AbstractAfrican American Research Articles

Abstract B006: Developing Men Moving Forward, a lifestyle intervention for African American prostate cancer survivors

Abstract African American men are disproportionally affected by high prostate cancer incidence and mortality, and also comorbidities. African American prostate cancer survivors (AAPCS) report lower quality of life (QOL) relative to Non-Hispanic white (NHW) survivors. Many factors drive these differences, including weight status and health behaviors. The American Cancer Society has nutrition and physical activity guidelines to help cancer survivors achieve optimal health and QOL. AAPCS are more likely than NHW survivors to be non-adherent. Poor diet and physical inactivity often result in adverse body composition (high adiposity, low lean muscle) leading to hormonal changes, increased systemic inflammation and insulin resistance theorized to promote carcinogenesis and chronic diseases. Studies document positive results for lifestyle interventions focusing on NHW prostate cancer survivors, but inclusion of AAPCS is limited. We conducted an exploratory mixed methods study with AAPCS to inform the development and implementation of Men Moving Forward, a lifestyle intervention currently being tested in a randomized efficacy trial. Methods: 22 AAPCS completed a focus group and validated questionnaires on diet, physical activity patterns, QOL, and unmet needs related to lifestyle changes. Results: 75% of the participants were overweight/obese, 82% were considered insufficiently active, only 10% engaged in resistance training. Diets were high in saturated fat and sugar, low in fiber, fruits and vegetables. Compared to other prostate cancer survivors, AAPCS reported lower rankings on all QOL domains. Compared to the general population, men had worse physical functioning, pain interference, and sexual functioning. Qualitative data reflected high interest in a lifestyle intervention that would provide opportunities to build strength, learn about healthy eating, and bring men together to talk about relevant survivorship issues. Conclusions: Interventions are needed to address the lifestyle and QOL needs of AAPCS. The community-based Men Moving Forward trial will examine the feasibility and effects of a 4-month lifestyle program with 200 AAPCS. Outcomes include body composition (adiposity, lean muscle mass), behavior (diet, physical activity), strength, biomarkers of general health (lipids, blood pressure, glucose, and insulin) and prostate cancer recurrence (inflammation, insulin resistance, hormones) and QOL. This study is being conducted in partnership with the Milwaukee Public Recreation system which increases the potential for program sustainability. Citation Format: Jamal A. Jarrett, Lauren Matthews, Patricia Sheean, Kathryn Flynn, Kathryn Bylow, Deepak Kilari, Paula Papanek, Tina Johnson, Melinda Stolley. Developing Men Moving Forward, a lifestyle intervention for African American prostate cancer survivors [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B006.

Abstract PR06: Research on prostate cancer in men of African ancestry: Defining the roles of genetics, tumor markers, and social stress

Abstract African American men have a >60% higher incidence and are more likely to be diagnosed with aggressive prostate cancer than white men. The reasons are not clear but are likely to include a multitude of factors such as social factors (e.g., lifetime stress), inherited susceptibility, and tumor-related features such as somatic alterations and local inflammation in the microenvironment. To investigate these hypotheses, over the next five years, we will establish a large, national, population-based cohort study, RESPOND (Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Tumor Markers and Social Stress) of 10,000 African American men with incident prostate cancer identified through nine U.S. cancer registries from states that include 38% of all African American prostate cancer cases in the U.S. We will also recruit men who wish to volunteer through our website (RespondStudy.org). The cohort will provide comprehensive information on 1) multilevel stressors over the lifecourse; 2) geographic data on residential segregation, and social and built environmental factors; 3) lifestyle factors and health behaviors; 4) disease-specific factors including PSA screening history and treatment choice; 5) germline DNA to study genetic susceptibility; and 6) tumor samples to study somatic changes associated with aggressive disease. No previous study has attempted to obtain information across these domains in a single large cohort in order to understand the independent and joint contributions of these factors. Leveraging the RESPOND resource and investigator expertise, we have designed a research program composed of four Projects that are supported by four Cores, which are all focused on the central theme of identifying social and biologic factors related to prostate cancer disease aggressiveness in African American men. These Projects include the investigation of multilevel social stressors across the lifecourse in relationship with aggressive prostate cancer (Project 1); genome-wide discovery efforts of germline susceptibility loci for aggressive prostate cancer and examination of the relationship between germline and somatic variation (Project 2); the identification of underlying somatic alterations in prostate cancer tumors and biologic pathways that are related to aggressive disease (Project 3); and a detailed assessment of inflammation in the tumor microenvironment as it relates to prostate cancer aggressiveness (Project 4). Each of the four Projects addresses a distinct research domain, but together they will provide a comprehensive picture of the major factors that contribute to aggressive prostate cancer in African American men. The information we will discover is likely to help in explaining prostate cancer health disparities and have immediate clinical implications in the areas of improved patient stratification and personalized medicine for African American men. This abstract is also being presented as Poster C058. Citation Format: Ann S. Hamilton, Scarlett Gomez, Xiao-Cheng Wu, Kevin Ward, Melissa Bondy, Rosemary Cress, Jennifer Beebe-Dimmer, Karen Pawlish, Jong Park, Iona Cheng, Antoinette Stroup, Thomas Sellers, Susan Gundell, Angelo Demarzo, Denise Modjeski, Stephen Chanock, Salma Shariff-Marco, Mindy DeRouen, John Carpten, Franklin Huang, Karen Sfanos, Tamara Lotan, David Conti, Christopher Haiman. Research on prostate cancer in men of African ancestry: Defining the roles of genetics, tumor markers, and social stress [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 PR06.

