Breast Cancer Health Disparities Research Articles

Abstract B132: Vitamin D and breast cancer health disparities: A rapid scoping review investigating the relationship between vitamin D and breast cancer mortality in African American women stratified by molecular subtype

Abstract Introduction: Black women face disproportionate mortality rates from breast cancer because of being more likely to face aggressive breast cancer prognosis and metastasis. Past research findings showed that low vitamin d serum levels are a risk factor for certain types of breast cancer (TNBC, HR+ etc.). Vitamin D deficiency is particularly prevalent amongst black individuals and black women are more likely to experience metastasis and aggressive breast cancer prognosis. However, there is a lack of research on black women that investigates the relationship between vitamin d serum levels and mortality, stratified by prognosis category.   Specific Aim and Hypothesis:  This rapid scoping review is developed to describe the nature, number, and scope of published research articles measuring the association between vitamin D and mortality in black breast cancer patients based on the molecular subtype. a)     Is there a gap in literature to determine if vitamin D has an impact on mortality in black women with breast cancer? If there is an impact, does it vary based on molecular subtype in black women?   Methods: A rapid scoping review will be conducted. Studies that do not provide the following data on African American women with breast cancer will be excluded: breast cancer molecular subtype, mortality status, and vitamin d serum levels pre and post diagnosis. Articles will be reviewed if they were published after 2013 to maintain scientific relevance and must be in the English language. The databases used to conduct the search will be PubMed, Cochran, CINAHL, JBI, web of science, TRIP, and science direct. Studies will be analyzed together based on the type of study (ex. Case-control vs cohort) and when the vitamin D measurements were taken (ex. Pre-diagnosis vs post-diagnosis).   Public Health Implication Identifying potential factors such as lack of vitamin D that contribute to high cancer morbidity and mortality in black women with breast cancer will allow different mechanisms for reducing this cancer disparity.   Citation Format: Adrienne Vaughn. Vitamin D and breast cancer health disparities: A rapid scoping review investigating the relationship between vitamin D and breast cancer mortality in African American women stratified by molecular subtype [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 B132.

THU486 Identification Of Metabolic And Molecular Mechanisms Driving Estrogen Receptor Positive Breast Cancer Disparities Using A Machine-Learning Pipeline

Abstract Disclosure: A. Santaliz Casiano: None. D. Mehta: None. H. Patel: None. G. Rauscher: None. J. Kim: None. J.M. Frasor: None. K. Hoskins: None. Background: African American (AA) women in the United States have a 40% higher breast cancer mortality rate compared with Non-Hispanic White (NHW) women. The survival disparity is particularly striking among ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ positive breast cancer. Methods: We collected pretreatment plasma from AA and NHW ER+ breast cancer cases and cancer-free controls to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC-MS) to identify metabolites that may be altered in the different racial groups. Statistical methods combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from TCGA. Results: We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed changes in metabolites associated with amino acid metabolism, while fatty acid metabolism was significantly enriched in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant association with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene NELFE with histone methyltransferase activity was associated with poor survival exclusively for AA individuals. Conclusion: We employed a comprehensive and novel approach that integrates multiple machine learning methods and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women, and may ultimately lead to identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer, and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities. Presentation: Thursday, June 15, 2023

A Systematic Review of Interpersonal Interactions Related to Racism in Studies Assessing Breast and Gynecological Cancer Health Outcomes Among Black Women.

To identify how studies measure racism-related variables at the interpersonal level and identify associated breast and gynecological cancer disparities among Black women. A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Searches were conducted in PubMed, CINAHL Plus, and Scopus using terms centered on racism and cancer. Inclusion criteria consisted of the study being conducted in the USA with Black or African American women and the study stating an outcome or focus identified as a breast or gynecological cancer health disparity. Two researchers independently screened titles and abstracts and full texts articles and completed quality assessments of included studies. Data were extracted into a matrix table, and common concepts were identified and synthesized using the matrix method. The quality of included studies was assessed using the Joanna Briggs Institute's critical appraisal tools. Thirteen studies that examined the effect of racism-related variables operating at the interpersonal level on breast, cervical, and ovarian cancer outcomes in Black women were identified for inclusion. Across studies, racism-related variables were measured as discrimination, trust, racism, and clinician-patient interactions. Additionally, across studies, disparities were identified in cancer screening, treatment received, survivorship quality of life, and incidence. This review highlights the need for valid, reliable, and consistent measurement of racism operating at the interpersonal level to first understand its impact on cancer health disparities and to also facilitate the development and evaluation of interventions aimed at mitigating interpersonal-level racism.

