integration of risk assessment into clinical breast screening holds promise in decreasing breast cancer morbidity and mortality and increasing health care efficiency. Currently, clinical recommendations regarding risk counseling, screening, and chemoprevention are being made based on a woman’s personal risk. One of the criteria that can be used to categorize a woman as “increased risk” is her projected 5-year risk for invasive breast cancer as determined by one of various risk models which are heavily based on family history. We hypothesized that the frequency of screening mammography patients at our medical institution who would be considered at “increased risk” would be different according to different risk models and according to race/ethnicity, thus impacting the volume of patients who are targeted for risk-reducing intervention. Risk scores were calculated for 307 White, Hispanic, and Asian screening mammography patients according to the Gail, BCSC, and Tyrer-Cuzick models. Scores were compared within and between race/ethnicities, according to the different models, individually and in combination. As expected, White women had higher risk scores than Hispanic and Asian women according to all models tested (p

ObjectivesTo evaluate the association between childhood physical activity and incident cardiovascular disease (CVD) during postmenopausal years.MethodsProportional hazards and logistic regression were used describe the association between self-reported childhood physical activity and CVD incidence and mortality in 36,741 postmenopausal women.ResultsOlder women, African-Americans, or nondrinkers or past drinkers self-reported the highest levels of youth physical activity and women with a history of diabetes, hypertension, overweight or obesity, or current smoking reported the highest youth physical activity dose. Youth physical activity was not associated with CVD incidence (HR=1.11; 0.93, 1.34) or mortality (HR=1.2; 0.9, 1.73).ConclusionsSelf-reported youth activity was not associated with postmenopausal CVD incidence or mortality.

Abstract: The USPSTF recommends that women who are at increased risk for breast cancer and at low risk for adverse medication effects should be offered risk-reducing medications, such as tamoxifen or raloxifene, by their clinicians. The NCCN also recommends risk counseling for women with a 5-year risk of ≥1.7% as calculated by the NCI-developed Breast Cancer Risk Assessment Tool (BCRAT, based on the Gail model) or other risk model. The integration of risk assessment into clinical breast screening holds promise in reducing breast cancer risk for many women; however, the criteria that contribute to elevated risk status are different according to different risk models. The University of California, Irvine (UCI) Athena Breast Health Network has integrated a computerized risk assessment largely based on the BCRAT into the screening mammography process at UCI mammography centers. Women identified to be at elevated risk are provided with personalized risk counseling by a Breast Health Specialist. In recent years, breast density has been increasingly recognized as a risk factor for breast cancer; however, it is not part of the BCRAT. In this pilot analysis, we sought to determine if incorporating breast density into the risk assessment program would affect the % of women in our cohort who have a 5-year risk of ≥1.7%. We hypothesized that an increased % of Asian women would reach this threshold since breast density is known to be higher in Asians. We used the BCSC model, which includes density as a variable, to calculate risk scores for a subset of our screening population (n=309), age-matched for three race/ethnic groups, and compared them to their scores according to the BCRAT. Our results showed that while Asians did exhibit significantly higher breast density (30.3% had BIRADS breast density classification 4, extremely dense) than White and Hispanic women (8.7% and 5.6%, respectively), their BCRAT and BCSC scores were significantly lower than in White women but higher than in Hispanic women, with 14.1% of Asians having a BCSC score ≥1.7% compared to 43.7% of Whites and 10.3% in Hispanics, and 17.2% of Asians having a BCRAT score of ≥1.7% compared to 34.0% of Whites and 6.5% of Hispanics. Interestingly, when differences were explored between BCRAT and BCSC scores within the same sub-group of women, the scores were not statistically different among White or Hispanic women but were approaching statistical significance in Asian women. Contrary to our hypothesis, in Asian women, BCSC-calculated risk was actually lower than according to the BCRAT. These findings suggest that, despite higher breast density, Asian women still exhibit lower breast cancer risk scores than White women; thus, a smaller proportion of Asian women in our cohort will be recommended for high risk counseling and chemoprevention. Citation Format: Hannah Lui Park, Stephanie M. Tran, Jennifer Lee, Deborah Goodman, Argyrios Ziogas, Richard Kelly, Kathryn M. Larsen, Andrea Alvarez, Chris Tannous, Julie Strope, Wendy Lynch, Hoda Anton-Culver. A pilot study comparing breast cancer risk scores using models with and without breast density among women of different race/ethnicities undergoing breast screening in the University of California, Irvine Athena Breast Health Network cohort. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3243. doi:10.1158/1538-7445.AM2014-3243

