Hospital Queens, Queens, NY.q RSNA, 2014 Purpose:To evaluate the diagnostic performance of previously proposed high-specificity magnetic resonance (MR) imaging-estimated proton density fat fraction (PDFF) thresholds for diagnosis of steatosis grade 1 or higher (PDFF threshold of 6.4%), grade 2 or higher (PDFF threshold of 17.4%), and grade 3 (PDFF threshold of 22.1%) by using histologic findings as a reference in an independent cohort of adults known to have or suspected of having nonalcoholic fatty liver disease (NAFLD). Materials andMethods:This prospective, cross-sectional, institutional review boardapproved, HIPAA-compliant single-center study was conducted in an independent cohort of 89 adults known to have or suspected of having NAFLD who underwent contemporaneous liver biopsy. MR imaging PDFF was estimated at 3 T by using magnitude-based low-flip-angle multiecho gradientrecalled-echo imaging with T2* correction and multipeak modeling. Steatosis was graded histologically (grades 0, 1, 2, and 3, according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system). Sensitivity, specificity, and binomial confidence intervals were calculated for the proposed MR imaging PDFF thresholds. Results:The proposed MR imaging PDFF threshold of 6.4% to diagnose grade 1 or higher steatosis had 86% sensitivity (71 of 83 patients; 95% confidence interval [CI]: 76, 92) and 83% specificity (five of six patients; 95% CI: 36, 100). The threshold of 17.4% to diagnose grade 2 or higher steatosis had 64% sensitivity (28 of 44 patients; 95% CI: 48, 78) and 96% specificity (43 of 45 patients; 95% CI: 85, 100). The threshold of 22.1% to diagnose grade 3 steatosis had 71% sensitivity (10 of 14 patients; 95% CI: 42, 92) and 92% specificity (69 of 75 patients; 95% CI: 83, 97). Conclusion:In an independent cohort of adults known to have or suspected of having NAFLD, the previously proposed MR imaging PDFF thresholds provided moderate to high sensitivity and high specificity for diagnosis of grade 1 or higher, grade 2 or higher, and grade 3 steatosis. Prospective multicenter studies are now needed to further validate these high-specificity thresholds.q RSNA, 2014

Once considered a problem of Western nations, obesity (body mass index ≥30 kg/m) has rapidly increased since the 1970s to become a major threat to world health. Since 1970, the face of obesity has changed from a disease of affluence and abundance to a disease of poverty. During the last 10 years, studies have mechanistically linked obesity and an obese tumor microenvironment with signaling pathways that predict aggressive breast cancer biology. For example, in the United States, African American women are more likely than non-Hispanic European American women to be obese and to be diagnosed with triple-negative breast cancer (TNBC). In 2008, the Carolina Breast Study found that obesity (increased waist/hip ratio) was linked to an increased incidence of TNBC in premenopausal and postmenopausal African American women. Subsequently, several groups have investigated the potential link between obesity and TNBC in African American women. To date, the data are complex and sometimes contradictory. We review epidemiologic studies that investigated the potential association among obesity, metabolic syndrome, and TNBC in African American women and mechanistic studies that link insulin signaling to the obese breast microenvironment, tissue inflammation, and aggressive TNBC biology.

Few susceptibility genes for gastric cancer have been identified. We sought to identify germline susceptibility genes from participants with gastric cancer from an international hereditary cancer research network. Adults with gastric cancer of any histology, and with a germline DNA sample (n= 51), were retrospectively selected. For those without previously identified germline mutations (n= 43), sequencing was performed for 706 candidate genes. Twenty pathogenic or likely pathogenic variants were identified among 18 participants. Eight of the 18 participants had previous positive clinical testing, including six with CDH1 pathogenic or likely pathogenic variants, and two with pathogenic MSH2 and TP53 variants. Of the remaining 10, six were in BRCA1 DNA damage response pathway genes (ATM, ATR, BRCA2, BRIP1, FANCC, TP53), other variants were identified in CTNNA1, FLCN, SBDS, and GNAS. Participants identified with pathogenic or likely pathogenic variants were younger at gastric cancer diagnosis than those without, 39.1 versus 48.0 years, and over 50% had a close family member with gastric cancer (p-values <0.0001). In conclusion, many participants were identified with mutations in clinically-actionable genes. Age of onset and family history of gastric cancer were mutation status predictors. Our findings support multigene panels in identifying gastric cancer predisposition.

During puberty, a woman’s breasts are vulnerable to environmental damage (“window of vulnerability”). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures.

Genetic cancer risk assessment (GCRA) is an interdisciplinary medical subspecialty practice that employs a growing arsenal of genetic and genomic tools to identify individuals and families with increased risk for cancer, often prior to the onset of disease, when early detection or prevention strategies are most effective. Access to GCRA is a standard of care in most developed countries, but is not available in most of Latin America. In March of 2014, City of Hope in Duarte, CA, conducted a roundtable discussion forum with 16 Latin American physicians representing Brazil, Colombia, Mexico, Peru, and Puerto Rico. The purpose of the roundtable was to explore the current state of GCRA services, including policy, resources, and barriers, in the respective Latin American countries. Thirteen participants attended in-person and 3 via web conference. The session was moderated by a team comprised of 4 bilingual cancer genetics clinicians. Participants were prompted with open-ended discussion questions eliciting perceived needs and the current status of GCRA services in their country, barriers to GCRA practice, and possible approaches to address access barriers. The session was largely conducted in Spanish, recorded, and transcribed. The transcript was coded and thematically analyzed. Preliminary analysis identified barriers to GCRA implementation, including: (1) limited patient and provider knowledge about GCRA, (2) lack of insurance coverage and high patient out-of-pocket costs for GCRA testing, (3) long turnaround time for genetic test results, (4) absence of readily available provider training or expertise, and (5) lack of institutional infrastructure or policy to support the development of GCRA programs. Participants emphasized the importance of collecting evidence to support the efficacy of GCRA in their own populations as an essential step toward building GCRA services in their countries. The findings also point to the need for a multi-level approach that addresses the need for education and training and cost-effective genetic testing, as well as the creation of an evidence-based foundation for the development of policy, infrastructure and resources to implement and sustain GCRA services in Latin America. Citation Format: Tanya Chavez, Bita Nehoray, Alexandra Obregon-Tito, Charité Ricker, Ilana Solomon, Mariana Niell-Swiller, Christina Ryback, Julio E. Abugattas, Yasser Sullcahuaman, María F. Noriega, Ana I. Orduz, Jorge M. Melo, Ana Chaves, Lenny Gallardo, Cynthia Villarreal, Robin Shaw, Rosa M. Álvarez, Eunice F. Morales, Alicia M. Cock-Rada, Azucena Del Toro, Pamela Mora, Marcia Cruz, María E. Fernández, Kathleen R. Blazer, Jeffrey N. Weitzel. Exploring the climate, barriers, and possible approaches to implementing genetic cancer risk assessment in Latin America: A roundtable discussion. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A36.