How Do African-American Community Members' Perceptions About Environmental Risks of Breast Cancer Compare with the Current State of the Science?

African-American (AA) women experience higher mortality from breast cancer than any other racial group. Understanding community-held perceptions of environmental contaminants as risk factors for breast cancer can inform the development of tailored prevention and education efforts for improve health outcomes. Six focus groups were conducted with AA participants in two counties in South Carolina, and themes were identified using open and axial coding. Perceived environmental risks for breast cancer most frequently discussed by participants were compared to findings from published systematic reviews. Frequently discussed environmental risk factors by participants were deodorants containing aluminum, plastics, pesticides, and air and water pollution. While perceptions of aluminum and air pollution as risk factors did not align with the state of the science, perceived risk factors of chemicals in plastics and pesticides were found to be in alignment. There is some congruence between perceived environmental risks for breast cancer within the AA community and the current state of the science; however, there is a need to communicate information that reflects current science regarding commonly held misconceptions. Development of evidence-based, clear, and culturally appropriate messaging that reflects the current state of the science is warranted.

Abstract B26: Comparative analysis of breast tumor microbiome in Black non-Hispanic (BNH) and White non-Hispanic (WNH) women

Abstract African American women are approximately twice as likely to be diagnosed with highly aggressive estrogen receptor-negative (ER-) and TNBC subtypes of breast cancer than Caucasian women. Among biologic factors, microbiota has been implicated in the etiology of several kinds of cancer including breast cancer. Few recent studies have shown that the breast niche-specific microbiota may have a major influence on breast tumorigenesis as shown by a decreased abundance of bacterial species with known immunomodulatory and probiotic effect in paired tumor tissue as compared to normal tissue derived from healthy patients, including different microbiota profiles in different subtypes of breast cancer. To understand whether the breast tissue harbors microbiota profiles that are uniquely race-specific we have analyzed tumor and matched normal and tumor tissue using 16S rRNA targeted sequencing strategy. Two distinct breast tumor types derived from women were included in this study: triple-negative breast cancer (TNBC) and triple-positive breast cancer (TPBC) derived from BNH and WNH women. The data were analyzed for microbiota composition, abundance, and diversity parameters, alpha diversity and beta diversity. The preliminary microbiome analysis revealed specific differences in abundance both at the phylum and genus levels between WNH and BNH women breast tissues; the alpha diversity matric, Shannon index measuring both richness and evenness of microbiota diversity showed differences in microbial diversity between normal breast tumor tissue and the matched normal adjacent to tumor tissue. The microbiota richness was relatively lower in BNH TNBC tumor tissue as compared to its matched normal adjacent to tumor zone as defined by pathologic analysis. In contrast, the microbiota richness was higher in WNH TNBC tumor tissue as compared to its matched normal breast tissue. The multivariate analysis of beta diversity revealed a distinct clustering in BNH and WNH TNBC microbiota between both tumors as compared to normal tissue and BNH as compared to WNH racial groups. Research reported in this publication was supported by the National Institute on Minority Health and Health Disparities of the National Institutes of Health under Award Numbers S21MD012472 and U54MD006882. Note: This abstract was not presented at the conference. Citation Format: Srikantha Thyagarajan, Yan Zhang, Santosh Thapa, Michael S. Allen, Nicole Phillips, Jamboor K. Vishwanatha. Comparative analysis of breast tumor microbiome in Black non-Hispanic (BNH) and White non-Hispanic (WNH) women [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B26.

