Teaching & Learning Guide for: The Changing Significance of Race: African Americans and the Hebrew Bible

Background. There is evidence to suggest that early life exposures including birthweight, history of having been breastfed during infancy, in utero exposure to maternal smoking, and parental education are associated with BC risk. Potential underlying mechanisms include variability in exposure to maternal endogenous sex and growth hormones. Also, parental socioeconomic status may be a proxy for environmental characteristics that impact biological processes in early life, and ultimately influence BC risk. Research has focused on EA women; relatively little is known about associations between early life exposures and BC risk for AA women. Methods. We conducted a case-control study in AA and EA women aged 22-75 years living in metropolitan New York City and eastern New Jersey (Women's Circle of Health Study). Breast cancer cases (AA n=827; EA n=772) were diagnosed with primary, incident, histologically confirmed invasive BC or ductal carcinoma in situ. Controls (AA n=905; EA n=715) were frequency matched to cases on age and race. Birthweight, history of having been breastfed during infancy, history of in utero exposure to maternal smoking, and parental education were by self-report using an interviewer-administered questionnaire. Results. Birthweight was not significantly associated with BC risk in this study for AA or EA women. Having been breastfed during infancy was associated with significantly increased BC risk for both groups (ORAA=1.60, 95% Cl: 1.27-2.02; OREA=1.45, 95% Cl: 1.14-1.85). For EA women, but not AA women, reporting in utero exposure to maternal smoking was associated with significantly decreased BC risk (OR=0.61, 95% Cl: 0.45-0.82). Among AA women, those born to mothers with at least a college degree had a significantly lower BC risk compared to AA women born to mothers with a high school or less education (OR=0.67, 95% Cl: 0.49-0.93). Among EA women, we found no association with maternal education. However, EA women born to fathers with at least a college degree had a significantly lower BC risk compared to EA women born to fathers with a high school or less education (OR=0.65, 95% Cl: 0.51-0.84). Conclusions. Our findings support the hypothesis that early life exposures impact adult BC risk. History of having been breastfed during infancy, in utero exposure to maternal smoking, and parental education were all associated with BC risk. While minor differences in risk estimates were found between EA and AA women, associations were similar. Citation Format: Mark L. Glasgow, Jo Freudenheim, Gary Zirpoli, Elisa Bandera, Christine Ambrosone. Early life exposures and breast cancer (BC) risk among African American (AA) and European American (EA) women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-13. doi:10.1158/1538-7445.AM2013-LB-13

Screening mammography is associated with early detection of breast cancer (BC) and reduced BC mortality. To understand factors that influence screening mammography receipt in minority women with unrecognized risk factors for BC, this study examined BC screening behaviors among women with BC. Due to the BC survival disparities observed in African American (AA) and Mexican American (MA) women compared to whites, AA and MA women living in Texas and Arizona who were participants of the ELLA Binational Breast Cancer Study were selected for this study based on a diagnosis of BC. Data on socioeconomic status (SES), reproductive history, family history, insurance status, acculturation, and breast health history were collected via questionnaires and medical record abstraction. 601 women aged 40 years or older at time of BC diagnosis were included in this study, including 270 AA, 151 MA women classified as high-acculturation (MA-HA) and 180 MA women classified as low-acculturation (MA-LA). Logistic regression analysis was used to assess differences in mammography receipt in the last five years prior to BC diagnosis stratified by race/ethnicity and acculturation and for all groups combined. MA women in this study suffer a larger disparity than AA women with regards to screening mammography. Despite high rates of screening mammography among AA and MA women, 62% of BC was self-detected in the study population. AA women (OR=1.0) and MA-HA (OR=0.91; 95% CI: 0.57-1.48) women were more than twice as likely to receive screening mammography compared to MA-LA (OR=0.38; 95% CI: 0.25-0.59), adjusted for age. After adjusting for age, education, and insurance, there was no significant difference in screening mammography receipt between these three groups. Women who had a known family history of BC were more than twice as likely to receive screening mammography than women who had unknown or no family history (OR=2.02; 95% CI: 1.19-3.55). However, although AA and MA-HA women were twice as likely as MA-LA to report a family history of BC (20% vs. 23% vs. 12%, respectively), recognized family history did not account for the differences in screening mammography use between these groups. Thus, the differences observed in screening mammography receipt by race/ethnicity and acculturation among AA, MA-HA, and MA-LA are likely explained by SES variables, including education and insurance. Due to the large proportion of AA and MA women who reported self-detecting their BC, women must be educated about the importance of breast awareness and prompt reporting of findings to a health professional after noticing breast changes. In addition, cancer screening programs targeting underserved women should provide culturally appropriate messages about the importance of knowing their family history and the benefits of screening mammography. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2806.