Identification of metabolic pathways contributing to ER+ breast cancer disparities using a machine-learning pipeline

African American (AA) women in the United States have a 40% higher breast cancer mortality rate than Non-Hispanic White (NHW) women. The survival disparity is particularly striking among (estrogen receptor positive) ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic pathways typically activated in patients with ER+ breast cancer. We collected pretreatment plasma from AA and NHW ER+ breast cancer cases (AA n = 48, NHW n = 54) and cancer-free controls (AA n = 100, NHW n = 48) to conduct an untargeted metabolomics analysis using gas chromatography mass spectrometry (GC–MS) to identify metabolites that may be altered in the different racial groups. Unpaired t-test combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus in AA patients with breast cancer. The clinical relevance of the identified pathways was further examined in PanCancer Atlas breast cancer data set from The Cancer Genome Atlas Program (TCGA). We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed decreased circulating levels of amino acids compared to healthy controls, while fatty acids were significantly higher in NHW patients. By mapping these metabolites to potential epigenetic regulatory mechanisms, this study identified significant associations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases and Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific gene Negative Elongation Factor Complex E (NELFE) with histone methyltransferase activity, was associated with poor survival exclusively for AA individuals. We employed a comprehensive and novel approach that integrates multiple machine learning and statistical methods, coupled with human functional pathway analyses. The metabolic profile of plasma samples identified may help elucidate underlying molecular drivers of disproportionately aggressive ER+ tumor biology in AA women. It may ultimately lead to the identification of novel therapeutic targets. To our knowledge, this is a novel finding that describes a link between metabolic alterations and epigenetic regulation in AA breast cancer and underscores the need for detailed investigations into the biological underpinnings of breast cancer health disparities.

Abstract LB174: Diabetes-associated breast cancer is molecularly distinct and shows DNA repair deficiency

Abstract Diabetes commonly affects cancer patients. In breast cancer, it decreases patient survival. Diabetes also impacts African American women more so than European American women, potentially contributing to the breast cancer health disparity. In this study, we investigated the influence of diabetes on breast cancer biology in a diverse patient cohort using a three-pronged approach that included analysis of orthotopic human tumor xenografts, patient tumors, and breast cancer cells exposed to diabetes/hyperglycemia-like conditions. We aimed to identify shared phenotypes and molecular signatures by investigating the metabolome, transcriptome, and tumor mutational burden. Diabetes does not enhance cell proliferation but induces mesenchymal and stem cell-like phenotypes linked to increased mobility and odds of metastasis. It also promotes oxyradical formation and both transcriptome and mutational signatures of DNA repair deficiency. Moreover, food- and microbiome-derived metabolites tend to accumulate in breast tumors in presence of diabetes, potentially affecting tumor biology. Breast cancer cells cultured under hyperglycemia-like conditions acquire increased DNA damage and sensitivity to DNA repair inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA damage repair inhibitors that are cancer therapeutics. Key words: Breast cancer, diabetes, metabolome, transcriptome, metastasis, DNA repair, mutational signature, health disparity Citation Format: Gatikrushna Panigrahi, Julián Candia, Tiffany H. Dorsey, Wei Tang, Yuuki Ohara, Jung S. Byun, Tsion Zewdu Minas, Amy Zhang, Anuoluwapo Ajao, Ashley Cellini, Harris G. Yfantis, Dean Mann, Olga Ioffe, Xin W. Wang, Huaitian Liu, Christopher A. Loffredo, Ana Maria Napoles, Stefan Ambs. Diabetes-associated breast cancer is molecularly distinct and shows DNA repair deficiency [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB174.

