Survival For African-American Women Research Articles

Racial and Ethnic Disparities in the Time to Ovarian Cancer Surgery in Patients at an Integrated Health Care Delivery System.

Disparities in ovarian cancer survival for African American women are multifactorial. We evaluated racial and ethnic differences in time to ovarian cancer surgery in members of an integrated health care system. In this retrospective cohort study, we identified women diagnosed with invasive epithelial-type ovarian cancer between January 1, 2008, through December 31, 2014, at an integrated health care system in the United States. We extracted data on cancer-related variables and sociodemographic variables from the health care system's cancer registry and electronic health records. We included patients who received ovarian cancer surgery without neoadjuvant chemotherapy. We defined time to surgery as the number of days between diagnostic imaging study and surgery. We used Cox proportional hazards regression to evaluate crude and adjusted association of race and ethnicity with time to surgery. Of 872 patients included, 55.1% were non-Hispanic White (hereafter, White), 24.9% were Hispanic, 14.6% were Asian/Pacific Islander (PI)/Native American, and 5.5% were African American. Median age at diagnosis was 59.0 years. African American patients were diagnosed at an older age and were more likely to come from deprived neighborhoods than other racial and ethnic groups. Median time to surgery was longer for African American patients compared with White, Hispanic, and Asian/PI/Native American patients (median days: 27.5 vs 21.0, 24.5, and 26.0, respectively; P<.0001). In adjusted models, the likelihood of having received surgery at any given time post diagnostic imaging was 31% lower for African American patients compared with White patients (HR, 0.69; 95% CI, 0.51-0.93). This likelihood was also lower for Hispanic and Asian/PI/Native American patients, but not statistically significant. Our findings showed that patients with ovarian cancer from racial and ethnic minorities had a lower likelihood of having received surgery at any given time post diagnostic imaging compared with White patients, demonstrating that racial and ethnic differences exist in time to ovarian cancer surgery in patients with relatively equal access to care.

Abstract B089: Understanding the relationship between neighborhood disorder, racial segregation, and ovarian cancer survival in African American women

Abstract Black women have a 10% lower 5-year survival of epithelial ovarian cancer (EOC) than White women, despite having a 25% lower incidence of OC than White women. Evidence suggests that these health disparities can be partially explained by neighborhood social and environmental factors such as disorder. We used Google Street View (GSV) imagery to estimate a measure of neighborhood disorder (ND) at the block group level within the largest multi-state cohort study of Black women diagnosed with EOC (AACES) between 2010 and 2015. 592 AACES participants were enrolled and geocoded residing in 544 unique block groups. We used the online Computer Assisted Neighborhood Visual Assessment System (CANVAS), to conduct virtual audits at 5 street address locations in each block group. These audits included questions related to the presence of different types of land use, the quality of the built structures, and the presence of other markers of ND. Factor analysis identified 5 distinct neighborhood factors: developmental intensity, development age, neighborhood disorder, land use, and green/blue space. An ND score was calculated for each block group audited based on the ND factor, which included the condition of residential units and yards, and assigned to the residents of that block group. Initial analyses indicated that this score did not impact EOC survival. We conducted Weibull AFT survival analyses with frailty to assess the impact of racial segregation on the relationship between ND and EOC survival. An Isolation Index was calculated to quantify the segregation of non-Hispanic Blacks compared to other racial groups. Increased racial isolation was associated with decreased survival (HR: 1.234, 95%CI: 1.03-1.60), after adjustment. Additionally, to understand the impact of the social aspects of disadvantage compared to the built aspects of our disorder score, we examined ADI as a predictor of EOC survival. Increasing ADI was associated with marginally decreased survival (HR: 1.002, 95%CI: 1.00-1.01), after adjustment. The lack of association between our disorder score and EOC survival and the presence of an association between the measures of racial isolation and ADI and EOC survival could indicate that it is the social aspects of an environment, not the built factors, that are driving EOC survival. Future research should explore the impacts of racial segregation and individual-level perceived racism on EOC survival. Citation Format: Christopher Pierson, Steve J. Mooney, Andrew B. Lawson, Joellen M. Schildkraut, Edward S. Peters. Understanding the relationship between neighborhood disorder, racial segregation, and ovarian cancer survival in African American women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B089.