Fetal alcohol spectrum disorder (FASD) is a prevalent neurodevelopmental disability with significant implications for learning and behaviour. International research suggests that the prevalence of FASD in school-aged children is 2.3-6.3%. In this paper, we address the questions: (1) what is FASD; (2) what is the prevalence of FASD in schools; (3) what is the impact of FASD; and (4) why develop special FASD education strategies and programmes? We summarise the 18-year history of Winnipeg School Division's development of its FASD Programme of services, describe the specialised FASD classrooms and then present the results from a consensus-generating workshop comprised of 36 FASD education professionals, with over 209 years of collective FASD education programme experience, who were asked to identify and reach consensus on best strategies and lessons learned in FASD education programmes. We then suggest that effectively educating children with FASD is critical to get right if positive educational outcomes are to be realised.

BackgroundEvidence suggests that childhood physical activity may play a role in the etiology and prevention of adult chronic diseases. Because researchers must often depend on self-recalled physical activity data many years after the exposure, it is important to understand factors which may influence adult recall of childhood physical activity. This study evaluated the influence of adult characteristics on reported childhood physical activity and the association between adult physical activity and self-recalled childhood physical activity.Methods48,066 post-menopausal women from the Women's Health Initiative Observational Study reported their physical activity level during ages 5 - 9, 10 - 14, and 15 - 19.ResultsIn this cohort, over 65% of the population reported the same category of physical activity over the three childhood age groups. While higher levels of childhood physical activity were significantly associated with higher adult physical activity, this association varied by race/ethnicity, education, smoking, body mass index, history of diabetes or cardiovascular disease, social support and physical functional status. Women who were consistently highly active reported adult physical activity levels that were 2.82 MET-hr/week (95% C.I. = 2.43, 3.20) higher compared to women who were always physically inactive during childhood.ConclusionsIt is important for researchers to understand the influence of adult characteristics on reported childhood physical activity.

Objective: Metabolic syndrome (MetS) is defined by clustering of cardiometabolic components, which may be present in different combinations. The authors evaluated clustering in individuals and extended families within and across ancestry groups. Methods: The prevalence of different combinations of MetS components (high fasting glucose, low high‐density lipoprotein cholesterol, high triglycerides, high blood pressure, and abdominal obesity) was estimated in 1651 individuals (340 families) self‐reporting as European American (EA), Hispanic/Mexican American (MA), African American (AA), and Japanese American (JA). Odds ratios were estimated using logistic regression with generalized estimating equations comparing individual MetS components, number, and combinations of components for each ancestry group versus EA. Results: Clustering of all five components (Combination #16) was more prevalent in EA (29.9%) and MA (25.2%) individuals than in AA (18.7%) and JA (15.5%) individuals. Compared with EA individuals, AA individuals were 64% and 66% less likely to have high triglycerides and low high‐density lipoprotein cholesterol, whereas JA individuals were 85% and 56% less likely to have abdominal obesity and high blood pressure, respectively. Compared with EA individuals, the odds of having two, four, or five components were at least 77% lower in JA individuals, whereas the odds of having three, four, or five components were at least 3.79 times greater in MA individuals. Conclusions: Understanding heterogeneity in MetS clustering may identify factors important in reducing health disparities. [ABSTRACT FROM AUTHOR]

To enhance strengths-based service, a large urban child welfare agency in Ontario, Canada implemented part of the Signs of Safety (SOS) model in 2010. SOS was created to engage families involved with the child welfare system, and is rooted in the beliefs of collaboration, strengths-based practice, and safety. The hybrid of the full SOS model focused on the mapping conference, where cases that have been previously opened four or more times to child welfare are brought forward and discussed in a methodological fashion. Repeat referrals to child welfare agencies have dramatically increased over recent years and extant literature lacks a solid understanding of cases that have been opened on multiple occasions. Thus, the goals of mapping conferences were to reduce the total number and increase the understanding of re-opened cases, while still ensuring child safety and improving clinical service. The mapping conference includes a prescribed clinical, strength-based approach and case mapping, which examines: danger/harm; strengths/safety factors; and goals and next steps. The mapping conference was evaluated using mixed methods. Primary results indicate that only 6% of the mapped cases re-opened after a 12-month period. Recommendations from front-line workers include: fully implementing SOS in the investigative process and greater agency support for strength-based practice; including families in the mapping process; and increasing workers' honesty and transparency when engaging with families.