IA19: Elucidating the origins of aggressive breast cancer in African American women

Background: Human endogenous retroviruses (HERVs) are remnants of ancient virus infection. The majority of them are disabled due to mutation and/or deletion. However, HERV K113 and K115 have been shown to have full-length insertion in human genome and retain the ability to encode functional virus proteins in some individuals. Considering the potential role of HERVs in carcinogenesis and a high genetic homology between HERV K and mouse mammary tumor virus, the study is designed to investigate the distribution of HERV K113 and K115 in African American (AA) and European American (EA) women, and their association with breast cancer risk. Methods: Built on a funded multi-center case-control study, the Women's Circle of Health Study, the study included 1242 cases (608 AA and 634 EA) and 1422 controls (783 AA and 639 EA). PCR followed by fragment analysis was used for insertional polymorphism assay. For each HERV, three PCRs were performed to determine whether the insertion is partial or full length. Indeed, a subset of individuals showed insertion of long terminal repeat (LTR) of HERV, instead of whole virus insertion. The distribution of insertional polymorphisms was compared between AA and EA as well as between cases and controls. Logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI) with adjustment for age at diagnosis and proportion of European ancestry. Results: For both K113 and K115, with or without including LTR insertion, the distribution was significantly different between AA and EA women. A two-fold higher prevalence of HERVs was observed in AA women, showing 51.5% of individuals with at least one copy of either K113 or K115 compared to 23.3% in EA women among controls. The prevalence of HERVs was inversely associated with proportions of European ancestry, showing a decrease from averagely 66% European ancestry in individuals without insertion to 42.9%, 23.2%, 13.3% with one, two, or more insertions of HERV K113 or K115, respectively. Between cases and controls, the prevalence of K113 was slightly higher in controls, but not for K115. Furthermore, both K113 and K115 insertion were significantly associated with the reduced risk of breast cancer in both AA and EA women. Near 50% reduction of breast cancer risk was observed in AA and EA women with homozygous insertion of K113 (combined OR, 0.45; 95% CI, 0.25-0.80). A trend of a reduction in breast cancer risk with an increase of copy number of HERV K insertion was observed in both AA and EA women. However, there was no association with breast cancer subtypes. Conclusion: This is the first study to document the prevalence of HERV K113 and K115 in AA and EA population, and to report an inverse association with breast cancer risk. Validation of the findings in a relatively large study is warranted in the future. Funded by 5R03CA156645, K07CA148888, P01151135, and R01CA100598. Citation Format: Li Tang, Steven R. Gregory, David Tritchler, Gary R. Zirpoli, Song Yao, Warren Davis, Gregory L. Ciupak, Yasmin Thanavala, Elisa V. Bandera, Christine B. Ambrosone. Associations between insertional polymorphisms of human endogenous retrovirus K113 and K115 and breast cancer risk in African American and European American women. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2789. doi:10.1158/1538-7445.AM2015-2789

Evidence exists that increased levels of physical activity decrease the population burden of cardiovascular disease (CVD). Although risk factors for CVD, including plasma lipids and lipoproteins, have been associated with physical activity, studies including a sizeable number of minority participants are lacking. Our purpose was to interrogate the longitudinal effect of physical activity on plasma lipids and lipoproteins in the African American and white participants of the Atherosclerosis Risk in Communities (ARIC) Study. Nine years of follow-up data on 8,764 individuals aged 45-64 years at baseline were used in linear mixed-effects models to estimate the association between increases in baseline physical activity on mean change in HDL, LDL, total cholesterol, and triglyceride levels. Increases in the level of activity were associated with increases in HDL in all strata and decreases in triglycerides among white participants. Physical activity was associated with LDL in all women, while the association with total cholesterol was limited to African American women. This study is one of the few to investigate the effect of physical activity on lipids and lipoproteins in a race- and sex-specific manner. Overall our results highlight the importance of physical activity on plasma lipid profiles and provide evidence for novel differential associations.

Research indicates that African American women experience especially high rates of intimate partner violence (IPV). Unique contributing factors, such as experiences of racism, compound the experience of IPV for African American women. This complex web of victimization is associated with a host of significant mental and physical health consequences, social and economic consequences, and increased engagement in high-risk behaviors for these women. African American women’s help-seeking efforts are hindered by a diverse set of circumstances. In addition, the picture of the African American community has changed significantly in recent decades. The growing diversity of the “African American” community in the U.S. implores us to enhance our understanding of the unique sub-populations of Black women in America (African Americans, African immigrants and refugees, African Caribbean immigrants, African American lesbian, bisexual, and transgender women) to better meet their needs, and ultimately reduce IPV within the African American community. Despite over two decades of growth in the research and literature on IPV in the African American community, many sub-populations remain neglected. This paper aims to present a brief overview of the current state of the literature regarding the experience of IPV for African American female survivors and identify areas for further research.

