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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.

This work examined the effects of socioeconomic status (SES)-based social identity threat on cardiovascular indexes of challenge and threat and self-regulatory strength. Participants ( N = 104) took an exam described as either diagnostic of intellectual ability (identity threat) or framed as a problem-solving task (control) while we recorded cardiovascular reactivity and assessed participants' physical self-control. Under identity threat, lower SES students exhibited impaired performance, reduced self-control, and cardiovascular threat reactivity. In contrast, higher SES students under threat exhibited the reverse pattern-a boost in performance, no change in self-regulation, and cardiovascular challenge reactivity. Furthermore, while measures of general arousal (heart rate and pre-ejection period) were unrelated to performance, cardiovascular patterns of challenge and threat were significantly associated with performance under identity threat. Results provide evidence that SES-based stigma influences physiological and self-regulatory processes.

Once considered a problem of Western nations, obesity (body mass index ≥30 kg/m2) 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.

The United States (US) is racially and culturally diverse. Still, white women disproportionately comprise clinical trial participants, stemming largely from the fact that minorities often decline participation. Clinical trial findings, therefore, have not been representative of the diverse patient population, and have stymied progress in precision medicine and cancer prevention. According to the CDC, among Asian/Pacific Islander females, the leading cause of death is cancer. Moreover, they have more total cancer-related deaths than any other racial group. Per the 2017 US Census, Asians are the third largest minority group of the population (6.6%). Despite the grave health disparities faced by a sizable proportion of the population, the literature is sparse with regards to their research engagement. For example, several studies have focused on Black and Hispanic consenting rates, including one study that demonstrated no significant differences between the two groups (Wendler, Kington, Madans, Wye, Christ-Schmidt, Pratt et al., 2005) and another that indicated relatively lower enrollment rates among Hispanics and Blacks (Murthy, Krumholz, Gross, 2004). This gap in research is largely due to the marked heterogeneity with respect to language, nationality, and acculturation status. We examined Asian participation in three therapeutic, noninterventional trials that aim to develop early detection methods and accurate prognosis in women at high risk for breast cancer. Primarily, we collect leftover tissue and/or cells from fine needle aspirations (FNA) to better understand the cellular microenvironment that correlates with breast cancer development. We analyzed demographic data across these studies to investigate refusal rates among Asian women. Across the three trials, 3,119 participants were screened. Of the total number screened, 426 participants were eligible, 368 consented, and 58 declined. Of those who declined, 23.5% were Asians, 13.9% Hispanic, 8.3% Blacks, 5.6% Native Americans, and 11.4% White/non-Hispanic. Notably, Asians had the highest refusal rate. Fisher's exact test (two-tailed) was conducted to examine refusal rates for Asians compared to Whites, Blacks, and Hispanics. Results suggest that Asians had significantly higher rates of compared to Whites (p = .02, observed odds ratio = .42, 95% CI [.20, .86]), but were not significantly different than Blacks or Hispanics. The under-representation of Asians in research may exacerbate health disparities. Thus, further studies should examine ways, such as increasing racial and cultural competency, for increasing Asian representation in clinical research studies. Ultimately, we believe that illuminating under-representation of the “forgotten” Asian population in clinical research can inform future interventions that promote chemoprevention and treatment of this high-risk population. Citation Format: Stacey N. Doan, Christine Thai, Angela K. Wong, Tanya A. Chavez, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney Vito, Alan Nunez, Ellen J. Rippberger, Noe R. Chavez, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni M. Idassi, Kendall J. Kennedy, Christopher Sistrunk, Victoria L. Seewaldt. The forgotten race: Under-representation of Asians in clinical research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A084.

