High-risk African American Women Research Articles

Perceived risk of breast cancer and god health locus of control in high risk African American and caucasian women.

e24142 Background: African American women are more likely than any other racial groups to present with a later stage of breast cancer. Survival rates among African American women with breast cancer are lower than that of their Caucasian counterparts. Studies have shown that women who believe that they can control their health through their own behavior may be more likely to report a lower perceived risk that women who believe that others (such as God or “powerful others” or chance) control their health outcomes. There is a limited body of literature on the effects of spiritual locus of health control and a patient’s perceived risk of breast cancer. Herein, we studied the association between God Locus of Health Control (GLHC) and perceived risk of breast cancer among 85 women recruited from a high-risk clinic. Methods: Consented participants that agreed to the study were asked to fill out the Patient Reported Outcomes Measurement Information Systems (PROMIS) initiative questionnaire. The PROMIS initiative standardizes measurements of psychosocial research in cancer to address major shortcomings in this field. The questionnaire includes demographic characteristics, perceived risk of breast cancer, and questions regarding spiritual and GLHC. Differences in patient demographics (including race), perceived risk, and multivariate testing was performed. Results: When asked to rank their chances of developing breast cancer in their lifetime, Caucasian participants were statistically more likely to respond with a higher perceived risk than African American participants (p = 0.01). Caucasian participants were more likely to respond with a higher perceived risk score when asked to compare their chances of developing breast cancer to that of the average woman their age (p = < 0.001). Linear regressions correlating perceived risk, degree of GLHC and race did not show any statistical significance. Multivariate analyses only showed race was a statistically significant predictor of any of the perceived risk variables. Our study showed that Caucasian participants were more likely to have a lower GLHC score than their African American counterparts and were more likely to perceive a higher risk of developing breast cancer. GLHC was not statistically significantly associated with any of the 4 perceived risk measures (p > 0.05 for all). Conclusions: Overall, there was not a statistically significant relationship between GLHC scores and perceived risk. Further larger-scale studies will be needed to further characterize these findings.

When the At-Risk Do Not Develop Heart Failure: Understanding Positive Deviance Among Postmenopausal African American and Hispanic Women

African American and Hispanic postmenopausal women have the highest risk for heart failure compared with other races, but heart failure prevalence is lower than expected in some national cohorts. It is unknown whether psychosocial factors are associated with lower risk of incident heart failure hospitalization among high-risk postmenopausal minority women. Using the Women's Health Initiative Study, African American and US Hispanic women were classified as high-risk for incident heart failure hospitalization with 1 or more traditional heart failure risk factors and the highest tertile heart failure genetic risk scores. Positive psychosocial factors (optimism, social support, religion) and negative psychosocial factors (living alone, social strain, depressive symptoms) were measured using validated survey instruments at baseline. Adjusted subdistribution hazard ratios of developing heart failure hospitalization were determined with death as a competing risk. Positive deviance indicated not developing incident heart failure hospitalization with 1 or more risk factors and the highest tertile for genetic risk. Among 7986 African American women (mean follow-up of 16 years), 27.0% demonstrated positive deviance. Among high-risk African American women, optimism was associated with modestly reduced risk of heart failure hospitalization (subdistribution hazard ratio 0.94, 95% confidence interval 0.91-0.99), and social strain was associated with modestly increased risk of heart failure hospitalization (subdistribution hazard ratio 1.07, 95% confidence interval 1.02-1.12) in the initial models; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among 3341 Hispanic women, 25.1% demonstrated positive deviance. Among high-risk Hispanic women, living alone was associated with increased risk of heart failure hospitalization (subdistribution hazard ratio 1.97, 95% confidence interval 1.06-3.63) in unadjusted analyses; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among postmenopausal African American and Hispanic women, a significant proportion remained free from heart failure hospitalization despite having the highest genetic risk profile and 1 or more traditional risk factors. No observed psychosocial factors were associated with incident heart failure hospitalization in high-risk African Americans and Hispanics. Additional investigation is needed to understand protective factors among high-risk African American and Hispanic women.

Abstract A046: Collecting nonclinical data to address disparities in cancer prevention: Lessons from the field