A COMMUNITY AND TECH-BASED APPROACH FOR HYPERTENSION SELF-MANAGEMENT (COACHMAN)

African American (AAs) are disproportionately affected by hypertension. Developing effective outreach programs with community partners is a major public health priority and ideal to educate, empower, and offer support to self-manage hypertension in AAs. The purpose of this pilot is to investigate the effectiveness of a community outreach program using a technology-based intervention for hypertension self-management (COACHMAN) to improve blood pressure (BP) control. Forty AAs with hypertension will be randomly assigned to COACHMAN or enhanced usual care (EUC). COACHMAN is comprised of four components: self-monitoring of BP; web-based education; nurse counseling; and training on a medication management application. The primary outcome is change in BP from baseline to 3-months. We hypothesize that participants in COACHMAN (compared to EUC) will have better BP control. Findings from this study, if confirmed, will provide knowledge to the scarce literature available on technology-based interventions appropriate to help AAs self-manage hypertension and improve BP control.

STRESS, FAITH, AND HEALTH AMONG BLACK MEN IN MIDDLE AND LATE LIFE

African American men experience extremely high levels of social and psychological stress from unfavorable social and economic circumstances emerging from institutional discrimination and unfair treatment. Stress has been linked to disproportionate risks for illness, disease and premature mortality among this population. But, few studies have examined how African American men manage or cope with stress, and even fewer have assessed how their coping responses have implications for their health. Faith has been considered a stress coping strategy and a growing number of studies explore how religiosity and spirituality have implications for health outcomes. No studies to our knowledge have examined how faith impacts stress and its influence on the health among African American men. The purpose of this chapter is to demonstrate how faith has implications for socio-biologic interactions associated with elevated risk for disease and premature death among this marginalized population.

CHRONIC PAIN SELF-MANAGEMENT PRACTICES AND PREFERENCES AMONG URBAN AFRICAN AMERICAN OLDER ADULTS

African American older adults experience disproportionate burden from disabling chronic pain. Pain self-management interventions for this group are most effective when they integrate culturally-relevant preferences into intervention design. In the STEPS pilot trial, we collected focus group (n=23) and survey (n=57) data from African Americans age 60+ years about pain-management practices. Participants were recruited from the community and reported pain for 3+ months, with intensity >4 (0 to 10 scale). The most frequently-used pain-management strategies were exercise (75%) and prayer/Bible reading (74%). Also commonly used were healthy eating (61%), OTC medications (65%), and herbal supplements (51%). Focus group themes provided more nuanced information, including reasons for avoiding prescription pain medications, positive experiences with topical treatments, the value of movement, and the role of social support. Findings reveal strong engagement in pain self-care in this population. Interventions can build on existing practices by incorporating spirituality and appealing options for physical activity.

THE MEANINGS OF TRUST IN AFRICAN AMERICAN COMMUNITIES AND THEIR ASSOCIATION WITH PARTICIPATION IN DEMENTIA RESEARCH

African American /Black American older adults’ low participation in research reduces the generalizability of research findings and hinders understanding of dementia mechanisms, further widening health disparities. Both the Alzheimer’s Association and the National Institutes of Health have identified recruitment of African Americans with cognitive impairment into dementia research as an area of high priority. Distrust of research and medical institutions is often cited as a barrier to participation of African Americans in dementia research. Therefore, the goal of this study is to better understand African American community members’ expectations associated with trust. We used focus groups and semi-structured interviews to examine the expectations associated with overall trust. We conducted 6 focus groups: 4 with African American older adults and 2 with caregivers of African American older adults with cognitive impairment. We also interviewed 5 African American older adults with cognitive impairment (total n=59). Data were analyzed with content analysis. Five themes emerged: 1) Importance of providing truthful help/information leading to trust; 2) Long relationships leading to trust; 3) Acting efficiently and consistently (e.g., “not fooling around”) leading to trust; 4) Transference of trust (e.g., I can likely trust someone trusted by a trusted person); 5) Difficult to trust because of a harsh social environment. To conclude, trust is a complex belief associated with multiple expectations and relationships. It is critical that researchers understand these expectations related to trust in order to increase recruitment of African American older adults into dementia research.

Comparative Cardiorespiratory Fitness in Children: Racial Disparity May Begin Early in Childhood.