Abstract 510: Targeting metabolic vulnerabilities to reduce triple negative breast cancer health disparities

Abstract Triple negative breast cancer (TNBC) occurs in 10-15% of all breast cancer (BC) patients, yet it accounts for almost half of all BC deaths. Women of African ancestry (WAA) are twice as likely as women of European Ancestry (WEA) to be diagnosed with advanced TNBC with worse prognosis. Emerging data shows that insulin resistance and high circulating levels of insulin are more prevalent in WAA with invasive BCs than in WEA, and activation of the AKT/mTOR pathway by insulin may occur in aggressive TNBC. Reports show diabetic patients treated with metformin, a biguanide drug used to treat diabetes type 2, have reduced incidence of BC and improved survival. However, anticancer actions of metformin require use of high drug doses with limiting side effects in vivo. To address this challenge, we used a structure-activity strategy to develop biguanide analogues with more potent anticancer action and safety at lower doses in vivo. Using TNBC cell proliferation in vitro to screen analogues, promising candidates were identified that exerted dose-dependent inhibition of cell proliferation at significantly lower doses than that of parental metformin (P<0.01). As antitumor effects of metformin are attributed in part to activation of LKB1-AMPK pathways, we find that biguanide analogues also strongly induce AMPK phosphorylation on Western immunoblots and significantly reduce phosphorylation of downstream mTOR signaling pathway components including p70S6K, S6 ribosomal protein and 4E-BP1. Further, analogues induce TNBC cell apoptosis in vitro at lower doses than metformin. In vivo, analogues were more effective than metformin in stopping human TNBC xenograft progression in nude mouse models (P<0.001). Notably, analogues were also more effective than metformin at blocking lung metastases in syngeneic murine 4T1 TNBC models (P<0.05). Transcriptome analyses comparing mammary tumors and lung metastases revealed that analogue JD006 down-regulated genes related to oxidative phosphorylation in lung metastases treated with JD006 and increased expression of genes related to T-cell activation. Further, gene expression in tumors treated with JD006 showed significant down-regulation of long non-coding RNAs that associate with the up-regulation of malignant transformation and activation of M1 macrophages. Importantly, our data indicate that analogue JD006 modulates the activity/trafficking of myeloid-derived suppressor cells (MDSC) and tumor infiltrating lymphocytes (TIL) that may significantly impact TNBC responses to immune checkpoint inhibitors. Further understating of potential biologic differences between TNBC of WAA and WEA is needed to design more effective therapeutic strategies to reduce TNBC health disparities. New targeted treatments could be beneficial for patients afflicted with this deadly disease. (Funding: CBCRP B27IB3869, 4IB-0058; NCI U54 CA143930; JCCC BC Award, Team Research Grant; UCLA TDG). Citation Format: Diana C. Márquez-Garban, Gang Deng, Lorena P. Burton, Gaoyuan Ma, Vishaka Muhunthan, Begonya Comin-Anduix, Gabriela Llarena, Neda Moatamed, Jennifer Murphy, Nalo Hamilton, Daivd Shackelford, Michael E. Jung, Richard J. Pietras. Targeting metabolic vulnerabilities to reduce triple negative breast cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 510.

Using Pointwise Mutual Information for Breast Cancer Health Disparities Research With SEER-Medicare Claims.

Identification of procedures using International Classification of Diseases or Healthcare Common Procedure Coding System codes is challenging when conducting medical claims research. We demonstrate how Pointwise Mutual Information can be used to find associated codes. We apply the method to an investigation of racial differences in breast cancer outcomes. We used Surveillance Epidemiology and End Results (SEER) data linked to Medicare claims. We identified treatment using two methods. First, we used previously published definitions. Second, we augmented definitions using codes empirically identified by the Pointwise Mutual Information statistic. Similar to previous findings, we found that presentation differences between Black and White women closed much of the estimated survival curve gap. However, we found that survival disparities were completely eliminated with the augmented treatment definitions. We were able to control for a wider range of treatment patterns that might affect survival differences between Black and White women with breast cancer.