Abstract Background and Purpose: Research on how women at high-risk of breast or ovarian cancer make risk-reduction choices is still developing, and rarely addresses minority and underserved populations. Early findings indicate that African American women face additional burdens at every stage of the decision-making process. Because most high-risk African American women do not receive clinical care related to risk, further research requires recruitment methods that do not rely on the clinical populations commonly used in risk-reduction studies. Procedures: The Daughter, Sister, Mother Project has recruited high-risk African American and White women from non-clinical environments to collect both qualitative (semi-structured interview) and quantitative (survey) data. Non-clinical recruitment methods include contacting women through social media, online volunteer databases, and community organizations. They present unique challenges for which we have developed specific solutions. Results: Our experience recruiting non-clinical but high-risk populations has yielded solutions that may be useful to other researchers. (1) Risk prediction modeling. Because the individual risk level of women recruited through non-clinical methods is usually unknown, risk prediction modeling must be built into the data collection process. Telephone screening by trained research staff allows risk prediction modeling before study enrollment, and replaces the risk-level information that would pre-exist participant recruitment in a clinical setting. Collecting risk-related information within a survey instrument makes it possible for participants to complete a survey in one interaction, but requires risk-prediction modeling and sample trimming after the data have been collected. (2) Hacking and fraudulent accounts. Combining online data collection with social media recruitment facilitates the involvement of participants not commonly drawn into biomedical research, but also exposes studies to hackers and fraudulent participants. To avoid (a) losing incentive funds to hackers and (b) incorporating fraudulent information into study datasets, we have developed methods to distinguish “real” from “fake” participants. These include survey programming methods that detect or weed out fraudulent accounts, semi-automated methods to locate impossible data combinations, and direct phone contact with participants after data collection is complete. (3) Ongoing connections. Some African American women not already involved in high-risk clinical care are also hesitant to become involved in health-oriented research. Trust can be built through connections with community organizations, fostering ongoing two-way contact with our research team, and returning useful information to the communities where we learn it. Conclusion: Recruitment of non-clinical populations is a useful tool for cancer health disparities research, and requires creative recruitment, data collection, and data cleaning methods. Citation Format: Tasleem J Padamsee. Collecting nonclinical data to address disparities in cancer prevention: Lessons from the field [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 A046.

Promoting genetic counseling among African American women with hereditary risk for breast cancer.

e13639 Background: Breast cancer (BC) mortality is substantially higher for African American (AA) women compared to their white counterparts. Genetic counseling (GC) is a key step in management of women with hereditary BC risk, but medically underserved women of color are less likely to receive these services. We report preliminary data from a pilot study examining the impact of a culturally sensitive, multimedia educational video created to motivate AA women with hereditary BC risk to attend GC. Development of the intervention was guided by the Integrative Model of Behavioral Prediction and qualitative research with the target audience. Methods: AA women eligible for GC for hereditary BC according to national criteria were identified through cancer genetic risk assessment (CGRA) performed at the time of a screening mammogram at the University of Illinois Health System in Chicago, IL, and were invited to participate in the study. Participants completed a baseline survey, viewed the educational intervention, and completed a post-intervention survey. The surveys included five-item Likert scales on intentions to act on the information presented, normative beliefs about GC, knowledge, and acceptability of the intervention. Responses were summarized as frequencies and proportions, and changes pre/post-intervention were evaluated using McNemar’s test. Results: The proportion of participants (n = 30) who rated they were “Extremely Likely” to make an appointment with a genetic counselor increased from 50% at baseline to 70% following the intervention (p = 0.04). After viewing the video, the proportion who rated they were “Extremely Likely” to speak with their doctor about genetic counseling increased from 60% to 77% (p = 0.10). There was a 16.6% increase (p = 0.05) in the proportion of women who indicated their family would be interested in learning more about GC, and 96.6% and 90% of participants agreed that the intervention video was enjoyable to watch and that they could relate to what the actors were saying, respectively. Changes in intentions to act on the information presented were not accompanied by changes in knowledge. Conclusions: A culturally sensitive multimedia intervention based on a theoretical model of health behavior increased intentions to attend GC among high risk AA women. The intervention was enjoyable for minority women to watch and increased intentions to discuss GC with family members. These findings indicate that culturally tailored motivational interventions have the potential to increase uptake of GC in underserved communities.

Annexin 2 protein expression is associated with breast cancer subtypes in African American women

BackgroundA review of literature on the expression of Annexin 2 in cancer has shown that there is very limited research work on the association of this protein with breast cancer aggressiveness in African Americans. In the present study, TMA breast tissues from African American women were stained with Annexin 2 antibody to determine the association between the molecular subtypes and Annexin 2 protein expression. MethodAn annotated case series of 135 breast cancer tissues archived from 2000 to 2010 was acquired from the Howard University Tumor Registry. The association between ANX2 expression and survival by molecular subtypes Luminal A, Luminal B, HER2, and Triple Negative (TN) was assessed using Multinomial regression, chi-square analysis, and Kaplan-Meir graphs (Stata 11). ResultsOur findings show a marked association between ANX2 protein expression in Luminal B and HER2 subtypes unadjusted and when adjusted for age. Borderline differences in tumor grade were found in TN only.Univariately, age (<50, 50 + years) and metastases were highly significant for overall survival, disease-free survival and recurrence-free survival. Stage, tumor size, and nodal involvement were of borderline or greater significance for overall and disease-free survival. ANX2 expression was not significant. Kaplan Meier tests of ANX2 showed significant separation of overall survival by ANX2 protein expression in all breast tumor subtypes. In multivariate analyses comparing TN to Luminal A, ANX2 was not important while controlling for age and grade. ConclusionANX2 might be a biomarker of aggressiveness and a relevant candidate biomarker in high risk African American women with Luminal B and HER2 breast cancer.