African American (AA) adults are reported to have lower levels of cardiorespiratory fitness (CRF) as compared to Caucasian adults. CRF is linked to cardiovascular morbidity and mortality. We hypothesized that the disparities start early in childhood. This was a retrospective analysis of the cardiopulmonary exercise test (CPET). We included normal healthy children, ≤ 18years of age, who had normal electrocardiograms and normal cardiac function. We excluded patients with congenital heart disease, obesity and suboptimal exercise test. The entire cohort was divided into two groups based on race (Caucasian vs. AA) and then further subcategorized by gender. The cohort of 248 patients had a mean ± SD age of 14.4 ± 2.1years. 158 (60.8%) were males and 158 (60.8%) were Caucasians. Oxygen consumption was higher among Caucasian children when compared to the AA children (48.7 ± 7.9 vs. 45.4 ± 7mL/kg/min, p = 0.01). This racial disparity continued to persist when comparisons were performed separately for girls and boys. Upon comparing the four groups, the AA females were found to have the lowest values of VO2max, exercise time and METS (p = 0.001).Thus, in conclusion, the AA children have significantly lower level of CRF, as measured by VO2max and exercise time. The racial disparity is independent of gender. African American females show the lowest level of aerobic capacity. The findings of our study suggest that the racial disparity in the CRF levels seen in the adult population may begin early in childhood.

1843-P: Reduced Sampling for the Estimation of Hepatic and Extrahepatic Insulin Clearance in Children of Different Ethnicities

African American (AA) children have lower hepatic insulin clearance than European Americans (EA), as obtained with a 25-sample intravenous glucose tolerance test (FSIGT), over 240 minutes (t=0, 2, 3, 4 5, 6, 8, 10, 12, 15, 19, 20, 21, 22, 24, 26, 28, 30, 35, 40, 50, 60, 70, 180, 240 minutes). C-peptide and insulin concentrations were analyzed with a recent model of hepatic (FEL) and extra-hepatic (CLP) insulin clearance. This model has not been tested in a reduced sampling protocol, easier to be performed in larger cohorts. With data from 203 children of both sexes and 3 ethnic groups [55 AA, 88 EA, 60 HA (Hispanic Americans), age 7-13 years, mean BMI = 19 kg/m2, basal plasma glucose = 99 mg/dL, insulin = 78 pmol/L, C-peptide = 511 pmol/L], a reduced 12-sample schedule was examined (t=0, 2, 4, 8, 19, 22, 26, 30, 40, 50, 70, 180 minutes). FEL and CLP from the reduced protocol were strongly correlated with the full one: FEL: r=0.91, p<0.001; CLP: r=0.96, p<0.001. The mean precision of estimates (coefficient of variation, CV) was similar: CVfull=40%, CVreduced=41%. The lower hepatic but not extra-hepatic insulin clearance in AA vs. EA children was still detectable with the reduced sampling (see Figure 1), that provides virtually identical and precise estimates of insulin clearance. This reduced protocol can be used in larger population-based studies. Disclosure F. Piccinini: None. B. Gower: None. J.R. Fernandez: None. R.N. Bergman: Consultant; Self; Zafgen, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DK067426); Nutrition Obesity Research Center (DK56336); National Institutes of Health (M01RR00032)

Serum Biomarkers for Racial Disparities in Breast Cancer Progression.

African American (AA) women are often diagnosed with more aggressive breast cancers and have worse survival outcomes than their Caucasian American (CA) counterparts. However, a comprehensive understanding of this disparity remains unclear. In this study, we attempted to identify the race-specific non-invasive protein biomarkers that may particularly benefit interventions aimed at reducing the risk of recurrence and metastasis in breast cancers (BrCa). Our technical strategy has been to discover candidate protein biomarkers in patient sera using a high throughput antibody microarray platform. A total of 240 subjects were selected, composed of controls and all immunohistochemistry-based subtypes of breast cancer cases, subdivided by pre- and post-menopausal status and by race. A global Wilcoxon analysis comparing no-cancer controls and cancer patients identified Pyk2, SAPK/JNK, and phosphatase and tensin homolog as present in higher concentrations in cancer patient serum. A paired t-test revealed that c-kit and Rb are significantly over-represented in AA cancer serum when compared to CA cancer serum. Interestingly, VEGFR2, a protein linked to BrCa metastasis and poor prognosis, was significantly over-represented in AA cancer serum compared to AA controls; however, this was not found in CA cancer serum compared to CA controls, suggesting a possible explanation for the higher incidence of aggressive BrCa in AA versus CA patients. Through examining race-specific differences in the protein landscape of BrCa patient serum, the identified proteins could lay the groundwork for the development of an all-inclusive "liquid mammogram test."