In the United States, obesity prevalence has been increasing steadily over the years in all racial/ethnic groups, but is markedly higher in African American (AA) (57.2%) and Hispanic women (46.9%), compared to non-Hispanic white (NHW) (38.2%) and NH Asian (12.4%) women (1). Obesity has been shown to affect cancer risk and progression and can also play a role on disease presentation, treatment efficacy and toxicity, and complicate clinical management of cancer due to obesity-related comorbidities such as hypertension and diabetes (2). Given the high prevalence of obesity in African American and Hispanic women and different metabolic consequences, understanding how it influences cancer risk, detection, disease presentation, clinical management, and progression and possible differences by race/ethnicity is crucial. Breast cancer is the most common cancer among women worldwide, with wide variation in incidence and mortality across geographic regions. In the US, incidence rates have been historically higher in NHW women, but AA and Hispanic women tend to develop the disease at an earlier age and with more aggressive features. In particular, they are more likely to get ER- and triple-negative (TN) tumors, which are more difficult to treat and have worse prognosis. More recent data show that incidence rates in NHW and AA women converged in 2012 due to an increase in incidence in AA women and relatively stable incidence in NHW women3. Death rates are higher in AA than in NHW women, and this mortality difference has been widening over time. Causes of these disparities in risk and survival are likely to be multifactorial, and obesity has been implicated. There is strong evidence, mostly from studies conducted in NHW women, that obesity and weight gain during adulthood are associated with increased risk of postmenopausal breast cancer, particularly among women not using menopausal hormone therapy (4). Obesity during adolescence and young adulthood has been associated with reduced breast cancer risk (4). There is also growing evidence that the association differs by hormone receptor subtype, and that what we have historically known for the association of obesity and breast cancer only applies to ER+ tumors. Few studies have evaluated the association of obesity with the risk of ER- and TN breast cancer and the evidence is inconsistent. In the AMBER Consortium (5), which included four studies in AA women, we found that for ER+ breast cancer, obesity reduced risk for premenopausal women and increased risk for postmenopausal women. However, the risk of TN breast cancer was reduced for postmenopausal women with high BMI, but elevated for those with a high waist-to-hip ratio. One possible explanation for these findings is that TN tumors may be more influenced by components of the metabolic syndrome (central obesity, insulin resistance, dyslipidemia, hypertension) than by estrogens, as suggested by others (6). While more limited, there is growing evidence that obesity is associated with worse breast cancer outcomes, particularly for HR+ tumors (7), with no conclusive evidence on differences by race/ethnicity. Ovarian cancer is the most lethal gynecologic cancer. With difficulties in early detection due to vague symptoms and the lack of effective screening tools, 60% of ovarian malignancies are detected when the disease is already at distant stage when 5-year survival is only 29% (8). Compared to NHW, incidence is lower in AA and Hispanic women, but survival is worse in both groups, after adjusting for age and stage (9) comparable to the incidence and mortality differences observed for breast cancer. Little is known about how the epidemiology of ovarian cancer may differ by race/ethnicity, but there is suggestive evidence that there may be differences in risk profiles, tumor subtype distribution, and clinical management, which may all be affected by obesity. For example, in KP ROCS (Kaiser Permanente Research on Ovarian Cancer Survival), a cohort study of ovarian cancer patients among Kaiser Permanente Northern California members, AA and Hispanic women were more likely to have chemotherapy dose reduction and unfavorable survival compared to NHW, after adjusting for clinical characteristics and detailed treatment information (10). Obesity was the most important predictor of chemotherapy dose reduction (11). There is a general misconception that obesity is not prevalent among ovarian cancer patients. In KP ROCS, 58.5% of AA and 40.7% of Hispanic ovarian cancer patients were obese at diagnosis, compared to 29.5% of NHW (10). Fewer than 1% of Hispanic women and none of the AA women were underweight at diagnosis. In AACES (African American Cancer Epidemiology Study), a multisite case-control study of ovarian cancer in AA women, 61.8% of the cases were obese approximately one year before diagnosis (12). There is growing evidence that obesity increases ovarian cancer risk (13), but most studies were conducted in NHW women. In AACES, we found elevated risk of ovarian cancer with higher BMI and weight gain during adulthood among AA postmenopausal women (12). The impact of body mass index (BMI) on ovarian cancer survival is less clear, but meta-analyses and pooled analyses have suggested that obesity before an ovarian cancer diagnosis might be associated with lower survival, with weaker evidence for BMI at diagnosis. In KP ROCS we found that the association of prediagnosis and at-diagnosis obesity with ovarian cancer varied by stage, with lower survival among obese women with localized disease and better survival among obese women with late-stage disease (14). We found no major differences by race/ethnicity in the impact of obesity on survival, but statistical power was limited as analyses included few AA and Hispanic women. Conclusion: There is growing evidence that higher body fatness is associated with increased breast and ovarian cancer risk and worse outcomes after diagnosis with these cancers, but there are multiple research gaps to fully understand these associations (15). Better methods are needed to measure adiposity, but tools also need to be feasible for use in population-based studies to allow the inclusion of large and multiethnic populations. The role of obesity on cancer risk and survival needs to be evaluated by tumor subtype, menopausal status, use of menopausal hormone therapy, and racial/ethnic subgroup with consideration of country of origin and genetic ancestry. The impact of body fatness during critical exposure windows and the impact of weight changes throughout the cancer continuum are also poorly understood. Cancer survival studies need to take into account prognostic factors, including chemotherapy dosing and obesity-related comorbidities that can have a direct impact on cancer clinical management and survival.