Objectives: To identify factors associated with repeat emergency department (ED) presentations for suicide-related behaviors (SRB)--hereafter referred to as repetition--among children/youth to aid secondary prevention initiatives. To compare rates of repetition in children/youth with substantiated maltreatment requiring removal from their parental home with their peers in the general population. Methods: A population-based (retrospective) cohort study was established for children/youth with a first ED SRB presentation at risk for repetition in the Province of Ontario, Canada between 1 January 2004 and 31 December 2008. Children/youth legally removed from their parental home because of substantiated maltreatment (n = 179) and their population-based peers (n = 6,305) were individually linked to administrative health care records over time to ascertain social, demographic, and clinical information and subsequent ED presentations for SRB during follow-up. These children/youth were described and their repetition-free probabilities over time compared. To identify factors associated with repetition we fit multivariable, recurrent event survival analysis models stratified by repetition and present unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Children/youth with substantiated maltreatment (as noted) were two times more likely to have repetition than their peers after adjustments for social, demographic, and clinical factors (conditional on prior ED SRB presentations). A number of these factors were independently associated with repetition. No one factor distinguished between having a first and second repetition nor was more strongly associated with repetition than another. Conclusions: The risk of repetition is higher in children with substantiated maltreatment (as noted) than their peers. No one factor stood out as predictive of repetition. Implications for secondary prevention initiatives include a non-selective approach, sensitive to family difficulties and the need to better contextualize repetition and harness data linkages. (Contains 2 figures and 2 tables.)

The objective of this study was to describe deliberate self-harming (DSH) characteristics in a child-welfare population identified as having threatened or completed self-harm. Secondary data from 621 serious occurrence reports (SOR) that documented 2004-2007 DSH incidents and DSH threats with 252 Canadian youth in care (Y-INC) of the Children's Aid Society of Toronto (CAS-T) was analyzed. In addition to descriptive analysis, a clustered design binary logistic regression was employed to determine factors associated with DSH characteristics such as repetition, reported behaviour, and severity. Y-INC males (n = 140) made up a slight majority in both DSH categories: single incident of self-harm (sDSH) vs. repeat incidents (rDSH) (55.4% and 56.0% respectively); the female Y-INC sample (n = 112) was responsible for the majority of rDSH incidents (69.1%). Most DSH incidents took place between 6 pm to 12 am, Monday to Friday. Factors found to be associated with DSH in an in-care population of DSH youth were: "non-permanent status" (non-Crown wards were more likely to self-harm vs. threaten self-harm compared to permanent/Crown wards(OR 2.46, CI 1.26-4.80); "older Y-INC" (age 14-21) were more likely to receive medical attention due to a DSH incident vs. 6-13 year olds (OR 4.26, CI 2.51-7.21); and "female Y-INC" were found more likely to have repeat DSH incidents (OR 2.55, CI 1.08-6.02). In addition to heightened supervision and resources for Y-INC that are at-risk for or engage in DSH, greater research attention to this issue is warranted.

Objectives: To determine whether the rates of a first presentation to the emergency department (ED) for suicide-related behavior (SRB) are higher among children/youth permanently removed from their parental home because of substantiated maltreatment than their peers. To describe the health care settings accessed by these children/youth before a first SRB presentation to help design preventive interventions. Methods: A population-based (retrospective) cohort of 12-17-year-olds in Ontario, Canada was established. Children/youth removed from their parental home because of the above noted maltreatment (n = 4683) and their population-based peers (n = 1,034,546) were individually linked to administrative health care records over time to ascertain health service use and subsequent ED presentations for SRB during follow-up. Person-time incidence rates were calculated and Cox regression models used to estimate adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results: After controlling for demographic characteristics and prior health service use, maltreated children/youth were about five times more likely to have a first ED presentation for SRB compared to their peers, in both boys (HR: 5.13, 95% CI: 3.94, 6.68) and girls (HR: 5.36, 95% CI: 4.40, 6.54). Conclusions: Children/youth permanently removed from their parental home because of substantiated child maltreatment are at an increased risk of a first presentation to the ED for SRB. The prevention of child maltreatment and its recurrence and the promotion of resilience after maltreatment has occurred are important avenues to study toward preventing ED SRB presentations in children/youth. Provider and system level linkages between care sectors may prevent the need for such presentations by providing ongoing environmental support. (Contains 1 figure and 4 tables.)