Purpose: To highlight the importance of building a high-risk breast cancer clinic for women who do not have a BRCA 1, BRCA 2 or other highly penetrant cancer susceptibility mutation. Background: Breast cancer is the most common cancer in women and the second most prevalent cause of cancer death of women in the United States; the lifetime risk for breast cancer in women is approximately 12%. Women may be at increased risk for breast cancer for many reasons including family history, genetic alterations, age, reproductive status and menstrual history. Most women who are at increased risk of developing breast cancer do not have a BRCA 1, BRCA 2 or other mutation. The majority of breast cancer diagnoses are due to acquired somatic mutations; only 5 to 10% of breast cancer diagnoses are attributable to highly penetrant Mendelian cancer susceptibility genes. White women with Ashkenazi Jewish ancestry tend to have a higher incidence of BRCA 1 and 2 mutations; traditionally, most research efforts about highly penetrant genes have been focused on this group rather than other racial and ethnic groups. However, there is a great need to study breast cancer risk-reduction strategies in racial and ethnic minorities in the United States, particularly because most breast cancers are not caused by BRCA 1 and 2 mutations. City of Hope is located approximately 21 miles northeast of Los Angeles and operates 13 clinical practice locations including Los Angeles, Orange, Riverside, San Bernardino and Ventura counties. These five counties are home to the majority of California's multicultural and ethnic residents where San Bernardino County has the highest percentage of Hispanics (49.9%) and blacks (8.3%), Ventura County has the highest percentage of whites (48.1%), and Orange County has the highest concentration of Asians (18.2%). It has been established in the literature that the greatest benefit from breast cancer prevention strategies comes from treating women who are at high risk of the disease. While it is important to build a high-risk breast cancer clinic for women with genetic mutations, it is equally important to build a high-risk breast clinic for women who are at increased risk of breast cancer but do not have a mutation, particularly because most breast cancer is diagnosed in this population. In addition, it is crucial to educate high-risk patients that although they may have tested negative for a genetic mutation if they have a family history of breast cancer, they warrant close clinical surveillance. Methods: We are proposing a retrospective, descriptive study of data that will be collected as part of a high-risk breast cancer program implemented by City of Hope. Results/Conclusions: We expect to discuss the findings related to serving women of all races and ethnicities who do not have a mutation in a highly penetrant gene mutation. Citation Format: Karen Herold, Lisa D. Yee, Chidimma M. Kalu, Laura L. Kruper, Veronica C. Jones, Amy C. Polverini, Sharon Clancy, Tanya A. Chavez, Jackelyn A. Alva-Ornelas, Noe R Chavez, Ellen J. Rippberger, Jerneja Tomsic, Christopher Sistrunk, Ombeni Idassi, Daniel B. Schmolze, Courtney Vito, Alan Nunez, Angela K. Wong, Krista M. Round, Christine Thai, Angelica Sanchez, Margarita Robles, Kendall Kennedy, Terry Hyslop, Victoria L. Seewaldt. Architecture of increased breast cancer risk [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B109.

Background: Recruiting participants who are representative of the population as a whole is essential to ensure the development of treatments that benefit all rather than a select few. Understanding the reasons patients accept or decline participation, and then making adjustments to the recruiting process based on these findings, is one way to encourage study participation. Aim: To better understand what factors influence a potential participant's decision to either accept or decline participation in breast cancer trials. Methods: These are preliminary data from a pilot study that uses a short questionnaire to investigate which factors influence a woman's consent or decline to study participation. Women are approached for this study after being asked to participate in one of three other breast cancer trials targeting women who either have breast cancer or are at high risk for breast cancer. Women are approached for this study regardless of their decision to participate in the previous study. Participants are asked a set of questions about 1. the specific interaction they had with the consenter from the previous study, 2. general characteristics of a consenter, and 3. research in general. Demographic information is also collected for future analysis of responses based on race/ethnicity, income, education level, and primary language. Results: A total of 24 participants have completed the questionnaire so far, with an accrual rate of approximately 25 patients per month. Participants ranked the importance of the various factors on a 4-point scale with 1 being “not important at all” and 4 being “very important.” Factors that participants indicated were the least important to their decision to participate were: financial compensation (xÌ… 1.07), racial/ethnic parity between consenter and consentee (\bar x $ 1.19), consenter looking like someone from their community (\bar x $ 1.19), gender parity (\bar x $ 1.19), religious beliefs (\bar x $ 1.38), pleasing their doctor (\bar x $ 1.56), and feeling overwhelmed (\bar x $ 1.85). Factors participants indicated were the most important to them were: the desire to benefit others in the future (\bar x $ 3.63), to benefit their family (\bar x $ 3.56), to acknowledge the contributions of past generations (\bar x $ 3.20), the feeling participation was “the right thing to do” (\bar x $ 3.15), presence or lack of potential side effects associated with participation ((\bar x $ 3.15), feeling empowered by the consenter (\bar x $ 3.15), feeling the consenter was listening (\bar x $ 3.11), and trust in research (\bar x $ 3.07). Conclusions: Concerning the consenter, physical characteristics such as race/ethnicity and gender parity were less important than the actual interaction with the consenter, including their flexibility, listening skills, and ability to make the patient feel empowered. For research in general, the idea of contributing to the “greater good” emerged as a powerful motivation to participate. An emphasis on this, as well as well-trained consenters, may help studies attract more participants. Note: This abstract was not presented at the conference. Citation Format: Ellen Rippberger, Noe Chavez, Tanya Chavez, Christine Thai, Angelica Sanchez, Angela Wong, Karen Herold, Alan Nenez, Krista Rounds, Victoria Seewaldt. Factors influencing women's attitudes toward participation in breast cancer clinical research [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A086.