Background: African American (AA) women and patients with Triple Negative Breast Cancer (TNBC) have poor outcomes. It is unclear whether these worse outcomes in AA women are due to a higher frequency of TNBC in AA women. The purpose of our study was to determine difference in outcomes between AA and Caucasian (CA) female with TNBC. Methods: A retrospective study of women diagnosed with ER, PR and HER2 (1+) negative breast cancer between January 1/2001 and December 31/2013 at Vidant Medical Center (East Carolina University) in Greenville, North Carolina was undertaken. Patient demographics and tumor characteristics were analyzed to determine impact on overall survival. Results: In our institution, 4,434 women were diagnosed with breast cancer in this study period, of which 378 had TNBC. Our TNBC population was predominantly AA (53%). AA patients were younger (54.1 years vs 58.7 years, p=0.005), less often postmenopausal (62.6% vs 74.5%, p=0.013), more likely to have Medicaid (24.3% vs 7.9%, p <0.001), and to have received chemotherapy (80% vs 69%, p=0.017) compared to CA women. There was no difference in stage at diagnosis between AA and CA patients (p=0.12). By univariate analysis, improved survival in TNBC was associated with non-Medicaid status (p=0.01), early stage at diagnosis (p=0.001), N stage (<0.001), and tumor grade (p<0.001). A Cox regression analysis demonstrated that only insurance status (p=0.007) and N Stage (p=0.01) predicted outcomes in TNBC. Survival in TNBC was not affected by race (p=0.7). Conclusions: Poorer outcomes in AA women cannot be attributed to the higher frequency of TNBC. Improved access to healthcare, with broader insurance coverage, may help minimize disparities in outcome by diagnosing TNBC at an earlier stage.Background: African American (AA) women and patients with Triple Negative Breast Cancer (TNBC) have poor outcomes. It is unclear whether these worse outcomes in AA women are due to a higher frequency of TNBC in AA women. The purpose of our study was to determine difference in outcomes between AA and Caucasian (CA) female with TNBC. Methods: A retrospective study of women diagnosed with ER, PR and HER2 (1+) negative breast cancer between January 1/2001 and December 31/2013 at Vidant Medical Center (East Carolina University) in Greenville, North Carolina was undertaken. Patient demographics and tumor characteristics were analyzed to determine impact on overall survival. Results: In our institution, 4,434 women were diagnosed with breast cancer in this study period, of which 378 had TNBC. Our TNBC population was predominantly AA (53%). AA patients were younger (54.1 years vs 58.7 years, p=0.005), less often postmenopausal (62.6% vs 74.5%, p=0.013), more likely to have Medicaid (24.3% vs 7.9%, p <0.001), and to have received chemotherapy (80% vs 69%, p=0.017) compared to CA women. There was no difference in stage at diagnosis between AA and CA patients (p=0.12). By univariate analysis, improved survival in TNBC was associated with non-Medicaid status (p=0.01), early stage at diagnosis (p=0.001), N stage (<0.001), and tumor grade (p<0.001). A Cox regression analysis demonstrated that only insurance status (p=0.007) and N Stage (p=0.01) predicted outcomes in TNBC. Survival in TNBC was not affected by race (p=0.7). Conclusions: Poorer outcomes in AA women cannot be attributed to the higher frequency of TNBC. Improved access to healthcare, with broader insurance coverage, may help minimize disparities in outcome by diagnosing TNBC at an earlier stage. Citation Format: Mosquera C, Amin R, Wong JH. Effect of race on triple negative breast cancer outcomes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-26.