Abstract 4175: Spectrum of heritable mutations in 43 known and candidate breast cancer susceptibility genes in African American women with breast cancer

Abstract Mutations in twenty genes have been associated with heritable breast cancer (BCA), yet the prevalence and clinical implications of most of these genes have not been well described in African American women (AAW). AAW who harbor inherited mutations in BCA susceptibility (BCS) genes are less likely to be identified and thus less likely to receive standard of surgical and preventive care for heritable BCA. A better understanding of heritable mutations in AAW with BCA would ultimately help to define guidelines for clinical management of high risk AAW. We performed targeted sequencing for 288 AAW diagnosed with invasive BCA unselected for family history, age, or BCA subtype. Participants were enrolled in the Detroit Research on Cancer Survivors (ROCS) cohort study or the Karmanos Cancer Institute Biobank. A custom sequencing panel captured the coding sequence of 43 genes (Known: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MRE11A, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53; Candidate: MLH1, MSH2, PMS1, SEC23B, BLM, ATR, BAP1, BBC3, CDKN1A, FAM175A, FANCA, FANCC, FANCI, FANCL, FANCM, GEN1, RAD51B, RBBP8, RECQL, RINT1, TP53BP1, XRCC1, XRCC3). Samples were sequenced using the Illumina MiSeq platform multiplexed for 100X mean depth of coverage. Intronic or synonymous exonic variants and those with &amp;lt;40 reads, or alternative allele frequency &amp;gt;3% in African populations in the 1000 Genomes, ExAC, or NHLBI ESP6500SI databases were filtered. Only variants in known BCS genes could be considered definitively pathogenic (DP), defined as missense variants categorized as pathogenic in ClinVar and all frameshift, nonsense, and splice site variants. All other variants were defined as variants of uncertain significance (VUS). We identified 54 women harboring DP mutations in 15 known BCS genes. Mutations in BRCA1/2 accounted for 32% of all DP mutations. Notably, nearly 17% of DP mutations were in MSH6, a gene only recently described as associated with increased risk of BCA in the general population. Among women with these DP mutations, nearly 25% had no high-risk characteristics. Ten VUS in known BCS genes were identified, where 4 were reported in ClinVar (BARD1, RAD5C, BRCA2, PMS2) and 6 were novel (PMS2, BRCA1, MUTYH, MSH6, NBN, MRE11). Among the candidate BCS genes, 63 VUS were identified: 51 frameshift variants, 5 nonsense variants, 3 splice site variants, and 4 missense mutations predicted to be pathogenic by ≥8/9 algorithms. Nearly 60% of participants had neither a DP mutation or VUS. These data suggest that AAW with BCA have a unique mutation spectrum and may benefit from BCS gene sequencing regardless of family history, age, or subtype. Additional sequencing in AAW will lay the foundation for identification of germline factors associated with BCA risk and prognosis specifically in AAW and offer opportunities for personalized risk assessment. Citation Format: Kristen Purrington, Gregory Dyson, Douglas Craig, Julie Boerner, Julie Madden, Jennifer Beebe-Dimmer, Ann G. Schwartz, Michael Simon. Spectrum of heritable mutations in 43 known and candidate breast cancer susceptibility genes in African American women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4175.

Factors Influencing Breast Cancer Genetic Testing Among High Risk African American Women: A Systematic Review

African American women are disproportionately impacted by breast cancer and its associated effects. They have the highest breast cancer mortality rate of all racial and ethnic groups in the U.S., yet, many high risk African American women do not follow-up with genetic testing despite, having a shorter survival rate and more likely to develop malignancies or aggressive forms of breast cancer than white women. Purpose: This review explored breast cancer genetic follow up and barriers among African American women and made recommendations for designing tailored high risk breast cancer programs. Method: The Integrative Model of Behavioral Prediction framework provided the framework for the review. PubMed, PSYINFO, CINAHL and Cochrane Collection Plus databases were searched for articles published from 2007 to 2017 that focused on attitude and beliefs that influenced genetic testing follow up among African American women. Three reviewers independently reviewed and appraised articles. The quality of the articles was assessed to determine the evidence level and overall recommendations using the Joanna Bridge Institute grading criteria. Results: Sixteen of the 2275 articles reviewed met the inclusion criteria of which, seven showed statistically significance changes related to family concerns, medical mistrust and cost barriers; decreases in breast cancer worry and perceived risk after genetic counseling; and higher education level and diagnosed early increased genetic testing. Conclusions: This systematic review provides greater understanding of how the social determinants of health influence decisions about genetic testing and treatment to determine why African American women who are at risk for breast cancer, do not progress to genetic testing. It provided recommendations for designing sensitive curriculum content for African American women and providers to increase genetic follow-up and reduce breast cancer disparity. The results of this review could be used to design comprehensive, tailored interventions to address the identified barriers, increase breast cancer awareness and early detection, and help minority women make informed, value decisions about genetic testing and treatment options. Recommendations: Future research is required to examine the role communities, agencies and policy makers play in improving clinical outcomes for minorities.