Perceptions of emotional and physical wellness among African American men as predictors of perceived overall health

ABSTRACT African American are at risk for adverse emotional health. However, due to the intersection of their racial and gender identities which heightens their masculinity, emotional wellness is not always considered a priority by and for these men. This study aimed to examine African American men's emotional and physical health in relation to their overall health. An exploratory cross-sectional study was conducted to examine self-reported responses regarding emotional and physical health as predictors of overall wellness among a convenience sample of 115 African American men. The Wellness Self-Perception Questionnaire (WSPQ), a 15-item scale, was used to assess emotional and physical wellness. Overall health was assessed by a single item. Of the 115 study participants, the majority reported a positive perception of their overall health. Linear regression analyses revealed that both reported emotional wellness and physical wellness predicted better overall wellness, even when controlling for men's education and income. A review of the literature indicates this is the first study to assess emotional and physical wellness as predictors of overall health for African American men. Since African American men tend to utilize physical health services even for mental health concerns, implications for physicians are also discussed.

Abstract A089: Challenging the free hormone hypothesis for vitamin D in the prostate has implications for the prostate cancer disparity in African American men

Abstract African American (AA) men are disproportionately at risk for both prostate cancer (PCa) and vitamin D (vitD) deficiency compared to European American (EA) men. Based on the numerous chemopreventative properties of vitD and its status with PCa aggressiveness and mortality, vitD deficiency has been hypothesized as a biologic contributor to the PCa disparity in AA men. We recently reported that despite having deficient levels of vitD in the serum, AAs have higher levels of vitD in their prostate tissue compared to EAs. This suggests a mechanism of active vitD transport across the membrane and challenges the longstanding free hormone hypothesis, which asserts that the activity of a hormone is due to the bioavailable fraction and its passive diffusion across the membrane. The majority of VitD circulates bound to D binding protein (DBP) and is sequestered in the serum, rendering it unavailable for passive diffusion. A mechanism of active DBP-vitD endocytosis has been well characterized in the kidney by the extracellular receptor megalin. We hypothesized that megalin is functional in prostate epithelium and facilitates adequate prostatic vitD levels in AAs with vitD deficiency. Here, we report megalin protein expression in prostate tissue, LNCaP, and primary human prostate cells. Megalin function was further assessed in primary human-derived organoids treated with 25D in the presence or absence of DBP. Surprisingly, vitD import and metabolism occurred faster in +DBP conditions and suggests that DBP-vitD active transport is more efficient than passive diffusion of vitD alone. VDR activation was diminished in a dose-responsive manner by addition of a megalin antagonist. Additionally, megalin protein levels in PCa were significantly lower compared to benign (p<0.05) on a tissue microarray quantified by immunofluorescent staining. In summary, our data support a model of megalin-mediated active transport for vitD in the prostate and demonstrate ancestry-related and PCa differences in megalin regulation. These findings challenge the free hormone hypothesis and postulate that vitD deficiency is more complex than previously thought. Citation Format: Zachary Richards, Larisa Nonn. Challenging the free hormone hypothesis for vitamin D in the prostate has implications for the prostate cancer disparity in African American men [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A089.

Abstract B92: Metabolomic landscape of African American prostate cancer: Insights into the biologic basis of the racial disparity

Abstract African American (AA) men have an approximately 60% higher incidence of prostate cancer (PCa) and have about two times greater risk of dying of the disease than their European American (EA) counterparts. Despite this staggeringly unequal burden of PCa incidence and outcome between AA and EA men, there is limited insight into the molecular mechanisms associated with this racial disparity. Using state-of-the-art mass spectrometry platform, we uncovered the very first metabolic and lipidomics landscape in PCa/benign adjacent tissue pairs and paired plasma and urine containing epidemiologic meta-data from ancestry-typed AA and EA men. A total of 190 polar and mid-polar metabolites and 495 lipids were measured in tissues and 183 metabolites and lipids were examined in the plasma and urine samples. AA PCa tissue and plasma signatures had unique alterations in metabolites and key enzymes associated with the methionine-homocysteine pathway, including adenosine and inosine levels, compared to corresponding tissues and plasma from EA case controls and EA PCa tissues. Intriguingly, methionine levels in AA PCa were also portrayed by distinct dietary practices in these patients. In addition, AA PCa tissues demonstrated unique patterns of bioenergetic metabolites and accumulated lipids reflecting impaired mitochondrial activity and TCA cycle. Further characterization of these first-in-the-field findings demonstrating reprogrammed metabolism in AA PCa relative to EA tumors could reveal insights into the biologic basis of PCa disparities and novel areas for therapeutic intervention. Citation Format: Stacy M. Lloyd*, Jie H. Gohlke*, Sumanta Basu*, Vasanta Putluri,Shaiju K Vareed, Rebeca San Martin, Thekkelnaycke Rajendiran, Tiffany A. Dorsey, Bandana Prasad, Rajni Sonavane, Uttam Rasaily, James Henderson, Balasubramanyam Karanam, Harene Venghatakrishnan, Salil Bhowmik, Alexander Zaslavsky,Nilanjan Guha, Rick Kittles, Stefan Ambs, Michael Ittmann,David Rowley, Ganesh Palapattu, Nagireddy Putluri,George Michailidis, Arun Sreekumar. Metabolomic landscape of African American prostate cancer: Insights into the biologic basis of the racial disparity [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B92.