Abstract C094: The impact of neighborhood disorder on ovarian cancer survival in African American women

Abstract Ovarian cancer (OC) is the fifth-leading cause of cancer deaths in women in the US. While the incidence of ovarian cancer in Black women is 25% lower than in White women, the 5-year survival for Black women is 10% lower than in White women. Recent evidence suggests that health disparities can be partly explained by neighborhood social and environmental factors such as disadvantage or disorder. To test whether objective neighborhood (dis)order is associated with OC survival we developed a novel approach using Google Street View (GSV) to estimate a measure of neighborhood disorder (ND) at the block group level within the largest multi-site cohort study of Black women diagnosed with OC (AACES) between 2010 and 2015. 592 AACES participants were enrolled and geocoded residing in 544 unique block groups largely concentrated in the southern US at their time of diagnosis. We randomly sampled 5 unique street address locations in each block group and adapted an online application, the Computer Assisted Neighborhood Visual Assessment System (CANVAS), that uses Google Street View to conduct virtual audits of the neighborhood environment at these points. We trained and standardized auditors to conduct two independent audits per location, for a total of 5,440 audits. Audit questions assessed the presence of different types of land use, quality of the built structures, and presence of other markers of ND. To understand the underlying patterns in the audit data, we conducted an exploratory factor analysis that identified 5 distinct neighborhood factors: developmental intensity, development age, neighborhood order, land use, and green/blue space. A score for each block group was calculated for each factor and assigned to residents of that block group. The neighborhood order factor included the condition of residential units and yards, as well as the presence of abandoned residential units and empty alcohol containers. The blue/green-space element included the presence of open spaces, recreational facilities, agricultural and waterfront land uses, and trees lining the streets. Survival analysis using Cox Proportional Hazards models was completed, focused on the neighborhood disorder and green/blue-space scores. After adjusting for age, income, education, comorbidity, and state of residence, higher neighborhood order scores were non-significantly associated with longer survival among participants (Hazard Ratio (HR): 0.95, 95% CI: 0.84-1.08). Similarly, higher green/blue space scores were also non-significantly associated with longer survival (HR: 0.92, 95%CI: 0.74-1.15), after adjustment. We observed that OC survival was longer among residents of block groups with higher neighborhood order scores and higher blue/green space scores, though we cannot rule out chance in these associations. Future research should explore mechanisms by which neighborhood features might affect ovarian cancer survival. Citation Format: Christopher Pierson, Steve J. Mooney, Andrew B. Lawson, Joellen M. Schildkraut, Edward S. Peters. The impact of neighborhood disorder on ovarian cancer survival in African American women [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C094.

Tumor immune cell clustering and its association with survival in African American women with ovarian cancer.

New technologies, such as multiplex immunofluorescence microscopy (mIF), are being developed and used for the assessment and visualization of the tumor immune microenvironment (TIME). These assays produce not only an estimate of the abundance of immune cells in the TIME, but also their spatial locations. However, there are currently few approaches to analyze the spatial context of the TIME. Therefore, we have developed a framework for the spatial analysis of the TIME using Ripley’s K, coupled with a permutation-based framework to estimate and measure the departure from complete spatial randomness (CSR) as a measure of the interactions between immune cells. This approach was then applied to epithelial ovarian cancer (EOC) using mIF collected on intra-tumoral regions of interest (ROIs) and tissue microarrays (TMAs) from 160 high-grade serous ovarian carcinoma patients in the African American Cancer Epidemiology Study (AACES) (94 subjects on TMAs resulting in 263 tissue cores; 93 subjects with 260 ROIs; 27 subjects with both TMA and ROI data). Cox proportional hazard models were constructed to determine the association of abundance and spatial clustering of tumor-infiltrating lymphocytes (CD3+), cytotoxic T-cells (CD8+CD3+), and regulatory T-cells (CD3+FoxP3+) with overall survival. Analysis was done on TMA and ROIs, treating the TMA data as validation of the findings from the ROIs. We found that EOC patients with high abundance and low spatial clustering of tumor-infiltrating lymphocytes and T-cell subsets in their tumors had the best overall survival. Additionally, patients with EOC tumors displaying high co-occurrence of cytotoxic T-cells and regulatory T-cells had the best overall survival. Grouping women with ovarian cancer based on both cell abundance and spatial contexture showed better discrimination for survival than grouping ovarian cancer cases only by cell abundance. These findings underscore the prognostic importance of evaluating not only immune cell abundance but also the spatial contexture of the immune cells in the TIME. In conclusion, the application of this spatial analysis framework to the study of the TIME could lead to the identification of immune content and spatial architecture that could aid in the determination of patients that are likely to respond to immunotherapies.