Layers of information: interacting constraints on breast cancer risk-management by high-risk African American women

ABSTRACT Objectives: To understand how various decision-making dynamics interact to shape the risk-management choices of African American women at high-risk of breast cancer, and to explore whether African American and White women have differential access to the information and interactions that promote proactive, confident risk-management behavior. Design: This paper draws on 50 original in-depth, semi-structured interviews with African American and White women at elevated risk of breast cancer. We used inductive grounded-theory methodology to explore the processes by which women make risk-management decisions and to compare those processes between racial groups. Moving backward from women’s decisions about whether or not to engage in specific risk-management behaviors, we explored the patterns that underlie behavioral decisions. Results: We find that decisions to engage in risk-management behavior rest on three accumulated layers of information. The layer most proximal to making risk-management decisions involves specific information about risk-management options; the middle layer involves general information about managing breast cancer risk; and the foundational layer involves personal perceptions of breast cancer risk and prevention. African American and White women experience distinct dynamics at each of these levels, and these differences may help explain racial differences in risk-management behavior. Compared to their White counterparts, African American women faced additional burdens at every step along the risk-management journey. Conclusion: These findings suggest that information gathering is more complex than has previously been addressed, that information access and provider access are closely related, and that African American women may be systematically disadvantaged with respect to information-generating experiences. Preventing cancer morbidity and mortality requires that all high-risk women have access to the layers of information necessary to engage in cancer screenings and preventive interventions. These results exemplify the ways that structural, social, and interpersonal inequalities combine to influence risk-management choices.

Abstract A52: Racial Differences in Prevention Decision Making among Women at High Risk of Breast Cancer

Abstract Background &amp; Objectives: Prior research has documented significant racial disparities in adherence to breast cancer screening recommendations, use of breast-conserving surgery by early stage breast cancer patients, and breast cancer mortality. Decision making about breast cancer prevention options among high risk women has been less thoroughly studied, and racial differences remain mostly unexplored in this arena. The current study employs semi-structured interviews and inductive analytic methods to explore prevention decision making among African American and White women. Its core objective is to investigate the degree to which decision-making processes and outcomes differ across racial groups, and the specific content of these differences, in order to support interventions and programs to facilitate empowered, preventive decision making. Methods: In-depth, semi-structured interviews were conducted with 20 African American and 30 non-Hispanic White women at elevated risk of breast cancer. Allowing women to speak in their own words, these interviews explore women's perception of their risk status; the sources and content of risk information they have obtained; their understanding and consideration of prevention options; decision-making processes; decision-making networks, psychosocial well-being; and women's use of financial, time, and energy resources in coping with risk and prevention. Interviews ranged in length from 30 to 140 minutes and were professionally transcribed. Transcribed data are analyzed through grounded theory methods, using the NVivo 10 software package for qualitative data. Results: High risk African American women's experiences are distinct from those of their White counterparts in a range of ways, including the following. (1) African American women are much less frequently aware of the existence of prophylactic surgeries and chemoprevention options are clinically recommended for women at their own level of risk. (2) Among women who do know about these prevention options, African American women are less likely to consider or undertake prophylactic surgeries or chemoprevention to lower their breast cancer risk. (3) A much higher proportion of African American women have experienced several different types of cancer among their loved ones. These women tend to perceive of themselves as at risk for cancer in general, and not to perceive a specific high risk for breast or ovarian cancer. (4) African American women experience considerably more financial limitations on their ability to access health care and engage in specific prevention activities. Most have been uninsured for some period, and have had at least one health care decision affected by financial constraints. (5) African American women are considerably more likely to reference faith, spirituality, and religion in discussing their perceived risk of cancer and their attitudes toward prevention behavior. Conclusions &amp; Implications: High risk women's narratives reveal substantial racial differences in perceptions, feelings, and choices related to breast cancer prevention. African American women who are clinically determined to be at high risk for breast and ovarian cancer are less likely than similar White women to understand this specific risk, to know about prevention options that could lower the risk, or to consider using these options even when they do know about them. The processes through which African American women navigate risk and prevention are also more heavily influenced by religious faith and financial constraint than those of White women. These distinctions merit further investigation, and confirmation with larger samples. Ultimately, knowledge of such inter-group differences may contribute to tailored interventions to support empowered and health-protective decision making among women at elevated risk. Citation Format: Tasleem J. Padamsee, Anna Muraveva, Electra D. Paskett. Racial Differences in Prevention Decision Making among Women at High Risk of Breast Cancer. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A52.

A Systematic Review of DNA Methylation and Preterm Birth in African American Women.