Abstract P6-05-49: Modeling a public-private grant initiative to address breast cancer care disparities at the community level

Abstract Background: Breast cancer disparities between Black and White women have persisted in the US, with breast cancer death rates 40% higher in Black women compared to White women (American Cancer Society Cancer Facts & Figures for African American/Black People 2022-2024). Education and interventions at the community level can potentially reduce racial gaps, particularly in curbing late-stage diagnoses that disproportionately affect Black women with breast cancer. Together, the American Cancer Society (ACS) and Pfizer Global Medical Grants (Pfizer) developed a collaborative model to support health systems in engaging communities to reduce breast cancer disparities between Black and White women. This collaboration aimed to identify novel interventions and provide foundational support for these communities to advance their work in bridging the gap in breast cancer disparities. Methods: This collaborative grant program divided project responsibilities, in which Pfizer provided funding and ACS provided project oversight and technical support. An advisory committee provided input on the areas of most need, impact and project direction. Funding applicants were required to partner with local organizations to implement evidence-based initiatives for education and/or quality improvement within the respected community. The grant award selection committee comprised of experts in the field, including breast cancer survivors and individuals from racial/ethnic minority groups. In response to a Request for Proposals, over 100 applications were systematically reviewed based on the National Cancer Institute grant selection process. The committee selected 9 grantees with innovative proposals addressing breast cancer disparities for Black women along the cancer-care continuum. Bi-annual progress reports were used to measure progress, with a final report to mark projects’ impact and reach. The COVID-19 pandemic presented numerous obstacles during the project period and the ability to convene with partners virtually through web-based sessions helped to foster opportunities for collaboration and knowledge sharing among leaders in cancer disparities research. Results: The projects occurred from January 2020 to June 2022, with no-cost extensions given to accommodate COVID-19 pandemic delays. During this period grantees successfully completed project goals in one of three areas: screening, identifying areas of need and education. Approximately 10,000 patients and 200 healthcare professions were impacted among three projects focused on increasing mammography efforts in Black women during the project period. Three projects incorporated surveys and focus groups to identify novel areas for intervention/need and interviewed over 350 patients and over 60 health care professionals. The remaining three grantee projects that focused on education successfully implemented advertisement campaigns and lecture series to target patients and healthcare professionals. The projects selected under this model independently completed their goals within the project period while also laying a foundation to continue work in reducing disparities along the cancer care continuum with their enhanced community partner relations. Additionally, the project period also provided opportunities for external collaborations and discussion among all grantees through 8 ACS-coordinated online sessions and 3 summits. Conclusions: Projects selected by the public-private grant initiative model can enhance community relationships and provide infrastructure to continue work along the cancer care continuum. We believe this collaborative competitive grant program can be used for future efforts to address breast cancer and other health disparities at the community level. Similar collaborative funding projects related to prostate and pan-tumor disparities have been launched and are currently ongoing. Citation Format: Emily C. Marlow, Kristen Wehling, Karla Wysocki, Jacqueline Waldrop, Arlen (Dewayne) Brumlow. Modeling a public-private grant initiative to address breast cancer care disparities at the community level [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-05-49.

Abstract A072: Genetic ancestry is related to potential sources of breast cancer health disparities among Colombian women