This essay examines the Iowa Federation of Colored Women's Clubs (IFCWC) campaign to operate a house for African American women at the University of Iowa from 1919 to 1950. (1) It seeks to add to a growing body of literature which focuses on African American philanthropy and collective black economic enterprises. An examination of the experiences of African American women at the University of Iowa and the IFCWC Home campaign offers an interesting case study that builds on recent research work on African American Women's philanthropy. (2) The IFCWC's economic enterprise developed because between 1913 and 1946, the University of Iowa barred African American students from campus and some student activities. The experiences of African American women at the University of Iowa are unique for two reasons: 1) the house they occupied was one of a few dormitories in the nation owned and operated by a formally organized group of African American women; and 2) the campaign to maintain the IFCWC Hom e provided mostly middle-class African American women students with the organizational, intellectual, and leadership skills necessary to become the next generation of black women activists. In general, the experiences of African American college women at predominantly white coeducational institutions in the early twentieth century are unique because white women often had the guidance and support of white women administrators and/or faculty. (3) African American women, on the other hand, had to look outside the university for such mentors and role models. The question remains then, how did the alliance with the IFCWC help to keep students connected to the African American community; and how did the community respond? How did limited employment prospects that resulted from race and gender prejudice help to bring about a sharply focused movement to make a college education available to a number of Iowa's young African American women? I contend that the IFCWC prepared African American women at the University of I owa to assume positions of leadership in organizations such as the IFCWC, National Association of Colored Women (NACW), the Order of the Eastern Star (OES), and the National Association for the Advancement of Colored People (NAACP), and a host of other local and regional civil rights organizations. (4) Upon graduation, these women also assumed responsibilities in their local communities in their effort to the race. This work places African American women's lives at the center of inquiry in a preexisting historiographical paradigm which often excludes them through a preoccupation with African American men and white women. A few scholars, such as Linda Perkins, Elizabeth Ihle, Jeanne Noble, and Ellen Lawson, have completed various studies on African American women's higher education. Other scholars, such as Amy Thompson McCandless, offer thorough and insightful comparisons of the southern white and southern black women's education in the twentieth century. Outside the works by this small group of historians, the experiences of college educated African American women have been marginal. Particularly missing from current studies is any examination of African American women in the midwest. (5) Although African American women's historiography has recently focused on Ohio, Indiana, and Illinois, these works avoid any elaborate discussions of African American women's history in midwestern states west of the Mississippi River su ch as Minnesota, Nebraska, and Iowa. (6) To be sure, this study is not only specific to Iowa, but to African American women who attended the University of Iowa. I contend that racism did not paralyze these women's struggle for equality. They transformed their experiences with racism into a call for social activism, racial uplift, and service to their communities. (7) As Kevin Gaines, Stephanie Shaw and other scholars point out, although African Americans agreed on the ideal of uplift they did not always agree on what types of behavior were appropriate. …

Background: Experimental evidence supports a protective role of Vitamin D level in breast carcinogenesis, but epidemiologic evidence is inconsistent. African Americans have high prevalence of Vitamin D deficiency and the African American women with breast cancer have the highest mortality rate. The aim of this study is to investigate the association of Vitamin D levels with breast cancer risk and disease progression in African American and Hispanic women. Methods: This is a cases-control study of 660 African American and Hispanic women with and without breast cancer in South Los Angeles. Blood samples were collected prior cancer treatment and the serum 25-hydroxyvitamin D (25(OH) D was measured by Quest Diagnostics. Information regarding BMI and clinical factors were obtained by medical record abstraction. Logistic Regression with multivariate analysis was used for determining the association of Vitamin D deficiency (<20ng/ml) with breast cancer. Kaplan-Meier survival analysis and Cox Regression with multivariate analysis were used to assess disease-free survival and the relative risk of disease progression. Results: Our data shows that 69.2% of African American women and 37.8% of Hispanic women suffer from Vitamin D deficiency in our cohort. African American women had significant lower level of Vitamin D3 compared with Hispanic women in all age groups. The lower Vitamin D3 level was observed among age groups of 31 to 50 in African Americans. The deficiency in Vitamin D levels was significantly associated with breast cancer in both African Americans (OR=2.5, p=0.007) and Hispanics (OR=1.9, p=0.009). Interestingly, we found that a significant association of Vitamin D deficiency with trip negative breast cancer (TNBC) in African Americans (OR=3.2, p=0.04), but not in Hispanics. The lowest Vitamin D3 level was observed in African American women with TNBC. There was no significant association of Vitamin D deficiency with tumor size, lymph node involvement and tumor stage. The deficiency of Vitamin D3 level was not associated with disease progression in this cohort of women. Conclusion: Our data suggests that a significant association of Vitamin D deficiency with breast cancer in both African Americans and Hispanics, especially more associated with type of TNBC in African American women in our cohort. Citation Format: Yanyuan Wu, Marianna Sarkissyan, Sheilah Clayton, Jay Vadgama. Association of Vitamin D deficiency with breast cancer in African-American and Hispanic women in south Los Angeles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5279. doi:10.1158/1538-7445.AM2017-5279