Abstract P3-14-14: A mediation analysis of racial disparity in breast cancer survival

Abstract Introduction: Non-Hispanic Black (African American, AA) women have the worst breast cancer outcomes of any racial/ethnic group. In comparison to non-Hispanic white (white) women, disparities in breast cancer survival for AA women have persisted over the past several decades, although there has been some recent improvement both at the national level and for AA women in Florida. However, we recently reported that AA women in Florida still have twice the rate of breast cancer death compared to their white counterparts. Therefore, more targeted approaches are needed to eliminate survival disparities for AA women diagnosed with breast cancer. The purpose of this study was to conduct a multiple mediation analysis to identify the most important factors causing the disparity in breast cancer survival for AA women. Identifying the most important mediators will provide opportunities for targeted policies, programs, and interventions to ultimately eliminate the prognostic effect of race/ethnicity for Florida women diagnosed with breast cancer. Methods: The study population is comprised of women in Florida diagnosed with breast cancer between 2004 and 2015 who were reported to the Florida Cancer Data System. The following putative mediators were analyzed in this study: residence in high poverty neighborhoods, having Medicaid or no insurance, advanced disease stage at diagnosis, high tumor grade, negative hormone receptor status, and receipt of surgery, based on our causal diagram. The outcome of interest was 5-year breast cancer-specific death. Sociodemographic and clinical characteristics were compared between African American and white women. The Cox model was used to obtain hazard ratios (HR) with 95% confidence intervals (CI) for the direct effect of AA race/ethnicity and indirect effects via mediators. Age was treated as a confounder in the model and mediators were treated as independent. The relative effect for African American ethnicity and each mediator, which is the percentage of the total effect of AA race/ethnicity explained (directly and indirectly) on breast cancer survival, are also provided. Results: African American women were more likely to be younger at diagnosis, living in high poverty neighborhoods, to be insured via Medicaid or uninsured, to have more advanced disease (stage, grade) with hormone receptor negative tumors, and less likely to receive surgery as treatment. From our mediation model, after accounting for all potential mediators, the direct effect associated with African American ethnicity was a 17% (HR = 1.17: 95% CI, 1.11-1.23) increased rate of breast cancer death, which represented 3.9% of the total racial/ethnic effect. The indirect and relative effects of mediators are provided in Table 1. Conclusions: This analysis identified receipt of surgery, advanced disease stage, hormone receptor negative disease, insurance status, and high tumor grade as the most important mediators of the racial/ethnic disparity in breast cancer survival for African American women in Florida. These results have ramifications for increasing access to screening services, providing options for health insurance, and ensuring prompt receipt of curative surgery to eliminate the prognostic effect of race/ethnicity for African American women diagnosed with breast cancer in the Florida. Study limitations are that these results are hypothesis generating based on the current status of methodology to examine multiple mediators in survival models. Table 1.Direct and Indirect Effects for the Association of African American Race/Ethnicity with 5-year Breast Cancer-Specific SurvivalDirect &amp; indirect effectsCox Proportional Hazard ModelHR95%. CIrel effAA race/ethnicity (Direct Effect)1.171.11, 1.233.9%Surgery3.182.93, 3.4728.3%Advanced stage3.092.84, 3.3627.5%Hormone receptor negative1.581.51, 1.6511.1%Medicaid-Uninsured1.481.40, 1.579.6%High grade1.471.42, 1.539.4%High poverty1.341.23, 1.477.2%Hormone treatment1.111.09, 1.142.5%Immunotherapy1.081.02, 1.151.9%Radiation1.041.03, 1.051.0%Chemotherapy0.910.89, 0.92Total Effect60.1050.8, 71.1100.0%Abbreviations: AA, African American; HR, hazard ratio; CI, confidence interval. Citation Format: Robert B. Hines, Xiang Zhu, Eunkyung Lee, Carolyn Rapp, Albert Volk, Asal M. Johnson. A mediation analysis of racial disparity in breast cancer survival [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-14-14.

Cancer-specific and overall survival in African American women with endometrial cancer: a SEER-Medicare study