The causes of many cases of preterm birth (PTB) remain enigmatic. Increased understanding of how epigenetic factors are associated with health outcomes has resulted in studies examining DNA methylation (DNAm) as a contributing factor to PTB. However, few studies on PTB and DNAm have included African American women, the group with the highest rate of PTB. The objective of this review was to systematically analyze the existing studies on DNAm and PTB among African American women. Studies ( N = 10) were limited by small sample size, cross-sectional study designs, inconsistent methodologies for epigenomic analysis, and evaluation of different tissue types across studies. African Americans comprised less than half of the sample in 50% of the studies reviewed. Despite these limitations, there is evidence for an association between DNAm patterns and PTB. Future research on DNAm patterns and PTB should use longitudinal study designs, repeated DNAm testing, and a clinically relevant definition of PTB and should include large samples of high-risk African American women to better understand the mechanisms for PTB in this population.

Abstract B52: Pilot study: Random periareolar fine needle aspiration (RPFNA) accurately depicts biochemical phenotype displayed in breast tissues of high risk African American women

Abstract Background: There are more than 2.9 million breast cancer survivors in America today. However African American women have a 79% five-year survival while survival rates for European American women are at 92%. While early detection increases the survivability rates of most breast cancer, the standard mammogram fails to identify the earlier stages of some of the more aggressive types of breast cancer. Short-term breast cancer risks in women are increasingly being identified by Random Periareolar Fine Needle Aspiration (RPFNA). While the reproducibility of this technique is no longer the primary concern for its usage; RPFNA's small sample-sets and the inability to accurately correlate pathological and biochemical findings within the entire breast inhibits full acceptance of this technique. The purpose of this study was to determine if the utilization RPFNA accurately sampled the entire breast tissue. Methods: In this pilot study 10 high risk African American women who were high risk for breast cancer (known or suspected BRCA1 mutation carriers) had breast tissues collect by RPFNA. These samples were laser captured and the RPFNA protein expression for wide array of biomarkers (stem cell, epithelial- mesenchymal transition (EMT), proliferation, apoptosis and senescence) were assessed utilizing reverse-phase protein microarray in mammary epithelial cells. The same 10 high risk African American women either underwent prophylactic mastectomies or had a mastectomy after cancer diagnosis. Mastectomy specimens were serial sliced into 2.5 centimeter slices and 2 to 3 cubic centimeter samples were excised from a specified section of each slice of breast tissue. On average 103 samples were collected from each breast and the same (RPFNA) biomarkers were analyzed. Results: In this exploratory study, we have determined there are no significant differences between the expression of the biomarkers we have tested in RPFNA samples and the whole breast tissue sampling. Specifically we have tested for EMT markers (Vimentin and Snail), p53 and additional markers involved in proliferation and apoptosis. Conclusions: This study shows that RPFNA is an accurate measure of mammary breast epithelial and this technique directly correlates to the measurements found throughout the entire breast tissues. RPFNA did not show any significant differences in the expression of specific biomarkers tested, suggesting that RPFNA samples could be utilized to develop more robust breast cancer risk profiles. Citation Format: Christopher Sistrunk, Adrian Ambrose, Amira Carter, Victoria Seewaldt. Pilot study: Random periareolar fine needle aspiration (RPFNA) accurately depicts biochemical phenotype displayed in breast tissues of high risk African American women. [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 B52.

Inflammation and Cardiometabolic Risk in African American Women Is Reduced by a Pilot Community-Based Educational Intervention.

Cardiovascular disease (CVD) is the leading cause of death for women, and African Americans have higher rates of CVD mortality than do other racio/ethnic groups. Women in community settings can benefit from preventive interventions, yet few investigations of successful programs have been conducted and evaluated in high-risk women, especially for metabolic syndrome. The purpose of our study was to pilot and assess the effectiveness of a 4-month pre-/post-CVD preventive educational intervention in improving knowledge, clinical risk profiles, adoption of heart-healthy lifestyles, inflammatory burden, and cardiometabolic risk in African American women in local communities. Forty-two African American women (mean age 59 years) enrolled in the 4-month educational Cardiovascular Disease Preventive Intervention Program in Sacramento, CA, in 2010. Participants completed knowledge-based surveys pre-/postintervention, provided clinical measures (weight, waist circumference, body mass index (BMI), blood pressure and blood samples for analysis of fasting glucose and lipids, and inflammatory markers: tumor necrosis factor (TNF)-α±, high-sensitivity C-reactive protein (hs-CRP), and interleukin (IL)-12. The CVD risk profile of participants confirmed a high-risk cohort. Postintervention (n=31), there were significant (p<0.05) gains in knowledge for all symptoms of a heart attack and calling 911; improvements in clinical risk parameters, especially for waist circumference and low-density lipoprotein (LDL) cholesterol (p<0.05); and reductions in all the inflammatory markers assessed: TNF-α±by 16%, IL-12 by 20%, and hs-CRP by 26% (p<0.05). There was also a 60% reduction in the number of participants with metabolic syndrome (MetS) (p<0.05), driven primarily by reductions in triglycerides and glucose and a rise in high-density lipoprotein (HDL) cholesterol. We demonstrated the efficacy of a pilot community-based educational cardiovascular program in reducing cardiometabolic risk and inflammation in high-risk African American women. Our successful culturally appropriate and sustainable model could be implemented as part of comprehensive efforts to improve community-based health outcomes.