Despite cancer being the leading cause of death across most racial/ethnic groups, Hispanic women have the second highest mortality rate attributed to diabetes (4.7%) according to the Centers for Disease Control and Prevention (CDC). While cancer and diabetes are two distinct diseases, previous studies have demonstrated that diabetic women have a poor chance of breast cancer survival when compared to nondiabetic women. Well-known key drivers of hyperinsulinemia and insulin resistance, such as insulin and AMPK, are also those involved in breast cancer. This link could possibly contribute to the increased mitogenic effects and risk for aggressive breast cancers in Hispanic women. Based on these findings, metformin, a drug standardly used to treat and prevent hyperglycemia, may be a possible alternative (other than tamoxifen) for breast cancer prevention. Eat, Move, Live (EML), a 5-week community-based program, focuses on targeting possible treatments of chronic diseases and risk reduction through attitude and lifestyle modifications. Exercise, nutritional and health awareness classes were implemented to change participants' perspectives regarding chronic diseases and their susceptibility to other morbidities. Questionnaires were given to the participants at baseline and at two follow-ups (5 weeks and 12 weeks) to assess any changes in their attitudes, behaviors, nutrition, lifestyle and beliefs around taking medication for preventative treatments. A total of 56 participants' pretreatment responses were collected via a five-point Likert scale (1-strongly disagree, 5-strongly agree). Demographic data showed that 69% of the respondents were Hispanic women, of whom 46% completed an education level of high school or less. A majority of the responses averaged a “neutral” response to taking medication for management and prevention of diabetes. We infer that their inability to select a stance in their responses may be associated with the lack of knowledge that the community has regarding chronic diseases and risk-prevention methods. Therefore, we anticipate that availability of proper education tools and resources is essential to potentially prevent future morbidities and mortalities. Ultimately, we aim to establish a pilot study that emphasizes the necessity and importance of interventional programs, like EML, to enhance chemoprevention using metformin and improve health outcomes in high-risk breast cancer populations. Citation Format: Mayra Serrano, Angelica Sanchez, Christine Thai, Katty Nerio, Cristal Resto, Marisela Garcia, Tanya A. Chavez, Laura L. Kruper, Veronica C. Jones, Lisa D. Yee, Alan Nuñez, Ellen J. Rippberger, Angela K. Wong, Noé R. Chávez, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Regina Agulto, Margarita Robles, Ombeni M. Idassi, Kendall J. Kennedy, Christopher Sistrunk, Victoria L. Seewaldt. Receptiveness of metformin as a breast cancer prevention drug within the Hispanic community [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B119.