Abstract A64: Immune and metabolic mechanisms regulate the microenvironment in triple-negative breast cancer

Abstract African American (AA) women experience obesity and cancer risks that differ from white women. Obesity prevalence, risk of poor-prognosis triple-negative breast cancer (TNBC), and mortality rate are all higher among AA women. Obesity-driven Type 2 diabetes (T2D) is twice as common in AA women as white women in the U.S. and is associated with 20% increased risk of breast cancer. Differences by subtype are not well understood, yet recent evidence from our group supports a stronger association with ER- cancer. T2D is a systemic, chronic inflammatory disease, with local inflammation of breast adipose tissue that may promote metastasis of breast cancer. Yet about a quarter of AA adults with obesity remain relatively “metabolically healthy” despite obesity, with reduced cardiovascular and T2D risks and lower inflammation; emerging data suggest that this subgroup is also protected from breast cancer. Approach: Inflammation in nondiabetic adults with obesity is not well understood, and the few previous studies in this area only examined traditional markers like interleukin (IL)-6, TNF-α and C-reactive protein. We comprehensively profiled plasma cytokines to develop an unbiased signature of inflammation associated with obesity and T2D in a nonclinical population of AA women with obesity. Methods: Cytokines were profiled from 39 AA women with obesity who donated plasma to the Komen Tissue Bank, divided among women with T2D and matched nondiabetic controls. Multiplex bead arrays of analytes were used to quantify 88 cytokines and chemokines in association with clinical diagnoses of metabolic health. Regression models were generated after elimination of outliers. We functionally validated chemokines in human breast cancer models of migration, invasion, epithelial-to-mesenchymal transition (EMT), and cancer cell “stemness.” Results: Among women with obesity, T2D is associated with breast adipocyte hypertrophy and with six plasma analytes, including four chemokines, CCL2, CCL16, GRO-1, and CXCL16; and two growth factors, IL-2 and epidermal growth factor. In addition, three analytes are associated with obesity independently of T2D: IL-4, soluble CD40 ligand, and CCL3. Several of these factors are associated with aggressiveness of breast cancer in vitro. EMT phenotypes are critically controlled by the BET bromodomain proteins, including BRD2 and BRD4; invasion and migration in TNBC are controlled only by BRD4. These transcriptional coregulators can be inhibited by new small-molecule epigenetic drugs, suggesting a chemoprotective approach for AA women at risk for breast cancer metastasis. Conclusion and Implications: Risks for breast cancer incidence and progression are not distributed evenly, and are likely stratified by abnormal metabolism and its associated chronic inflammation. Yet the current standard of care in breast oncology does not fully consider the role of “immunometabolism” as a driver of metastasis. New noninvasive methods of cytokine and chemokine profiling might improve diagnosis and clinical decision making for underserved patients. Specific inflammatory cytokines and chemokines, which are likely to be critical effectors to drive advanced forms of breast cancer, must be validated in prospective observational studies. Note: This abstract was withdrawn and not presented at the conference. Citation Format: Guillaume Andrieu, Paola Sebastiani, Kimberly A. Bertrand, Julie R. Palmer, Gerald V. Denis. Immune and metabolic mechanisms regulate the microenvironment in triple-negative breast cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A64.

Abstract B70: Thymoquinone regulates cytochrome P450 genes involved in prostate cancer disparity

Abstract African American (AA) men have a higher incidence and greater mortality from prostate cancer (PCa) than Caucasian American (CA) men. The factor influencing the racial disparity is not clearly understood and is probably genetic variation attributed to the disease. Androgen and androgen receptor (AR) pathways have long been associated with prostate growth. Racial differences have also been found among variants of the genes of the enzymes involved in androgen biosynthesis and metabolism, such as CYP3A4, CYP3A7, and CYP17A1. Although several inhibitors are approved for CYPs genes, the major drawback of these inhibitors is they contain the steroid scaffold, which contributes to the undesirable side effects (dyspnea, edema, contusion, etc.) observed in patients. In this regard, using nonsteroid scaffolds such as natural compound acts as a more potent inhibitor and interacts more selectively with the cytochrome P450 family. In this study, our data showed the effect of natural compound thymoquinone (TQ), a constituent of Nigella sativa (black seed), on CYP3A4, CYP3A7, and CYP17A1 genes in PCa cells, and found that TQ-treated cells significantly downregulated the expression of CYP3A4, CYP3A7, and CYP17A1 in MDA PCa 2b and E006AA-hT (African American) compared to LNCaP (Caucasian) cell lines. These findings were further confirmed by flow cytometry, Western blots, and immunofluorescence. These studies suggested that TQ could be the potent inhibitor of the active sites of the cytochrome P450 enzymes, which are an important target in the treatment of PCa. Additionally, knowledge of the PCa susceptibility genes (CYPs) could be used to identify individuals at risk of developing PCa with poor outcomes for heightened screening or prevention modalities and to identify optimal treatment strategies for men of African descent. Citation Format: Santosh K. Singh, James W. Lillard, Jr., Rajesh Singh. Thymoquinone regulates cytochrome P450 genes involved in prostate cancer disparity [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B70.