<h3>Objectives:</h3> To compare the overall survival (OS) and cancer specific survival (CSS) by race for women with stage I-III endometrial cancer (EC) by histologic subtype. <h3>Methods:</h3> This is a retrospective cohort study of women with stage I-III endometrioid, serous, clear cell, and carcinosarcoma who underwent hysterectomy as primary surgical staging as identified within the SEER-Medicare database. Endometrial cancer cases diagnosed between 2000 and 2015 with Medicare enrollment data from 1999-2016 were included. Demographics, cancer data, and survival outcomes were collected. Demographic and treatment factors by race were compared using descriptive analyses. OS and CSS outcomes were stratified by race, stage and histology, then analyzed using log rank tests and multivariate cox modeling (adjusting for age, geographic region, Charlson comorbidity index, post-operative treatment sequencing, FIGO stage, and grade). <h3>Results:</h3> 24,142 total patients were included in this dataset. 85.5% were White, and 8.5% were BlackBlack. 19,351 stage I, 1,484 stage II, and 3,307 stage III cases were identified. Black women were diagnosed at a younger age bracket (40-69yo) than White patients for endometrioid stage I (40% vs 35%), II (37% vs 31%), and III (31% vs 28%); serous stage I (45% vs 31%) and III (42% vs 28%), and carcinosarcoma stage I (39% vs 27%), p<0.05 all. Charlson comorbidity indexes were significantly higher for BlackBlack patients with endometrioid stages I (p<0.001), II (p=0.001), and III (p=0.02) and serous stage I (p<0.0001) and III (p=0.02). Receipt of adjuvant therapy did not differ by race for any stage or histology except for stage III endometrioid where Black women were less likely to receive adjuvant treatment (61.2% vs 70.1% White p=0.03). For stage I, BlackBlack patients had worse CSS and OS for all histologies except clear cell in unadjusted and adjusted analyses (Table I). For stage II, only CSS for endometrioid carcinoma differed by race in unadjusted analyses, whereas OS did not. For stage III, BlackBlack patients with endometrioid carcinoma had worse CSS and OS in unadjusted analyses, but significant survival differences only remained for CSS in the adjusted model. <h3>Conclusions:</h3> Prior studies have reported that BlackBlack women with endometrial cancer have worse survival consistently across stage and histology. However, we did not find this effect when evaluating by CSS and OS. For stage I, BlackBlack women had consistently worse CSS likely related to the disease itself and worse OS in adjusted analyses likely related to poorer overall health outcomes across all histologic subtypes except for clear cell. For stage II and III, racial disparities were seen only for CSS in endometrioid patients in the adjusted analyses, but not OS; and this may have been related to BlackBlack women with stage III cancer receiving less adjuvant therapy. When stratified by stage and histology, BlackBlack women with EC were diagnosed at younger age and with more comorbidities. Overall these findings emphasize the need to intervene in the early stage population, where a disparity exists and the largest population of women is affected.

The Immutable Burden of Racial Disparities in Breast Cancer

The Immutable Burden of Racial Disparities in Breast Cancer

Predicting Survival in African-American Women With Breast Cancer

Predicting Survival in African-American Women With Breast Cancer

Abstract 5318: High-grade serous ovarian cancer DNA methylation and survival in African-American women

Abstract Ovarian cancer is the most lethal gynecologic cancer in the United States, and African-American (AA) women have the poorest outcomes compared to other racial/ethnic groups. Although several biomarkers have been proposed to establish prognosis in European ancestry (EA) patients, including some DNA methylation markers (FGF4, FGF21, MYLK2, MYLK3, MYL7, and ITGAE) (Phelps et al., 2017), it is unknown if these or other markers are applicable to AA patients. Using data from the African-American Cancer Epidemiology Study (AACES), we evaluated 1) if DNA methylation is associated with residual disease and survival, and 2) if previously reported CpG biomarkers for EA women are related to survival in AA women. 121 AA women with high-grade serous ovarian cancer (HGSOC) were randomly selected from 600 women enrolled in AACES. Clinical records and formalin-fixed, paraffin-embedded (FFPE) tumor tissue were retrieved, and a pathologist reviewed histopathologic slides to confirm diagnosis. 92 HGSOC had complete clinical information. DNA methylation was measured using Illlumina HumanMethylationEPIC. Beta-values were preprocessed (RELIC, Tost+BMIQ and ComBat). Low quality probes were filtered. Tumor purity was estimated using InfiniumPurify; &amp;lt;30% was considered low purity. Four cell estimates (RefFreecellmix) were used as a proxy of cell composition. To evaluate DNA methylation alterations, we used the top 100K most variable CpG sites and a semisupervised recursively partitioned mixture model (ssRPMM) approach to delineate the patients into RPMM classes. We also evaluated the six candidate CpGs from Phelps et al. The dataset was divided into training and validation subsets (50% each); if findings were consistent, a pooled statistic is reported. We used logistic regression to evaluate the association between DNA methylation and residual disease; Cox proportional hazard models were used for survival. Models were adjusted for age at diagnosis, low purity, cell types, neoadjuvant therapy, tissue source (adnexa vs. peritoneum), histology (serous vs. mixed), and residual disease. The RPMM classes were not associated with residual disease. For survival, four RPMM classes were delineated, which we collapsed into two classes. A lower risk of mortality was observed for one of the RPMM classes, HR: 0. 03[95% CI: 0.01-0.12]. This “low risk” RPMM class grouped five CpGs in genes PLEC1, AP5B1, DNAH7 and MAPK15. These genes have been associated with cell motility and ovarian cancer ascites. Among the candidate CpGs, we only observed a trend to better survival per every 10% increase in MYLK3 CpG methylation, HR: 0.51 [95%CI: 0.24-1.10]. These preliminary results suggest that some DNA methylation modifications may identify subgroups of AA women with better survival. Previously reported biomarkers in EA may not be as useful in AA women. Future studies with increased sample size may help to disentangle these associations. Citation Format: Lucas A. Salas, Lauren C. Peres, Sarah E. Abbott, Casey S. Greene, Jeffrey R. Marks, Anthony J. Alberg, Elisa V. Bandera, Jill S. Barnholtz-Sloan, Ann G. Schwartz, Michele L. Cote, Patricia G. Moorman, Ellen M. Funkhouser, Edward S. Peters, Melissa L. Bondy, Paul D. Terry, Jennifer A. Doherty, Brock C. Christensen, Joellen M. Schildkraut. High-grade serous ovarian cancer DNA methylation and survival in African-American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5318.