The United States is increasingly racially and ethnically diverse. In fact, California is now a majority-minority region, with a greater percentage of its population comprised of racial minorities than whites. Yet, minorities are continually under-represented in clinical research trials, which provide crucial information on which the future of cancer treatments is built. Without representative inclusion of participants of color in clinical research, we cannot develop effective preventative and treatment approaches for everyone. This current study investigates the factors, including characteristics of study consenters, that may influence women—particularly women of color (WOC)—to accept or decline participation in breast cancer-related trials. We assess these factors through a brief survey, administered to patients immediately after they were invited to participate in a breast cancer-related clinical study. From the beginning of study accrual to the present, twenty-three patients have taken the survey. We anticipate accruing 200 participants at a rate of 25 per month. For the preliminary analyses, we split participants in two groups: white women (WW) (n = 14) and women of color (WOC) (n = 9). We conducted independent sample t-tests to compare the responses of WW and WOC. More WOC (M = 1.44, SD = 0.73) reported that it is important that their consenter is of the same ethnicity or race than WW (M = 1.00, SD = .00), t (21) = -2.32, p < .05. Similarly, WOC (M = 1.44, SD = .73) also reported that it is important that the person inviting them to participate in research look like people in their community, compared to the importance placed on this factor by WW (M = 1.00, SD = .00), t (21) = -2.32, p < .05). More WOC (M = 2.33, SD = 1.23) also cited “feeling overwhelmed” with their medical condition as influential in their decision to participate in clinical research than WW (M = 1.31, SD = .48), t (20) = -2.75, p < .05. Although both groups positively rated their interaction with the consenter, we observed marginal differences between WOC and WW. WOC (M = 7.00, SD = .00) gave higher ratings to the variable of “consenter created an atmosphere of trust and support” compared to ratings given by WW (M = 6.29, SD = 1.07), t (21) = -1.99, p = .06. Though participants are generally satisfied with their consenter interaction, different factors influence WW and WOC as they decide whether to participate in clinical research. When identified, these factors can be used to inform more inclusive consenting processes. Citation Format: Noe R. Chavez, Alan Nunez, Angela K. Wong, Tanya A. Chavez, Ellen Rippberger, Christine Thai, Angelica Sanchez, Ombeni M. Idassi, Krista M. Round, Kendall Kennedy, Margarita Robles, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Chidimma M.K. Kalu, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Courtney Vito, Karen Harold, Terry Hyslop, Carola M. Zalles, Daniel B. Schmolze, Christopher Sistrunk, Victoria L. Seewaldt. Influencing women's attitudes toward participation in breast cancer clinical research: Improving inclusion of women of color [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A082.

Background: Breast cancer (BC) prevention clinical trials (CTs) play a vital role in the progress of preventative measures and treatments for all races and ethnicities. However, Northern European whites (NE/W) continue to be disproportionally enrolled (e.g., 93.5% were non-Hispanic white in the STAR trial), while minorities such as Asians, blacks, Latinas, and Native Americans (NA) lag in participation. Current studies suggest that minorities are not approached as frequently as NE/W; however, they are just as willing to participate. Here we present a successful recruitment strategy to improving minority accrual in CTs at a Comprehensive Cancer Center located in Duarte, CA. Method: Results from community focus groups suggested the need to mentor local youth who strive to pursue a career in the medical field. Consequently, from February 2016 to July 2018, four bilingual, bicultural clinical research assistants (CRAs) were recruited from the catchment area of City of Hope (CoH). The CRAs, in collaboration with seven surgeons, two radiologists, and one medical oncologist, led the recruitment for three nontherapeutic BC prevention CTs at CoH. Results: All four CRAs were 1) first-generation American, 2) fluent in Spanish or Vietnamese, 3) born and raised in Southern California, and 4) pre-health. Of the 3,148 patients who were screened, 398 were eligible for enrollment, 369 consented, and 58 declined. Primary languages and races/ethnicities of those who declined include the following: 7% Armenian, 9% Chinese, 78% English, 2% Thai, and 5% Spanish; 28% Asian, 3% black, 28% Latina, 2% NA, and 67% white (22% NE, 17% Middle Eastern/North African). Demographics of the consenting population include the following: primary language - >1% Armenian, 4% Chinese, 89% English, >1% Korean, and 7% Spanish; race/ethnicity - 14% Asian, 6% black, 30% Latina, 5% NA, and 75% white (40% NE). Of the white population (n = 277), 11% were Middle Eastern/North African, 53% NE, and 36% Latina. Accrual surpassed both the CoH catchment area (11.3% Asian, 8% black, 24% Hispanic, 1% NA, and 32% NE/W) and the CoH interventional/nontherapeutic CT population (10% Asian/Pacific Islander, 4% black, 21% Hispanic, >1% NA, and 55% NE/W). Conclusion: Contrary to current accrual of CTs, here we show that minorities can have a large representation in CT accrual, as long as they are provided the opportunity. Accrual of Asians, Latinas, and NAs exceeded the catchment area and accrual of other CoH CTs. Interestingly, Chinese-speaking women comprised the highest declination group of the non-English speakers, and Asians and Latinas declined the most outside of non-whites. Cultural competency and bilingualism appear to be characteristics of a CRA that may help in accruing minority women into CTs. Our findings suggest that they are just as willing to participate, and the first step is to simply ask. Citation Format: Tanya A. Chavez, Christine Thai, Angelica Sanchez, Laura L. Kruper, Veronica C. Jones, Sharon Clancy, Amy C. Polverini, Lisa D. Yee, Courtney A. Vito, Noé R. Chávez, Alan Nuñez, Ellen J. Rippberger, Angela K. Wong, Karen Herold, Chidimma M.K. Kalu, Jackelyn A. Alva-Ornelas, Jerneja Tomsic, Krista M. Round, Margarita Robles, Ombeni Idassi, Kendall J. Kennedy, Terry Hyslop, Carola M. Zalles, Christopher Sistrunk, Victoria L. Seewaldt. Diversifying breast cancer clinical trial accrual: An approach to recruitment at a Comprehensive Cancer Center [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A083.