Ovarian cancer accounts for 5% of cancer deaths and is the fifth leading cause of cancer death in women in the United States. While incidence is higher in European American (EA) than African American (AA) women, five-year survival is worse for AA women (36%) than EA women (44%). Access to appropriate surgery and treatment is a major contributor but does not completely explain this disparity. The Cancer Genome Atlas (TCGA) identified four gene expression-based subtypes of the most common and lethal histotype, high grade serous carcinoma (HGSC): mesenchymal, proliferative, differentiated, and immunoreactive. We sought to characterize similarities and differences in gene expression-based subtypes arising in AA and EA women to determine whether there are underlying biologic features that may influence survival. We performed two distinct analyses, first using TCGA data and second using cases from the population-based African American Cancer Epidemiology Study (AACES). For both we summarized differential expression patterns for each subtype with moderated t statistic vectors for >10,000 genes using Significance Analysis of Microarrays. We calculated Pearson's correlations of these vectors to determine concordance of expression patterns between subtypes across EA and AA women. In TCGA, we observed correlations of subtype-specific expression patterns between the 24 AA and 475 EA tumors of 0.52-0.60 for each of the four subtypes. Thus, while analogous subtypes can be identified in AA and EA women, the magnitude of these correlations suggests that there are potential differences in gene expression patterns between AA and EA tumors that are assigned to the same subtype. We generated additional data from 58 AACES HGSC cases using the Affymetrix Human Transcriptome Array 2.0. Instead of assigning these tumors to previously-defined subtypes, we clustered samples to identify four subtypes de novo. We observed concordance with two of the TCGA subtypes; correlations for the mesenchymal-like and proliferative-like subtypes were 0.56-0.65. The mesenchymal-like subtype was more common in these AA women than in the TCGA EA women (33% versus 25%), and the proliferative-like subtype was marginally less common (14% versus 19%). Concordance for the differentiated-like subtype was considerably lower, at 0.21, and this subtype was less common in AA than EA women (19% versus 34%). Another subtype comprising 34% of the AA samples was only weakly correlated (-0.21-0.10) with any of the TCGA subtypes, suggesting that it is a novel subtype. The limited data available on HGSC in AA women suggest that at least two subtypes are comparable to those in EA women but differ in prevalence, and that there may be a novel subtype in AA women that does not strongly correspond to those described in EA women. Citation Format: Jennifer A. Doherty, Casey S. Greene, James E. Rudd, Laura J. Tafe, Anthony J. Alberg, Elisa V. Bandera, Jill Barnholtz-Sloan, Melissa Bondy, Michele L. Cote, Ellen Funkhouser, Patricia G. Moorman, Edward S. Peters, Ann G. Schwartz, Paul Terry, Rex Bentley, Andrew Berchuck, Jeffrey R. Marks, Joellen M. Schildkraut. Gene expression subtypes of high grade serous ovarian cancer in African American women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3407.

Background: African American (AA) women are more likely to have breast cancer at a younger age and be diagnosed with triple negative breast cancer (TNBC), which is as yet unexplained. We examined results of multi-gene panel testing in AA women with TNBC tested at a large commercial laboratory to assess the utility of gene panels and findings in this group. Methods: We assessed individuals who had clinical hereditary cancer testing with a multi-gene panel between September 2013 and May 2018. Women were included for analysis if they had a personal history of TNBC and self-identified as having any AA ancestry (n=3,268) or only Caucasian (CA) ancestry (n=8,953). Clinical data was collected from provider-completed test request forms. Comparisons were performed using descriptive statistics, t-tests (continuous variables), and chi-square tests (categorical variables) adjusting for multiple testing when necessary. Results: In this cohort, AA women were significantly more likely than CA women to meet NCCN guidelines (97.5% vs. 96.6%, p=0.010) and significantly less likely to have an additional personal (16.2% vs. 21.8%, p<0.001) or family (79.3% vs. 86.3%, p<0.001) history of cancer. Overall, 11.5% of AA women were found to carry a pathogenic variant (PV) compared to 13.4% of CA women (p=0.004; Table 1). Compared to CA women, AA women with a PV were significantly younger at diagnosis (46.7 vs. 49.5 years of age; p<0.001). The prevalence of PVs in BRCA1, CHEK2 and the Lynch syndrome genes was higher in CA women, whereas the prevalence of BRCA2 PVs was higher in AA women. While the prevalence of PVs in individual genes was not significantly different according to ancestry after adjusting for multiple comparisons, AA women were significantly less likely to have a PV in any breast cancer-related gene compared to CA women (p=0.048). AA women were significantly more likely to have a Variant of Uncertain Significance (VUS; 35.6% vs. 20.9%; p<0.001) and to have >1 VUS (8.6% vs. 2.6%, p<0.001). Regardless of ancestry, patients diagnosed before age 40 were more likely to carry a PV (19.7% AA, 22.2% CA). However, the prevalence of PVs among patients diagnosed after age 60 was still striking (8.9% AA, 10.9% CA) and was similar to the PV prevalence among patients diagnosed between 40-60 (10.1% AA, 12.3% CA). Conclusions: In the era of multi-gene panel testing, this large cohort of patients with TNBC supports the use of panel testing in AA women with TNBC regardless of age or additional personal/family history of cancer. While additional research to the rate and pathogenicity of VUS in AA women is needed, genetic counseling is necessary to explain the possibility and meaning of a VUS in this group. Table 1.Distribution of PVs in BC-related genes according to ancestry AA WomenCA WomenGeneN (%)N (%)Any Breast Cancer-Related Gene347 (10.6)1104 (12.3)BRCA1132 (4.0)496 (5.5)BRCA297 (3.0)236 (2.6)ATM6 (0.2)25 (0.3)BARD119 (0.6)67 (0.7)BRIP120 (0.6)46 (0.5)CDH11 (<0.1)1 (<0.1)CHEK22 (0.1)33 (0.4)NBN2 (0.1)10 (0.1)PALB244 (1.3)138 (1.5)PTEN2 (0.1)4 (<0.1)RAD51C20 (0.6)41 (0.5)STK1101 (<0.1)TP532 (0.1)6 (0.1)Lynch Syndrome Genes10 (0.3)46 (0.5)Other Genes12 (0.4)24 (0.3)Multiple PVs6 (0.2)28 (0.3)Total (Any Gene)375 (11.5)1202 (13.4) Citation Format: Pederson HJ, Heald B, Budd GT, Bernhisel R, Cummings S, Saam JR, Lancaster JM, Grobmyer SR, Eng C. Defining the spectrum of germline variants among African American patients with triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-10-01.