Abstract Introduction: Socioeconomic disadvantages can contribute to breast cancer health disparities among populations. However, it has been shown that other factors related to the etiology of breast cancer and the biology of the tumor, might also act as determinants of health disparities, as they can impact the patients’ treatment. To date, the relationship between these factors with genetic ancestry in a highly admixed population from Latin-America, has not yet been explored. Based on this, we aimed to assess contributing factors to breast cancer health disparities according to genetic ancestry in Colombian patients from a national cancer reference center. Methods: We revised clinical-pathological and socioeconomic data from breast cancer patients diagnosed at the National Cancer Institute (NCI) of Colombia and classified variables into the following groups: etiology-related factors (e.g., age of diagnosis), tumor-biology factors (e.g., tumor size), and socioeconomic factors (e.g., health insurance), each of which reflects potential sources of racial/ethnic disparities of breast cancer. We also considered variables related to treatment administration (e.g., neoadjuvant therapy) as an indicator of disease management. We applied a Kruskal–Wallis test to assess differences in genetic ancestry fractions according to each of the variables distribution. Results: A total of 308 Colombian breast cancer patients were included. Etiology-related factors analysis showed higher European ancestry fraction in patients diagnosed at older ages (>50 years: 50% vs. ≤50 years: 46%, p=0.017), and with smaller tumors (<20mm: 52% vs. ≥20mm: 48%, p=0.038). Higher Indigenous American (IA) ancestry was observed in patients with HER2-positive tumors compared to HER2-negative cases (44% vs. 40%. p=0.011). Additionally, patients with higher IA ancestry were more frequently treated with neoadjuvant therapy (NAT) (43% vs. no-NAT: 40%, p=0.050). Moreover, socioeconomic variables showed that patients that benefit from the government public health insurance, known in Colombia as subsidized regime, and those who are covered under their relative’s health insurance, known as beneficiaries, have a higher IA ancestry (43% and 43%, respectively, vs. 37%, p=0.016), compared to patients that do afford their own health insurance (contributory regime in Colombia); conversely, these patients presented a higher European ancestry (55% vs. subsidized: 47% and beneficiaries: 49%, p=0.011). Conclusions: Our results indicate that genetic ancestry is related to several potential sources of breast cancer health disparities that cover from tumor-biology factors like tumor size and HER2 expression to socioeconomic determinants like health insurance affiliation regime. Consequently, it is possible that genetic ancestry may partially reflect some differences in the disease management and in healthcare attention given to breast cancer patients in Colombia. Citation Format: Silvia J. Serrano-Gómez, Laura Rey-Vargas, Lina Bejarano, Juan Carlos Mejía-Henao, Maria Carolina Sanabria-Salas. Genetic ancestry is related to potential sources of breast cancer health disparities among Colombian 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 A072.

Abstract IA041: Basic science mechanisms associated with bone tumor microenvironment and health disparities in breast and prostate cancer

Abstract Prostate cancer (PCa) and breast cancer (BCa) are leading causes of cancer related deaths in American men and women, and morbidity is due to metastasis preferentially to bone. Compared to Caucasian American (CA), African American (AA) men and women have a higher bone density, as well as mortality rate due to bone metastasis. Recent studies have shown that high mobility group two (HMGA2), a non-histone chromatin binding protein, plays a critical role in promoting epithelial-mesenchymal transition (EMT) and metastasis. HMGA2 full-length/wild-type and truncated (without the 3’UTR) isoforms have been shown to be overexpressed in several cancers, however their distinct roles in metastasis have not been reported. Our laboratory focuses on tumor-micronenvironmental interactions, particularly, how PCa cells interact with bone at the metastatic site. We have previously published that PCa cells may degrade hydroxyapatite, the major inorganic component of bone, to release calcium which promotes paracrine cell proliferation and migration, and this signaling increases with increased bone density. We hypothesize that EMT is associated with prostate health disparities and that HMGA2 isoforms may play differential roles at the bone metastatic site. We examined EMT marker expression in breast and prostate patient tissue and cell lines by immunohistochemistry (IHC), RNA In Situ Hybridization (RISH), western blot, and real-time PCR. Next, LNCaP PCa cell line stably overexpressing either full length or truncated HMGA2 was co-cultured with low (100 mg) or high (200 mg) hydroxyapatite, demineralized bone matrix or human ground bone matrix, for 6 days followed by collection of condition media (CM). CM was added to parental LNCaP cells for various time points followed by analysis of paracrine cell proliferation using MTS assay, cell migration across collagen using boyden chamber, and the effect on various pathways using western blot analysis. EMT marker (Snail and Cathepsin L) protein expression was higher in AA normal and cancer tissue compared to CA, while it was intermediate in Bahamian tissue. Wild-type HMGA2 mRNA expression was higher in metastatic patient tissue compared to truncated HMGA2, and higher in AA compared to CA tissue. CM taken from LNCaP cells overexpressing wild-type and truncated HMGA2 co-cultured with hydroxyapatite, demineralized bone matrix or ground bone matrix when added to parental LNCaP cells led to higher paracrine cell proliferation and paracrine cell migration. This was associated with MAPK activation that could be abrogated by MAPK inhibitor, UO126. These results indicate that EMT is higher in AA compared to CA. Additionally, both wild-type and truncated HMGA2 interaction with bone matrix promotes paracrine cell proliferation and migration via ERK signaling. Our study shows that wild-type and truncated isoforms of HMGA2 mediate PCa/bone interactions which may lead to increased bone metastasis, particularly in African American men that have higher bone density. Citation Format: Taaliah Campbell, Ohuod Hawsawi, Bor-Jang Hwang, Liza J. Burton, Quentin Loyd, Veronica Henderson, Simone Howard, Camille Ragine, Robin Roberts, Andrew Gachii, Valerie Odero-Marah. Basic science mechanisms associated with bone tumor microenvironment and health disparities in breast and prostate cancer [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 IA041.