This work examined the effects of socioeconomic status (SES)-based social identity threat on cardiovascular indexes of challenge and threat and self-regulatory strength. Participants ( N = 104) took an exam described as either diagnostic of intellectual ability (identity threat) or framed as a problem-solving task (control) while we recorded cardiovascular reactivity and assessed participants' physical self-control. Under identity threat, lower SES students exhibited impaired performance, reduced self-control, and cardiovascular threat reactivity. In contrast, higher SES students under threat exhibited the reverse pattern-a boost in performance, no change in self-regulation, and cardiovascular challenge reactivity. Furthermore, while measures of general arousal (heart rate and pre-ejection period) were unrelated to performance, cardiovascular patterns of challenge and threat were significantly associated with performance under identity threat. Results provide evidence that SES-based stigma influences physiological and self-regulatory processes.

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.

Once considered a problem of Western nations, obesity (body mass index ≥30 kg/m2) 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.

Purpose: Access to genomic cancer risk assessment (GCRA) is standard of care in most developed countries, but is not readily available in Latin America. Following needs assessment, a dissemination and implementation intervention, including clinical training and application of inexpensive genomic tools, was used in Mexico to develop a model for vertical integration of GCRA among underserved populations in Latin America. Methods: A roundtable forum with 15 Latin American physicians representing Brazil, Colombia, Mexico, Puerto Rico and Peru was conducted to assess the state of GCRA services and barriers to implementation in these countries. The roundtable was conducted in Spanish, moderated by bilingual cancer genetics clinicians, recorded, transcribed, translated and thematically analyzed. The training resources of the City of Hope Clinical Cancer Genomics Community of Practice (CCGCoP), a flexible, multi-modal program of distance didactics, face-to-face case-based workshops and continuing practice support, were deployed to promote practitioner level GCRA competence among clinicians in Latin America. A common prospective registry protocol was implemented via the Cancer Genetics Community Research Network (CCGCRN), and an inexpensive BRCA screening tool (HISPANEL) was introduced to support GCRA services. HISPANEL sensitivity compared to full sequencing was estimated; quality/content of GCRA process was assessed; and downstream barriers to follow up care were identified. Results: Roundtable findings pointed to the need for a multi-level approach with GCRA training, cost-effective genetic testing, and an evidence-based foundation to support the development of policy, infrastructure and resources to implement and sustain GCRA services in Latin America. Post-training assessments for the 41 Latin American clinicians indicated significant increases in professional self efficacy and skills, and demonstrate the value of CCGCoP training and practice support; 19 alumni (representing 7 sites in Mexico, Peru, Colombia, Brazil and Puerto Rico) joined the CCGCRN. To date 1,010 patients have been accrued to the Latin American component of the CCGCRN cohort. The HISPANEL genomic tool demonstrated a clinical sensitivity of 68-77%, at a cost of $20 per case in Mexico, where site assessments demonstrated successful initiation of GCRA services and facilitated identification of barriers to follow up care. Conclusions: Innovative pairing of multi-modal GCRA training and practice support, combined with access to affordable genomic screening tools, demonstrates the potential for dissemination and implementation of GCRA to improve cancer prevention and control in Latin America. Future directions: address scalability; adapt to other countries; and develop a Spanish-language version of the training program to facilitate broader dissemination. Citation Format: Jeffrey N. Weitzel, Cynthia Villarreal-Garza, Kathleen R. Blazer, Josef Herzog, Danielle Castillo, Tanya Chavez, Lenny Gallardo-Alvarado, Talia Wegman, Rosa Alvarez, Karla Unger, Maria Fernandez, Azucena del Toro-Valero, Adrian Daneri Navarro, Abelardo Meneses, Luis Herrera Montalvo, Alejandro Mohar Betancourt, Lily van Tongeren, Cancer Genomics Community Research Network. Dissemination and implementation of genomic cancer risk assessment in Latin America via innovative pairing of clinical training and genomic tools. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3465.