Abstract 28: Chemoprevention strategies to target abnormal imprinting in high-risk African American women who do or do not carry a BRCA1 mutation

Abstract Background: Genomic imprinting is an inherited form of parent-of-origin-specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. KCNK9 encodes TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. KCNK9 gene amplification accounts for increased expression in &amp;lt;10% of these breast cancers. Methods/Results: Here we show that KCNK9 has imprinted expression in breast tissue and provide the first identification of the KCNK9 DMR and DMR-associated open chromatin. Our studies show that loss of KCNK9 regulatory methylation and imprinted expression occurs in 75% of triple-negative breast cancer (TNBC) and loss of methylation occurs in non-cancerous tissue from high-risk women. Functional studies show that TASK3 protein regulates mitochondrial membrane potential and apoptosis-sensitivity. In live TNBC cells and non-cancerous mammary epithelial cells from high-risk women, loss of KCNK9 DMR methylation predicts increased mitochondrial membrane potential (p=0.007). African American women have a significantly higher frequency of loss of KCNK9 imprinting than do risk-matched Caucasian women (p=0.005). African American women with BRCA1 mutation have the highest frequency of loss (p&amp;lt;0.0001). Clinical Prevention: This is the first identification of the KCNK9 DMR and demonstration that loss of methylation and overexpression of TASK3 increases mitochondrial membrane potential and promotes apoptosis resistance. Low-toxicity inhibitors of TASK3 are in clinical use and can be readily re-purposed to provide cost effective chemoprevention. These inhibitors include K+ inhibitors (developed for cardiac indications) and Schwann Pepper. Our studies identify TASK3 as a “drugable”, low-toxicity target that can be readily employed as a novel target for prevention and treatment of TNBC, particularly in high-risk African American women. Citation Format: Victoria Seewaldt, David Skaar, Eric Dietze, Shraddha Desai, Randy Jirtle. Chemoprevention strategies to target abnormal imprinting in high-risk African American women who do or do not carry a BRCA1 mutation. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 28. doi:10.1158/1538-7445.CANSUSC14-28

Abstract A46: Breast cancers come out of nowhere: A two part Durham Community/Duke partnership to identify signaling pathways during the initiation of triple-negative breast cancer in African American women

Abstract Background: The current trend of increased survivability of women with breast cancer has been linked to increased awareness, early detection and better treatment. In fact the American Cancer Society estimate that there are more than 2.5 million breast cancer survivors living in America today. However the trends of these overall numbers are expressed quiet differently in the African American community. African American women have a 77% five-year survival rate while survival rates for European American are at 90%. It is clear that lack of access plays a role in poor survival of African American women. Other factors are hypothesized to be aggressive biology and lack of early detection strategies for triple-negative breast cancer. Methods and Results: Phase I: We developed a community outreach partnership with the African American community in Durham, NC. One of the concerns of the community was that aggressive breast cancers “appeared to come out of nowhere” and seemed to defy the conventional model of stepwise breast cancer progression. This alliance allowed the development of a partnership to use breast Magnetic Resonance Imaging (MRI) screening to evaluate the onset of breast cancer occurring in over 300 African American high-risk women (&amp;gt;48 month observation, 12 cancers). The results of this study corroborated the concerns of the community, that incidence of breast cancer could indeed occur in less than 6 months in women who had previously had a normal MRI. The results suggested that these aggressive breast cancers displayed an accelerated initiation and development within the patients of the local African American community, validating community observations. Phase II: The second concern raised by our community partners was the lack of prevention agents for these aggressive breast cancers. In partnership with Durham community members, our current study investigated signaling pathways activated during the initiation of triple-negative breast cancer in African American women. For our study 10 African American women who were at highest risk for breast cancer (either known or suspected BRCA1 mutation carriers) donated mastectomy tissue. Women either underwent prophylactic mastectomy or had mastectomy after a cancer diagnosis. Donated mastectomy specimens were serial sliced into 2.5 centimeter slices and 2 to 3 cubic centimeter samples were excised from specified section of each slice of breast tissue. Breast tissues were snap frozen, formalin-fixed and OCT embedded to preserve samples for further analysis. Thus far tissue tensile forces, collagen composition, metabolic and proteomic profiles have been characterized for this cohort. In addition biomarkers for stem cell, proliferation, apoptosis and senescence have been established. Conclusion: Our Durham Community/Duke Partnership has allowed us to study a unique phenotype displayed in pre- malignant breast lesion found in rapid onset breast cancers displayed in high-risk African American women. Our study highlights the power of investigators working in collaboration and partnership with the community. Citation Format: Christopher Sistrunk, Stephaine Robertson, Adrian Ambrose, Catherine Ibarra Drendall, Victoria Seewaldt. Breast cancers come out of nowhere: A two part Durham Community/Duke partnership to identify signaling pathways during the initiation of triple-negative breast cancer in African American women. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr A46. doi:10.1158/1538-7755.DISP13-A46