Abstract C32: [Advocate Abstract:] Survivorship and African American women diagnosed with MBC

Abstract The poster will highlight the state of survival for African American women diagnosed with MBC. Citation Format: Yvonne McLean Florence. [Advocate Abstract:] Survivorship and African American women diagnosed with MBC [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr C32.

Abstract A09: Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review

Abstract Certain residential characteristics in urban neighborhoods have shown to have negative impacts on health, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer risk, incidence, stage at diagnosis/late stage diagnosis, survival, and mortality in African Americans. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies that included populations of African American women, setting in “urban” areas, and a measure of a neighborhood or residential factor were reviewed. Three parameters related to neighborhood/residential factors were extracted, including neighborhood socioeconomic status (SES), residential segregation, and residential pollution. Eighteen studies were identified for systematic review. 10 studies showed significantly higher odds of late-stage diagnosis, higher mortality, and lower survival in African American women living in lower socioeconomic neighborhoods. One study showed slightly higher odds of upward neighborhood change and probability of distant metastasis at diagnosis of African American woman compared to White women (OR=1.24). Similarly, 5 studies showed significantly high associations between residential segregation and late-stage diagnosis, as well as high associations of residential segregation and higher mortality in African American women. Two studies assessed residential pollution on breast cancer risk. The first study showed a weak rate of breast cancer risk in African American women between differentiating levels of trihalomethane in public water (RR=1.2). The second assessed the association of magnetic field exposure and breast cancer risk and found that the odds of getting breast cancer were not significant in African American women (OR=1.02). This review provides a qualitative synthesis of major neighborhood and residential factors on breast outcomes in African American women. By enacting health policies and utilizing tools such as health informatics, steps can be taken to drive the breast cancer disparity down in this population. Citation Format: Brandi Patrice Smith, Zeynep Madak-Erdogan. Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A09.

Recreational physical activity and survival in African-American women with ovarian cancer.

While recreational physical activity (RPA) has been associated with reduced mortality in breast, colorectal, and prostate cancers, evidence for epithelial ovarian cancer (EOC) is limited. Most EOC studies have been in predominantly white populations, although inactivity is more prevalent and survival is poorer among African-American (AA) women. We examined RPA before and after EOC diagnosis and associations with survival among AA women. We analyzed data from 264 EOC survivors enrolled in a population-based, case-control study who completed surveys that included questions about pre- and post-diagnosis RPA. Data were collected on RPA frequency, intensity, and duration before diagnosis and approximately 1year after the baseline interview. We calculated metabolic equivalent of task (MET)-hours/week for pre- and post-diagnosis RPA, and evaluated associations with risk of mortality using Cox proportional hazards models. RPA before diagnosis was not associated with mortality. Hazard ratios (HRs) for post-diagnosis RPA were < 1.0 but not statistically significant after adjustment for covariates; HRs were 0.94 (95% CI 0.58, 1.54) for > 0-9 MET-hours/week and 0.53 (95% CI 0.21, 1.35) for > 9 MET-hours/week. Our results suggest that RPA may be inversely associated with mortality among AA women with ovarian cancer, although it is possible that the present study was underpowered to detect an association. There is a clear need for more studies of RPA after diagnosis in EOC survivors with attention to potential differences by race.