Barriers to Mammography Screening among Black Women at a Community Health Center in South Florida, USA.

In the United States (US), Black/African American women suffer disproportionately from breast cancer health disparities with a 40% higher death rate compared to White women. Mammography screening is considered a critical tool in mitigating disparities, yet Black women experience barriers to screening and are more likely to be diagnosed with advanced-stage breast cancer. The purpose of this study was to assess the relative frequency of mammography screening and to examine perceived and actual barriers to screening among women who receive care in our nurse-led community health center. We conducted a survey examining frequency of mammography screening and beliefs about breast cancer including perceived susceptibility, perceived benefits, and perceived barriers to mammography screening, guided by the Champion Health Belief Model. A total of 30 Black/African American women completed the survey. The mean age of the participants was 54.3 years ± 9.17 (SD); 43.3% had a high school education or less; 50% had incomes below $60,000 per year; 26.7% were uninsured; 10% were on Medicaid; and only 50% were working full-time. We found that only half of the participants reported having annual mammograms 16 (53.3%), 1 (3.3%) every 6 months, 8 (26.6%) every 2-3 years, and 5 (16.7%) never had a mammogram in their lifetime. Frequently cited barriers included: 'getting a mammogram would be inconvenient for me'; 'getting a mammogram could cause breast cancer'; 'the treatment I would get for breast cancer would be worse than the cancer itself'; 'being treated for breast cancer would cause me a lot of problems'; 'other health problems would keep me from having a mammogram'; concern about pain with having a mammogram would keep me from having one; and not being able to afford a mammogram would keep me from having one'. Having no health insurance was also a barrier. This study found suboptimal utilization of annual screening mammograms among low-income Black women at a community health center in Florida and women reported several barriers. Given the high mortality rate of breast cancer among Black/African American women, we have integrated a Patient Navigator in our health system to reduce barriers to breast cancer screening, follow-up care, and to facilitate timely access to treatment, thus ultimately reducing breast cancer health disparities and promoting health equity.

Abstract C020: Identification of metabolic and molecular mechanisms contributing to ER+ cancer disparities using a machine-learning pipeline

Abstract Background: African American (AA) women are less likely to develop breast cancer but when they do, their mortality rates are 40% higher compared to Non-Hispanic White (NHW) women. This disparity is particularly striking among ER+ breast cancer cases. The purpose of this study is to examine whether there are racial differences in metabolic and molecular pathways typically activated in patients with ER+ positive breast cancer. Methods: We collected plasma from AA and NHW cases and controls to conduct an untargeted metabolomics analysis using gas chromatography-mass spectrometry (GC-MS) to identify metabolites that are possibly altered in the different race groups. Statistical methods combined with multiple feature selection and prediction models were employed to identify race-specific altered metabolic signatures. This was followed by the identification of altered metabolic pathways with a focus on AA patients with breast cancer. The clinical significance of the findings was further examined in the PanCancer Atlas breast cancer data set. Results: We identified differential metabolic signatures between NHW and AA patients. In AA patients, we observed disturbed amino acid metabolism, while fatty acid metabolism was significant in NHW patients. By mapping these metabolites to genes, this study identified significant relations with regulators of metabolism such as methionine adenosyltransferase 1A (MAT1A), DNA Methyltransferases, Histone methyltransferases for AA individuals, and Fatty acid Synthase (FASN) and Monoacylglycerol lipase (MGL) for NHW individuals. Specific histone methyltransferase NELFE was overexpressed and associated with poor survival exclusively in AA individuals. Conclusion: We employ a comprehensive and novel approach that integrates multiple machine learning methods, and statistical methods, coupled with human functional pathway analyses. This metabolic profile of serum samples might be used to assess risk progression in AA individuals with ER+ breast cancer. To our knowledge, this is a novel finding that describes metabolic alterations in AA breast cancer and emphasizes a potential biological basis for breast cancer health disparities. Citation Format: Ashlie Santaliz Casiano, Zeynep Madak-Erdogan, Dhruv Meta, Jonna Frasor, Garth Rauscher, Kent Hoskins. Identification of metabolic and molecular mechanisms contributing to ER+ cancer disparities using a machine-learning pipeline [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 C020.