Objective: Obesity disproportionately affects African American (AA) women, and there is some suggestion that its association with ovarian cancer risk may be stronger among AA compared to white women, but no study to date has been adequately powered to compare risk between the two populations. The Ovarian Cancer in Women of African Ancestry (OCWAA) Consortium provided a unique opportunity to evaluate the association between body mass index (BMI) and invasive epithelial ovarian cancer (EOC) risk in AA and white women and to estimate the contribution of obesity to ovarian cancer risk in both racial groups. Methods: The OCWAA Consortium is a collaboration of six of the largest epidemiologic studies of ovarian cancer in the United States that include AA women: four case-control and two case-control studies nested within cohort studies. The six studies are the Chicago Case-Control Study, the North Carolina Ovarian Cancer Study, the Los Angeles Ovarian Cancer Case-Control Studies, the African American Cancer Epidemiology Study, the Black Women’s Health Study, and the Multiethnic Cohort. BMI before diagnosis was available in all the studies and data on BMI and relevant confounders were harmonized for analyses. There were 1,144 AA cases, 2,910 AA controls, 3,174 white cases, and 9,160 white controls included. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using random-effects multi-level logistic regression models separately by race and histotype with control for relevant covariates, which included study, age, education, parity, oral contraceptive use, age at menarche and family history of breast/ovarian cancer. Multinomial regression was used for histotype analyses. Population attributable risk (PAR) estimates were computed by race and histotype. Results: The prevalence of obesity (BMI≥30 kg/m2) was higher in AAs compared to white women for both cases (53.2% vs 21.4%) and controls (45.7% vs. 18.4%). For EOC, there was little evidence of an association with obesity for white women. For AAs, risk was elevated for BMI≥30 kg/m2 (ORBMI 30-34=1.37, 95% CI: 1.12, 1.69; ORBMI≥35 = 1.26, 95% CI: 0.74, 2.15) relative to BMI 18.5-<25 kg/m2. There was an elevated risk for non-high-grade serous EOC for both AA and white women (for AA women, ORBMI 30-34=1.67, 95% CI: 1.14, 2.44 and ORBMI≥35 = 1.76; 95% CI: 0.84, 3.69; for white women, ORBMI ≥35 = 1.39; 95% CI: 1.06, 1.82), but not for high-grade serous EOC. The PAR for BMI≥30 was 7.1% (95% CI: 2.4, 15.6) for AAs and 2.6% (95% CI: -0.3, 5.4) for whites for all EOC. For non-high-grade serous EOC, the PAR was 16.5% (95% CI: 3.4, 28.2) for AAs and 6.4% (95% CI: 2.2, 10.3) for whites. Conclusions: Obesity was a contributor to overall EOC risk among AA women but not among white women. Obesity did not contribute to the risk of high-grade serous EOC for AAs or whites, but it was associated with non-high-grade serous cases among both AA and white women. The association with non-high-grade serous EOC was greater among AAs than whites. Citation Format: Elisa V Bandera, Fabian Camacho, Deanna Chyn, Emily K Cloyd, Traci N Bethea, Alicia Beeghly-Fadiel, Charlotte E Joslin, Evan Myers, Patricia G Moorman, Heather M Ochs-Balcom, Holly R Harris, Lauren C Peres, Veronica Wendy Setiawan, Anna H Wu, Lynn Rosenberg, Joellen M Schildkraut. Racial disparities in body mass index and ovarian cancer risk in the OCWAA Consortium [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 C070.