Abstract 4131: ERRβ: Validating a novel target for triple negative breast cancer

Abstract Triple negative breast cancer (TNBC) - defined as estrogen receptor- (ER), progesterone receptor- (PR), and human epidermal growth factor receptor 2- (HER2) negative - is a highly aggressive form of breast cancer prevalent in African-American (AA) women. Because ER- and HER2-targeted therapies are ineffective in TNBC, current treatment strategies rely on cytotoxic chemotherapy. There is a tremendous need for new approaches that can identify effective therapies with less toxicity for this devastating form of breast cancer. Nuclear receptors are highly druggable targets. Classical examples include ligand-regulated receptors like ER, but orphan nuclear receptors are also emerging as targets for cancer therapy. We recently published that increased mRNA expression of estrogen-related receptor beta (ERRβ, gene symbol ESRRB) correlates with better recurrence- and distant metastasis-free survival in women with TNBC, and that a small molecule agonist ligand for ERRβ (DY131, DY) has growth inhibitory and anti-mitotic activity in TNBC cell lines of multiple molecular subtypes. The goal of our current work is to validate ERRβ as a novel therapeutic target for TNBC in two distinct ways. First, we sought to determine whether ERRβ is correlated with survival outcome specifically in African-American (AA) women. Analysis of The Cancer Genome Atlas (TCGA) Breast Cancer RNAseq data shows that low ERRβ mRNA expression is specifically associated with poor overall survival in AA women with TNBC. This association is not observed in AA women with ER- or HER2-positive disease. We further find that while ERRβ mRNA expression is decreased in tumor vs. normal breast tissue regardless of race, this decrease is more pronounced in AA women. Ongoing studies in an independent cohort of AA and white women will determine whether this is due, in part, to copy number changes at the ERRβ locus (chromosome 14q24.3). Second, we sought to determine whether ERRβ expression could predict response to current treatment strategies commonly used in breast cancer, particularly TNBC. Using multiple combined datasets, we find that high ERRβ expression is associated with improved recurrence-free survival (RFS) in women with TNBC who received adjuvant or neoadjuvant therapy with anthracycline (e.g. doxorubicin, Adriamycin). No association between ERRβ and RFS is observed in patients treated with taxanes. Ongoing studies in TNBC cell lines seek to determine if activating ERRβ with its agonist ligand DY can enhance doxorubicin-mediated growth inhibition and cell death. Citation Format: Aileen I. Fernandez, Garrett Graham, Balázs Győrffy, Luciane Cavalli, Rebecca B. Riggins. ERRβ: Validating a novel target for triple negative breast cancer [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 4131. doi:10.1158/1538-7445.AM2017-4131

Abstract B03: Racial Variation in Annexin A2 (AnxA2) Gene Expression and Poor Outcome in Triple-Negative Breast Cancer

Abstract Background: Triple-negative breast cancer (TNBC) is identified by the absence of three major receptors (estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2)) that drive most breast cancers. The incidence of TNBC is associated with health disparity due to its disproportionate occurrence in African American (AA) women and its association with worst overall survival in AA women. Previously, our lab in breast cancer has investigated the prevalence, functionality, and mechanistic properties of one of the members of the human annexin family, Annexin A2 (AnxA2), a 36 kDa calcium-dependent phospholipid binding protein. Our previous studies and others have shown that AnxA2 is overexpressed in TNBC and has a reciprocal relationship with HER2 at mRNA and protein levels, but its association with racial variation and clinical outcomes is unknown. Methods: AnxA2 mRNA expression was evaluated in breast cancer subtypes from The Cancer Genome Atlas (TCGA) Breast Invasive Carcinoma (BRCA) mRNA database that includes 1,094 patients. Associations between clinical outcomes and AnxA2 gene expression were tested in a genome wide association study of combined publicly available microarray datasets that includes 4,147 patients (mean follow-up of 69 months). Two tissue microarrays (TMA) consisting of 154 breast cancer patient samples of various subtypes and forty archived paraffin-embedded breast tissues (TNBC and normal tissue) were collected from patients based on ethnicity and analyzed by immunohistochemistry and scored by a clinical pathologist in a blind study to provide scores (0,+1,+2,+3) based on AnxA2 staining intensity. Results: AnxA2 gene expression was significantly increased in TNBC in comparison to other breast cancer subtypes. Furthermore, AnxA2 gene expression was significantly elevated in AA (n=158) women in comparison with Caucasian (CA; n=654, P&amp;lt;0.0001) and Hispanic (HA; n=51, P&amp;lt;0.0001) women and was significantly associated with TNBC in AA women. High expression levels of AnxA2 were associated with reduced overall survival (hazard of death = 2.66; 95% confidence interval {CI] = 1.14 - 6.25, P = 0.0192), reduced relapse free survival (hazard of relapse = 1.45; 95% confidence interval {CI] = 1.12 - 1.89, P = 0.0051), and reduced distant metastasis free survival (hazard of metastasis = 1.7; 95% confidence interval {CI] = 1.00 - 2.91, P = 0.048) in TNBC (basal-like intrinsic subtype). AnxA2 gene expression was not associated with poor outcome in other intrinsic breast cancer subtypes, such as Luminal A, Luminal B, and Her-2, indicating the specific association of AnxA2 with the aggressive behavior of TNBC. Analysis of breast tumor subtypes and normal tissues confirmed that AnxA2 is highly expressed in TNBC compared to its low to negligible expression in other subtypes and normal tumors. Conclusion: AnxA2 overexpression is associated with racial variation and is a potential prognostic and diagnostic candidate for TNBC. Impact: AnxA2 has potential prognostic and diagnostic value, implicating a role for AnxA2 in the aggressive biology of TNBC in AA women. Citation Format: Lee D. Gibbs, Pankaj Chaudhary, Jamboor K. Vishwanatha. Racial Variation in Annexin A2 (AnxA2) Gene Expression and Poor Outcome in Triple-Negative 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 B03.