Genetic Cancer Risk Assessment (GCRA) clinical referral and testing guidelines are limited for individuals and families with gastric cancer. In part, this is due to a lack of knowledge regarding hereditary gastric cancer susceptibility. The Clinical Cancer Genomics Community Research Network registry includes over 15,000 families seen for GCRA at City of Hope and 45 other collaborating sites. The purpose of this research was to identify variants conferring inherited gastric cancer susceptibility for individuals and families in our registry without previously known genetic predisposition. Adult research participants from our IRB-approved registry with a DNA sample and a personal history of gastric cancer were selected. Those with a previously identified genetic predisposition were excluded (n = 8). In families with more than one eligible individual, the individual with earliest onset of disease was selected. All histologies were included (i.e., intestinal and diffuse adenocarcinomas, as well as, gastrointestinal stromal tumors). Of 47 eligible participants, 22 had previously uninformative clinical testing. Germline sequencing was completed using a novel 706 candidate cancer gene panel, which included genes involved in DNA damage response, cell cycle regulation, apoptosis, and the Fanconi anemia, mTOR, JAK-STAT, and RAS-MAPK pathways; known cancer susceptibility genes; and genes frequently mutated in gastric tumors (data from the Catalog of Somatic Variants in Cancer database). Based on 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology Standards and Guidelines, 18 out of 47 research participants had pathogenic or likely pathogenic germline variants. Of the 18, 11 had a first- or second-degree relative with gastric cancer. Variants were identified in established cancer susceptibility genes, such as BRCA2, BRIP1, RAD51C, ATM, FLCN, as well as in genes from rare autosomal recessive conditions, such as FANCC. In conclusion, using a 706 gene panel to test a GCRA cohort, we were able to identify potentially pathogenic variants in 38% of participants with gastric cancer, with nearly half of these variants in clinically actionable genes. The variants identified in this study will need to be further evaluated using segregation studies, tumor studies, and in larger cohorts to establish causality. Citation Format: Thomas P. Slavin, Kai Yang, Sharon Sand, Tanya Chavez, Danielle Castillo, Joseph Herzog, Ilana Solomon, Christina Rybak, Mariana Niell-Swiller, Bita Nehoray, Aaron Adamson, Kathleen Blazer, Susan Neuhausen, Jeffrey Weitzel, Clinical Cancer Genomics Community Research Network. Identifying hereditary gastric cancer predisposition in the clinical cancer genomics community research network. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2551.

Introduction: Genetic cancer risk assessment (GCRA) is a growing subspecialty that identifies individuals at risk for hereditary predisposition to cancer. Despite recognition of GCRA as a standard-of-care service, there are significant disparities in access to GCRA among at-risk underserved Latina women. Therefore, little is known about the emotional and decisional experience of Latinas undergoing GCRA. Previous studies have looked at the concept of perceived personal control (PPC) as an outcome variable of GCRA, measuring an individual's feelings of control related to the possibility of having a hereditary condition. This study examined PPC among patients participating in a randomized controlled study examining the effect of an adapted motivational interview (AMI) pre-GCRA telephone intervention to promote uptake of GCRA by underserved Latinas. Purpose: To evaluate the influence of the AMI intervention and GCRA on PPC at baseline, immediately pre- and post-GCRA among English and Spanish-speaking Latinas at risk for hereditary breast and ovarian cancer. Method: Eligible participants were adult women who self-identified as Latina, understood English and/or Spanish, and met NCCN criteria for BRCA1 and BRCA2 testing. Participants were randomized to a motivational interview intervention, time and attention control, or usual care. A validated 9-item instrument to assess three dimensions of perceived personal control (behavioral, decisional, and cognitive control) over a genetic problem and the counseling process was translated to Spanish and verbally administered in the patients' preferred language at baseline (prior to randomization) and immediately pre and post-GCRA. A higher PPC score indicates an increased sense of PPC. The three dimensions of PPC encompass a total PPC score. Results: Of the 411 participants, 323 (78.6%) were affected by breast cancer and 88 (21.4%) were unaffected at time of enrollment. Two-hundred and eighty-two (68.6%) were Spanish-speakers and 129 (31.4%) spoke English. While not significant, total PPC scores increased from baseline to post-GCRA and from pre-GCRA to post-GCRA, but decreased from baseline to pre-GCRA for all participants (the affected and unaffected individuals, including English and Spanish-speakers). Unaffected women had significantly higher total PPC scores than women affected with cancer (p=0.001). Unaffected patients had higher cognitive PPC scores at baseline (p=0.008), pre-GCRA (p=0.019), and post-GCRA (p=0.001) compared to the affected participants at all three time points. Unaffected individuals scored higher in behavioral PPC at post-GCRA than the affected participants (p=0.012). The unaffected individuals scored higher in decisional PPC at post-GCRA compared to the affected individuals (p=0.005). There were no significant differences in PPC scores between English and Spanish-speaking participants or between study arms. Conclusion: Cognitive, decisional, behavioral, and total PPC scores were highest at post-GCRA among all groups (unaffected and affected individuals, and English and Spanish-speakers). Unaffected individuals had higher cognitive PPC scores at all three times points compared to affected participants. Interestingly, the affected participants scored higher in behavioral PPC at baseline, but scored lower post-GCRA compared to those who are unaffected. This suggests that after receiving information during GCRA, the unaffected individuals may believe that they have more control over their health and opportunities for cancer prevention. Decrease in total PPC from baseline to pre-GCRA may be associated with pre-counseling anxiety. More investigation into the three dimensions of PPC should be conducted in order to better understand their distinctions and relationship to GCRA. Citation Format: Tanya A. Chavez, Bita Nehoray, Charité Ricker, Kathleen R. Blazer, Sharon Sand, Kimlin T. Ashing, Jaime Cordova, Gwen Uman, Kai Yang, Nancy Feldman, Jeffrey N. Weitzel. Differences in perceived personal control among Latina women undergoing genetic cancer risk assessment for hereditary breast and ovarian cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A50.