Abstract B87: [Advocate Abstract:] Prostate cancer survivorship among African American males

Abstract African American survivors of prostate cancer and their families share common experiences yet express their reactions in widely divergent ways. Understanding what factors account for those differences helps explain why some survivors have coped extremely well after treatment and why others have struggled. This research is focused on what enabled victims to become successful survivors and its potential impact on subsequent generations. This study sheds new light on the coping and adaptation of survivors and their families from their own perspective. The study was conducted to describe the lived experiences of African American survivors of prostate cancer, to understand the phenomena in their own terms, to provide a description of their experiences with prostate cancer, and to identify interventions that are ethnically and culturally sensitive. The researcher administered a 49-question sociodemographic survey and conducted 25 in-depth interviews, which entailed descriptions of significant events that influenced the recovery process, perceptions of the health care delivery process and health care providers, and specific recommendations for program development and community outreach in African American communities. Citation Format: Earl Bowen. [Advocate Abstract:] Prostate cancer survivorship among African American males [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B87.

Abstract 3721: MMP9 responsive molecular beacon-loaded nanovesicles for imaging and therapy for triple negative breast cancer

Abstract African American women are disproportionately affected by triple negative breast cancer (TNBC). Combination of tumor chemotherapy and imaging in an ‘all-in-one system' provides a useful multi-modal approach in the battle against metastatic breast cancer. A promising imaging technique, time gated molecular beacon probes, is a noninvasive and painless method for detection and monitoring. Molecular beacon probe-based theranostic nanoparticles is a novel concept in next-generation medicine that combines simultaneous diagnostics and therapeutics to radically change the way we diagnose, image and treat breast cancer. In this study, we formulated pH sensitive nanovesicles containing molecular beacons specific to MMP-9 for imaging tumor microenvironment along with an anticancer drug, thereby enabling visualization of the tumor together with therapy at the tumor site. This theranostic nanosystem will provide an exciting new tool for breast cancer diagnosis and therapy. Formulation of novel pH responsive nanovesicles were carried out using DMPC and DSPE-PG-8CH. Molecular beacons specific to MMP-9, along with cabazitaxel were encapsulated within the nanovesicles. Characterization of the formulated nanovesicles along with intracellular uptake studies were carried out in breast cancer cell lines. The hydrodynamic diameters of the vesicles were measured using a dynamic light scattering (DLS) instrument (Malvern Zetasizer Nano-ZS) and found to be ~65nm. The zeta potential varied between -55 to -60 mV. Validation of molecular beacon loading in liposome and its stability were done using spectroscopy. Results indicated a molecular beacon loading of ≈29 % in the liposomes and the liposomes were stable for atleast 2 weeks. Comparison of cleavage sequence with time MB and MB-loaded liposome showed that even after 72 hours, molecular beacon released from the liposomes were able to cleave MMP-9 and elicit an effect. This unique and innovative combinatorial theranostic strategy can improve the accuracy of imaging and therapy, provide better assessment of the severity of disease and even monitor the response to drug therapy. This innovative proposal of combining an imaging technique together with delivery of anticancer drug at the tumor site will enhance their clinical potential for diagnosis and therapy in metastatic breast cancer therapy. Citation Format: Amalendu P. Ranjan, Rafal Fudala, Sunil Shah, Andrew Gdowski, Piyush Kumar, Ignacy Grycznski, Zygmunt Grycznski, Jamboor K. Vishwanatha. MMP9 responsive molecular beacon-loaded nanovesicles for imaging and therapy for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3721.