Abstract IA42: Risk factors and ovarian cancer in African American women: Contributors to disparities

Abstract IA42: Risk factors and ovarian cancer in African American women: Contributors to disparities

Breast cancer survival in African-American women by hormone receptor subtypes.

Breast cancer accounts for over 200,000 annual cases among women in the United States, and is the second leading cause of cancer-related deaths. However, few studies have investigated the association between breast cancer subtype and survival among African-American women. We analyzed cancer-related deaths among African-American women using data obtained from the SEER database linked to the 2000 U.S. census data. We examined distribution of baseline socio-demographic and clinical characteristics by breast cancer subtypes and used Cox proportional hazard models to determine associations between breast cancer subtypes and cancer-related mortality, adjusting for age, socio-economic status, stage at diagnosis, and treatment. Among 19,836 female breast cancer cases, 54.4% were diagnosed with the HER2-/HR+ subtype, with the majority of those cases occurring among women ages 55 and older. However, after adjusting for age, stage, and treatment type (surgery, radiation, or no radiation and/or cancer-directed surgery), TNBC (HR 2.34; 95% CI 1.95-2.81) and HER2+/HR- (HR 1.39, 95% CI 1.08-1.79) cases had significantly higher hazards of cancer-related deaths compared with HER2+/HR+ cases. Adjusting for socio-economic status did not significantly alter these associations. African-American women with TNBC were more likely to have a cancer-related death than African-American women with other breast cancer subtypes. This association remained after adjustments for age, stage, treatment, and socio-economic status. Further studies are needed to identify subtype-specific risk and prognostic factors aimed at better informing prevention efforts for all women.

Race is not a factor in overall survival in patients with triple negative breast cancer: a retrospective review.

The purpose of this study was to determine if race is a factor on overall survival when stage at diagnosis is compared. In this study, a total of 93 women with triple negative breast cancer (TNBC) were evaluated for survival outcomes after diagnosis between the year 2000 through 2010. Thirty-five patients (38%) were African American (AA), and 58 patients (62%) were Caucasian. Overall survival rates were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Student’s t-test was used to calculate differences in cancer recurrence and mortality rates by stage and race. Cox proportional hazards ratios were used to determine the association of patient and variables with clinical outcome. Of women diagnosed with stage 1 breast cancer, the overall survival rates for AAs was 100% compared to Caucasians at 94% (95% CI, 0.003 to 19; P = 0.5). For women with stage 2 breast cancer, overall survival for AA women was 85% and for Caucasian women was 86% (HR = 0.8; 95% CI, 0.3 to 2.6; P = 0.73). For advanced stages (stage 3 and 4), survival for AA women were 78% and 40% for Caucasian women (HR = 0.6; 95% CI 0.2 to 1.98; P = 0.43). Rates of recurrence and mortality were not significantly different between AA and Caucasian TNBC patients. After controlling for patient variables, race was not significantly associated with OS (HR = 1.24; 95% CI, 0.32 to 5.08; P = 0.74) when comparing AA to Caucasian patients. Our study suggests that race does not have an effect on overall survival in African American and Caucasian women diagnosed with TNBC in Arkansas.

Abstract A94: Multidisciplinary team approach improves breast cancer survival in minority women