Abstract C65: Loss of imprinting of KCNK9 in African American women with triple-negative breast cancer

Abstract Background: It has been long suspected that prenatal nutrition and environmental toxins play a role in promoting breast cancer. Genomic imprinting is an inherited form of parent-of-origin-specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. Recent studies show that exposure to the environmental plastic bis-phenol A and vitamin D deficiencies promote loss of normal imprinting. African American (AA) women are known to have vitamin D deficiency at a significantly higher frequency than women of Northern European descent. Here we investigated a mechanism that may explain the higher rate of aggressive triple-negative breast cancers (TNBC) in AA women. Methods and Results: KCNK9 encodes TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. Our studies have identified a differentially methylated region (DMR) for KCNK9 and shown monoallelic expression of KCNK9 in breast tissue. Using patient samples, we show loss of imprinted expression in tumor cells, loss of KCNK9 regulatory methylation in 75% of TNBC samples, and loss of methylation in non-cancerous tissue from high-risk AA women. In live TNBC cells and non-cancerous mammary epithelial cells from high-risk women, loss of KCNK9 DMR methylation correlates with increased mitochondrial membrane potential. Significance: This is the first identification of the KCNK9 DMR and demonstration that loss of methylation and overexpression of TASK3 increases mitochondrial membrane potential and promotes apoptosis resistance. These novel findings regarding KCNK9 loss of methylation and its disruption in a subset of tumors may lead to new approaches in diagnosis and targeted therapy of breast cancer. Citation Format: Shraddha Desai, David Skaar, Eric Dietze, Adrian Ambrose, Randy Jirtle, Victoria Seewaldt. Loss of imprinting of KCNK9 in African American women with triple-negative breast cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C65. doi:10.1158/1538-7755.DISP13-C65

Likelihood of Emergency Contraception Use Among African-American Women at Risk of Adverse Birth Outcomes

Nearly a half million infants in the United States are born preterm or with low birth weight each year. Providing women who have had a prior adverse birth outcome with access to family planning can help reduce the incidence of subsequent high-risk pregnancies and adverse outcomes. One effective option to prevent unintended pregnancy for women with a prior adverse birth outcome who either do not use contraception consistently or whose contraception fails is emergency contraception (EC). The purpose of our study was to understand willingness to use EC among African-American women who recently had an adverse birth outcome. The Healthy Births Healthy Communities (HBHC) Interconceptional Care Project (ICCP) targeted high-risk African-American women from two low-income Chicago neighborhoods who recently had an adverse birth outcome. The aim of HBHC ICCP was to improve participants' future birth outcomes by providing medical and social services and helping women to clarify their reproductive life goals. Information about participants' pregnancy intentions and willingness to use EC was measured in an interview shortly after enrollment into the study. Over 90% of the 131 women in our study either did not want to become pregnant or did not know if they wanted to become pregnant within the next 2 years. These women had 4.4 times higher odds of reporting willingness to use EC as compared to women who reported a desire to become pregnant within the next 2 years (75.6 vs. 50.0%, respectively; AOR: 4.4; 95% CI 1.1, 17.6). EC is an essential part of the reproductive toolkit for women at high risk of adverse birth outcomes who are not intending pregnancy, along with reproductive life planning and use of effective contraception.

Intimate partner violence during pregnancy: victim or perpetrator? Does it make a difference?

To differentiate between forms of intimate partner violence (IPV) (victim only, perpetrator only, or participating in reciprocal violence) and examine risk profiles and pregnancy outcomes. Prospective. Washington, DC, July 2001 to October 2003. A total of 1044 high-risk African-American pregnant women who participated in a randomised controlled trial to address IPV, depression, smoking and environmental tobacco smoke exposure. Multivariable linear and logistic regression. Low and very low birthweight, preterm and very preterm birth. Five percent of women were victims only, 12% were perpetrators only, 27% participated in reciprocal violence and 55% reported no IPV. Women reporting reciprocal violence in the past year were more likely to drink, use illicit drugs and experience environmental tobacco smoke exposure and were less likely to be very happy about their pregnancies. Women reporting any type of IPV were more likely to be depressed than those reporting no IPV. Women experiencing reciprocal violence reported the highest levels of depression. Women who were victims of IPV were more likely to give birth prematurely and deliver low-birthweight and very-low-birthweight infants. We conclude that women were at highest risk for pregnancy risk factors when they participated in reciprocal violence and so might be at higher risk for long-term consequences, but women who were victims of IPV were more likely to show proximal negative outcomes like preterm birth and low birthweight infants. Different types of interventions may be needed for these two forms of IPV.

Abstract P1-03-01: Evidence for the Warburg effect in mammary atypia from high-risk African American women.