Abstract 606A: Biological predictors and the impact of cancer among African American women

Abstract African American women have a lower incidence of breast cancer yet, they have an overall higher mortality rate compared with women of other racial groups. Furthermore, some African American women are more likely to be diagnosed with breast cancer at an advanced stage when compared to other women and are also more likely to have biomarkers that are estrogen and progesterone receptor negative and have a greater propensity to be diagnosed with variant forms of breast cancer when compared with other women. These aforementioned factors may affect a women's quality of life. While the literature is robust with psychosocial and behavioral factors that contribute to the quality of life that African American women experience; to date, there has been a paucity of empirical data that have investigated the role of biological predictors and its effect on the lives of these women. To that end, the specific aim of this study was to test a model and investigate the role of biological risk factors estrogen receptors (ER), progesterone receptors (PR), triple negative breast cancer, Breast CAncer gene (BRCA1/2), Tumor Protein 53 gene (TP53, p53), age <45, Basal Metabolic Index (BMI), and age of first pregnancy that may affect the quality of life, thus having an impact on the lives of African American breast cancer survivors. These factors are hypothesized as impacting the quality of lives of these women and their families. The Impact of Cancer is defined as negative or positive occurrences/after-effects along the breast cancer continuum. The Impact of Cancer (IOCv2) captures the multidimensional aspect of the cancer experience that is specific for cancer survivors and their quality of life. Methods: As part of a larger cross-sectional study, breast cancer survivors completed a demographic data questionnaire inclusive of biological risk factors and the impact of cancer scale. A multiple linear regression was performed to determine the relationship between the two variables. Utilizing recruitment flyers, support groups and word-of-mouth, we recruited and screened 169 women from breast cancer support groups and community dwellers in Southern and Northern California. One hundred and sixty women were eligible and n=155 participated. Inclusion criteria were women who self-identified as African/Black American, age 25 year or older, diagnosis of breast cancer and at least 1-year post-active treatment. Results: Among the biological predictors, none were statistically significant as predictors of the impact of cancer in the lives of these survivors. The results revealed a trend in survivors who were diagnosed before age 45 (p=.077) that their breast cancer experience had a positive impact on their lives.Conclusion: Understanding biological predictors and the unique interplay of these roles may be necessary along the survivorship trajectory. Additional exploration of psycho social predictors and inclusion of specific moderators may be warranted. Citation Format: Claudia M. Davis. Biological predictors and the impact of cancer among African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 606A.

Ethnic Differences in Hepatic Insulin Clearance Seen since Childhood Suggest a Genetic Basis

African American (AA) adult women (AAw) have 1/3 the hepatic insulin extraction as European American adult women (EAw). Lower hepatic (but not extrahepatic) insulin clearance in AAw contributes to hyperinsulinemia. Our aim was to examine whether hepatic insulin clearance impairment exists in AA since childhood. If so, genetic factors might explain ethnic differences in insulin clearance. The FSIGT was performed on 203 children [55 AAc, 88 EAc, 60 HAc (Hispanic American), ages 7-13 years, mean BMI = 19 kg/m2, basal plasma glucose = 99 mg/dL, insulin = 78 pM, C-peptide = 511 pM]. Data were analyzed with a recent mathematical model providing individual estimates of both hepatic fractional insulin extraction (FEL) and extrahepatic insulin clearance (CLP). Results are presented as mean (SD). Two-way ANOVA and ANCOVA were done: sex and ethnicity were used as groups for both the analysis, while age, Tanner stage and body fat from DXA were the covariates. FEL is lower in AAc (19% (20%)) than EAc (33% (20%)), p = 0.0007). Adjusting for the covariates, ethnicity was still associated with lower FEL in AAc vs. EAc (p = 0.0012); sex had a slight but significant effect (FEL=24% (10%) in boys vs. 29% (10%) in girls, p = 0.04). FEL in HAc (28% (21%)) was not significantly different than either AAc or EAc (p>0.05), with or without covariates correction. No correlation between FEL and age was found in these children. Unlike FEL, CLP was not impacted by ethnicity or sex; similar values were observed among the three groups [27 (12), 21 (12), and 24 (28) mL/kg/min for AAc, HAc, and EAc, respectively; p > 0.05]. As the between-group differences in FEL are seen early in childhood, this suggests genetic factors likely contribute to those, rather than lifestyle, that might have a less evident effect at that age, instead. Playing a more important role than previously realized, the reduced insulin degradation would lead to hyperinsulinemia, insulin resistance, and possibly greater risk for type 2 diabetes in AA, compared to other ethnic groups. Disclosure F. Piccinini: None. D. Polidori: Employee; Self; Janssen Research & Development. Stock/Shareholder; Self; Janssen Research & Development. B. Gower: None. J.R. Fernandez: None. R.N. Bergman: Advisory Panel; Self; Ingredion, Inc.. Research Support; Self; AstraZeneca. Consultant; Self; GI Dynamics Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. Consultant; Self; Novo Nordisk A/S.