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.

Background: BRCA1 and BRCA2 (BRCA) mutation prediction models are low cost tools that enable clinicians to target individuals with a higher probability to carry mutations in the BRCA genes. Most of the data used to construct these models were derived from a predominantly non-Hispanic White population. The predictive accuracy of these models in diverse populations is unclear. The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) was developed using population-based families with multiple affected individuals that were primarily from the UK. The purpose of this study was to investigate and compare the accuracy of BOADICEA for prediction of BRCA mutation status among US Hispanics and a cohort of Mexicans in Guadalajara and Mexico City. Methods: Hispanic patients undergoing genetic cancer risk assessment (GCRA) were enrolled in an IRB-approved prospective registry from sites within the Clinical Cancer Genetics Community Research Network (CCGCRN), comprised of the City of Hope and 47 collaborating sites representing primarily community-based oncogenetic practices across the US and Latin America, including two cancer institutes in Mexico (University of Guadalajara; Instituto Nacional de Cancerología, Mexico City). Pedigrees were created in Progeny, exported to text files, and then uploaded for probablity calculations according to BOADICEA version 3 guidelines. Accuracy was assessed using an observed versus expected and an area under the receiver operating characteristic (ROC) curve analysis. Results: Overall, BOADICEA performed better in US Hispanics (area under the curve [AUC] = 0.75) for predicting a BRCA mutation than in the Mexican cohort (AUC = 0.64; p-value = 0.0015). Although BRCA mutations were documented in 238 of 1,247 (19.1%) US Hispanics and 23 of 234 (9.8%) Mexicans, BOADICEA predicted a mean mutation probability of 10.3% and 5.6%, respectively. Summary: Though generally the best performing model, BOADICEA's ability to predict BRCA mutations has been investigated in previous studies with different populations with varying results. The lower performance of BOADICEA in the Mexican cohort could be a result of the limitations in pedigree data. It's possible that families don't share information about cancer due to cultural norms or fear of stigmitation. It is also possible that the model assumptions about population mutation frequency are inaccurate. The results of this study indicate the need to document the clinical reliability of probability models when evaluating high risk US Hispanics and patients in Mexico. Citation Format: Jessica Clague, Cynthia Villarreal-Garza, Adrian Daneri Navarro, Alexandra J. Obregon-Tito, Sharon Sand, Tanya A. Chavez, Bita Nehoray, Lacolle Robinson, Lenny Gallardo, Azucena Del Toro, Rosa Alvarez, Kathleen R. Blazer, Blu Yanez, Charité Ricker, Gary W. Unzeitig, Kai Yang, Jeffrey N. Weitzel. Evaluation of the BOADICEA model for predicting BRCA1 and BRCA2 mutation carrier probabilities in high-risk US Hispanic and Mexican families: A report from the Clinical Cancer Genetics Community Research Network. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2761. doi:10.1158/1538-7445.AM2015-2761