Abstract Background: Aggressive cancers are known to consume glucose avidly and produce lactic acid (rather than fully metabolize glucose via the Tricarboxylic Acid (TCA) cycle). This shift toward lactate production, even in the presence of adequate oxygen, is termed the Warburg effect. The Warburg effect is thought to be a late event in breast cancer, however, our studies in high-risk women provide evidence that the Warburg effect occurs during cancer initiation. This is an important observation as glucose-signaling can be readily targeted for breast cancer prevention with minimal toxicity. Here we investigated the role of the Warburg effect in breast cancer initiation in young high-risk women. Methods and Results: Similar to fluorodeoxyglucose, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) is a fluorescent glucose analog that can be used to track glucose uptake and glycolysis. 2-NBDG spectroscopy provides a means to track glucose metabolism in live mammary epithelial cells from high-risk women. We used 2-NBDG spectroscopy to measure glucose uptake in ER− breast cancer and live atypical mammary epithelial cells from high-risk premenopausal women. We observe that both triple-negative breast cancer and a subset of atypia exhibits accumulation of 2-NBDG. There is growing recognition that phosphoprotein signaling networks (rather than single genes) play a key role in breast cancer initiation and progression. Our team used Reverse Phase Proteomic Microarray (RPPM) profiling to test for activation of phosphoprotein signaling networks in atypical RPFNA cytology from high-risk premenopausal women in our cohort. RPFNA were obtained from two independent sets of 39 and 38 high-risk premenopausal women; 45% of these women were African American. The signaling network most highly expressed in precancerous cells contained activated signaling proteins associated with the Warburg effect (AKT/mTOR/PI3K), insulin signaling (pACC, IRS1) and epithelial to mesenchymal transition (EMT) IL6/Stat3/vimentin. Conclusions: This is the first evidence that abnormal glucose uptake and the Warburg effect occurs during breast cancer initiation in high-risk premenopausal women. These studies demonstrate our ability to identify abnormal glucose and activated signaling networks associated with the Warbug effect in atypical mammary cells from high-risk women. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-03-01.

Factors associated with psychological distress among women of African descent at high risk for BRCA mutations.

Little is known about psychological distress among women of African descent who are at high risk for a BRCA mutation. This is a group for whom breast cancer risk reduction is critical due to the group's high rates of breast cancer mortality. Distress is important to consider as it may reduce the potential benefit of genetic counseling and negatively affect decision making related to risk reduction. The goals of the current study were to examine breast cancer-specific distress and depressive symptoms in women of African descent at who are at high risk for a BRCA mutation and to identify background factors associated with these outcomes. Participants were 148 high-risk African American and Caribbean women who were part of a larger study that offered participants BRCA counseling at no cost. Participants completed the Impact of Events Scale, which assessed breast cancer-specific distress, and the Center of Epidemiological Studies-Depression Scale, which assessed depressive symptoms. Results of analyses revealed that almost half of the sample achieved scores indicating high and clinically significant breast cancer-specific distress, while almost one-third had clinically significant depression scores. Results further showed that low income was significantly associated with cancer-specific distress, while having a cancer diagnosis was significantly associated with depressive symptoms. These results underscore the need for targeted psychological support throughout the genetic risk assessment process for this particular high-risk group.

Abstract CN07-03: IL6 and AKT as targets for chemoprevention

Abstract Background: Currently we lack adequate prevention strategies for triple-negative breast cancer; progress in designing targeted strategies is limited by a lack of knowledge of the biology of cancer initiation. The origins of triple-negative breast cancer in premenopausal women are poorly understood. Importantly, we do not understand whether the molecular pathways that underlie the aggressive behavior of triple-negative breast cancer can be detected in premalignant breast lesions. Growing evidence indicates that early mammary carcinogenesis is regulated by integrated signaling networks and not by isolated genes. Interleukin-6 (IL6) plays a role in stem cell regeneration, promotes epithelial to mesenchymal transition (EMT), and high IL6 serum levels predict a poor outcome in premenopausal women with triple-negative breast cancer. Methods and Results: We used Reverse-Phase Protein Microarray (RPPM) profiling to test for activation of phosphoprotein signaling in premalignant Random Periareolar Fine Needle Aspiration (RPFNA) mammary epithelial cytology from 65 high-risk African American women. Unsupervised hierarchical clustering of RPPM proteomic analysis RPFNA aspirates identified three activated ER− signaling pathways including co-activation of Akt/mTOR/PI3K and IL6/pStat3/vimentin. Analysis of interstitial breast tissue demonstrated that high interstitial IL6/VEGF cytokine production predicted high epithelial expression of pStat3/vimentin. Based on these observations we are currently launching a prevention trial to target Akt/mTor using metformin 500 mg bid. Conclusion: This is the first demonstration that Akt/mTor and IL6/Stat3/vimentin signaling is activated in pre-cancerous mammary epithelial cells from high-risk premenopausal women. Currently we are testing whether trials are on-going to test whether metformin can inhibit activation of mammary epithelial Akt/mTor and perhaps IL6/Stat3/vimentin signaling. Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN07-03.