Introduction: African American (AA) women have a lower incidence of breast cancer (BC), however experience higher rates of more aggressive subtypes, mortality, and worse outcomes compared to Caucasian (C) women. Data also points to disparities among treatment access and response in AA women. Most existing genetic research and clinical trials have been conducted with majority C women, thus our existing knowledge about molecular profiles and effective treatments may not be accurate for AA women. The aim of this study is to uncover the biological and social factors related to treatment that may be causing this disparity in BC outcomes between AA and C women. Materials and Methods: Data from Surveillance, Epidemiology, and End Results (SEER) and The Cancer Genome Atlas Program (TCGA) was analyzed for differences in etiology, incidence, and prevalence of BC between AA and C. Prevalence of molecular aberrations and subtypes of BC were assessed to gain insight into potential causes of this disparity. FDA's Drug Trials Snapshots data was assessed for clinical trial enrollment by race. Results: SEER data from 2000-2018 reveals AA patients have higher incidences of TNBC and HER2 enriched BC compared to C, with luminal A incidence being higher in C patients. Within all subtypes of BC, 5-year survival rates were significantly lower for AA compared to C. TCGA data found 2282 genes that were significantly differentially altered in C vs. AA subgroups. Among the most commonly altered and significantly different genes, CSMD1 and TP53 were more prevalent among AA (19.78% AA vs. 10.79% in C for CSMD1, and 40.09% AA vs. 28.58% C for TP53), and PIK3CA among C (36.28% (C) vs. 22.47% (AA)). Survival analysis revealed AA women with PIK3CA alterations had lower rates of disease-free survival compared to C women. Clinical trials for oncology drugs approved in 2020 enrolled 5% AAs, with AAs also being underrepresented for BC specific drugs. The recent NCT02492711 trial of MARGENZA, for metastatic HER2 positive BC, had 5% AA compared to 80% C, the NCT01631552 trial of TRODELVY, for metastatic triple negative BC (TNBC), had 7% AA vs. 76% C, and the NCT02614794 trial of TUKYSA, for advanced HER2+ BC, had 9% AA vs. 73% C. Conclusion: Most existing treatments are for luminal A BC; with fewer approved drugs for subtypes more common among AA women, including the more aggressive TNBC. Recent data indicates that AA women continue to be underrepresented in clinical trials, despite having higher incidence of both HER2 and TNBC, resulting in a poor understanding of effective treatment for this subgroup. These factors may perpetuate disparities in outcomes for AA women with BC. Additionally, TCGA data uncovered underlying molecular differences in BC between AA and C women, some that are actionable. Disparities are multifactorial and can include both biological and socioeconomic factors. Thus, as we move towards more personalized medicine, it is increasingly important to improve representation of AA women in precision oncology trials. Citation Format: Genevra Magliocco, Roy Khalife, Anthony Magliocco. African American women with breast cancer have unique molecular features and reduced clinical trial enrollment [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-099.

Background: Social connections are a basic need of all humans. Loneliness is a perceived lack of both quantity and quality of social relationships. Prior research demonstrates that loneliness increases the risk of cardiovascular disease (CVD) and poor health outcomes. Although African American (AA) women are at greater risk than non-Hispanic White (NHW) women for CVD, the influence of social disadvantages on loneliness in AA women at risk for CVD have not been examined. Purpose: The purpose of this study was to compare protective and risk factors posited to predict loneliness in AA women and NHW women at risk for CVD. Methods: A cross sectional sample of post-menopausal women (50 AA and 49 NHW) with at least two risk factors for CVD completed standardized measures of loneliness, depressive symptoms, financial stress, subjective social status, social support provisions, and resilience. Results: Compared to NHW, AA women reported greater loneliness (t=-2.09, p=.039), financial stress (t=-2.92, p=.004), and lower subjective social status (t=2.68, p=.009). In addition, AA women described less attachment (t=2.34, p=.028) and reliable alliance social support provisions (t=3.27, p=.002) than NHW women. Predictors of loneliness differed between AA and NHW women in that higher levels of depressive symptoms and financial stress and lower levels of resilience, subjective social status, and the social provision of guidance predicted loneliness in AA women in the overall model (r 2 =.91, p=.000). In NHW women, only depressive symptoms and social integration uniquely predicted loneliness (r 2 =.79, p=.000). Conclusions: AA women experienced higher levels of loneliness than NHW women. Although depressive symptoms were a strong predictor of loneliness in both groups, high levels of financial stress and low levels of social status, resilience, and social guidance were unique contributors of loneliness in AA women. Findings from this study may assist researchers in developing and testing tailored interventions to address the effects of social disadvantages on loneliness in vulnerable populations.