Abstract Background: Approximately 192,370 women were diagnosed with breast cancer in the United States in 2009. This represents approximately 1 in 8 American women facing the challenge of Breast Cancer therapy in their lifetime. Further, more than 40,000 women will die of breast cancer annually. These statistics represent a significant improvement in the U.S. mortality rate for breast cancer. There continues to be a disparity in outcome from breast cancer with a significantly lower survival in African American women and the uninsured. Our multidisciplinary treatment team includes physicians, nurse navigator and clinical trials specialist are all focused on optimizing multimodal treatment, clinical trial participation, improved quality of life and survival. Methods: All patients with invasive breast cancer diagnosed between 2004 and 2008 at our inner city, public safety-net hospital were included in this evaluation. Each patient had a confirmed histological diagnosis of breast adenocarcinoma. Patient demographic data, tumor staging, treatment and outcomes/survival were evaluated. Tumor Registry Data from our institution was compared to data from the National Cancer Database for the above mentioned time period. All patients at our hospital were treated by the same clinicians and staff utilizing a multidisciplinary team approach. Results: There were 120 patients included in this study during the 5 year period. Of these, 4 patients were men. The majority of patients were between age 40 and 60. Our patients were significantly younger at initial diagnosis compared to the national findings. The ethnic distribution of our patient population: 54% African American, 41 % Caucasian, 3% Asian, 1 % American Indian, and 2% other. Evaluation of our payer status demonstrated that approximately 30% of our patients were self-pay and 32% indigent. Only 5% of our patients were insured with managed care organizations and less than 1% had private insurance. Conclusion: Carefully coordinated multidisciplinary team management of patients with breast cancer resulted in improved clinical outcomes regardless of the patient's ethnicity or insurance status. Implementation of best practice protocols (coordinate multidisciplinary team management; nurse navigator and a vibrant clinical trials program) should become standard at all Community hospitals and academic medical centers, particularly medical facilities serving minority and uninsured patients. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A94.

Does equal treatment yield equal outcomes? The impact of race on survival in epithelial ovarian cancer

ObjectiveTo determine if race impacts the survival of patients with epithelial ovarian cancer in a large academic medical center. MethodsDemographic and clinical–pathologic information from patients treated at the University of Chicago from 1992–2007 were analyzed. Continuous variables were analyzed with t tests and categorical variables with chi square tests. Survival curves were evaluated using Kaplan–Meier methods and Cox proportional hazard models were constructed for both overall and disease free survival. Results209 women with epithelial ovarian cancer were included in the study, 163 (78%) white and 46 (22%) African American. The baseline demographic characteristics and clinico-pathologic factors such as disease stage, grading, CA-125 levels, rates of optimal debulking (<1 cm residual tumor), platinum sensitivity and American Society of Anesthesiologists score (ASA) were similar between the groups. The median overall survival for African American women was similar: 37.2 months (95% Confidence Interval (CI): 22.5, 52.9) while it was 34.1 months (95% CI: 27.4, 42.6) for white women. ConclusionsThere is no evidence of a racial disparity in either treatment or survival for ovarian cancer patients treated at a large academic center. Given that large epidemiologic studies suggested a difference in survival between African American and white women, other sources of disparities must be sought.

P53 expression in breast cancer is more likely to predict survival in African-American than Hispanic or white women

10001 Background: Abnormal nuclear accumulation of p53 protein may predict poorer survival &amp; aggressive tumor biology in African-American (AA) women with breast cancer. We hypothesized that compared to Hispanics or whites, survival would be worse for AA women with p53 positive tumors. Methods: Tumors from 195 consecutive AA, 46 Hispanic &amp; 52 white women were evaluated for p53 expression with IHC, using antibody Pab1801 on paraffin embedded tissue, at the SHCC MBCCOP, in Chicago. Staining was scored on the UK Receptor Group 0–8 system with score ≥2 read as positive. Survival was computed by the Kaplan-Meier method &amp; correlated with p53 expression. Univariate analyses were done with two-sided log-rank test &amp; multivariate analysis was done with Cox proportional-hazards model. Results: There were no significant differences between racial groups regarding tumor size, grade, node status, stage, estrogen receptor (ER) status, treatment &amp; p53 expression. Hispanics were significantly younger (p=0.014). For AA, Hispanic &amp; white women respectively, p53 expression was 29.2%, 34.8% &amp; 18.8%. High grade (p=0.0001) &amp; negative ER status (p=0.006) were significantly associated with p53 expression in AA women; similar results were seen in whites (p=0.014 &amp; p=0.031 respectively), however although the trend for grade was similar, only negative ER status was significantly associated with p53 expression in Hispanics. AA women with p53 positive tumors had significantly worse survival compared to AA women with p53 negative tumors (Hazard Ratio=1.945; 95% CI=1.040–3.638; p=0.037). However, comparison of survival between races for women with p53 positive tumors (p=0.793) and also for women with p53 negative tumors (p=0.4027) was not different. Multivariate analysis demonstrated that there was no interaction (p=0.523) between p53 expression &amp; stage as predictors of poor survival in AA women. Conclusions: Analyses between racial groups demonstrated that AA, Hispanic &amp; white women with breast tumors with abnormal p53 expression had similar associations with high tumor grade, negative ER status and survival. However within racial groups, abnormal p53 expression was only able to predict significantly worse survival in AA women. This association appeared to be independent of stage. [Table: see text]