The Digital Divide in Radiology: Computer Use for Health Care-related Tasks and Breast Cancer Screening.

HomeRadiologyVol. 306, No. 1 PreviousNext Original ResearchHealth Policy and PracticeThe Digital Divide in Radiology: Computer Use for Health Care–related Tasks and Breast Cancer ScreeningPeter Abraham , Patricia Balthazar, Nicholas James Reid, Efrén J. Flores, Anand K. NarayanPeter Abraham , Patricia Balthazar, Nicholas James Reid, Efrén J. Flores, Anand K. NarayanAuthor AffiliationsFrom the Department of Radiology, University of California, San Diego, 9300 Campus Point Dr, Mail Code 7893, La Jolla, CA 92037 (P.A.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Ga (P.B.); Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (N.J.R., E.J.F.); and Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, Wis (A.K.N.).Address correspondence to P.A. (email: [email protected]).Peter Abraham Patricia BalthazarNicholas James ReidEfrén J. FloresAnand K. NarayanPublished Online:Aug 30 2022https://doi.org/10.1148/radiol.220796MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In AbstractReliance on digital patient portals and online scheduling may exacerbate existing health disparities in breast cancer screening.Download as PowerPoint

Abstract 6141: Understanding the role of gp78 in breast cancer health disparities

Abstract Background: Breast cancer is a devastating disease where death rates for women of African ancestry (AA) are 40% higher than that of European ancestry (EA), demonstrating racial disparity in mortality. gp78 protein is an independent predictor of poor outcomes in women of AA that is over-expressed in aggressive breast cancers. The purpose of this research was to understand how gp78 is associated with poor survival rates by studying tumor biology and gene expression. We hypothesize a positive correlation between the overexpression of gp78 protein in higher amounts for AA women than that of European ancestry women which may correlate with specific functional pathways. Methods: Medical data was collected from a health disparities cohort in Eastern North Carolina. The patient’s race, ethnicity/ancestry were self-reported at the initial visit; the study cohort was reported as 50% AA. Immunohistochemistry to measure protein expression, DNA mutation & gene expression used with Gene Set Enrichment Analysis(GSEA) of 147 patients to identify functional pathway differences in tumor biology between high versus low gp78 expression versus gp78 expression based on patient race. Hierarchical clustered heatmaps were used to compare overlapping genes that were differentially expressed. Results: 49 common genes were identified as the overlap between the genes in the differential gene expression list for gp78 and the two different gene set enrichment analyses compared: GSEA based on patients expressing high versus low gp78 protein by IHC versus GSEA based on white vs black patients (race). The hierarchical cluster analysis of the gene expression patterns identified two prominent clusters: association by extracellular factors in the tumor microenvironment and association by mitochondrial regulation and proliferation. Conclusions: This study suggests that gp78 differences based on race may be linked to tumor microenvironment, mitochondrial function, & proliferation linking gp78 as a biomarker that is differentially expressed based on race and more highly correlated with breast cancer aggressiveness to functional properties of mitochondrial metabolism & tumor microenvironment. We will explore this gene signature/biomarker that may predict survival based on race. This discovery provides new areas of research to explore the relationship of extracellular factors in the tumor microenvironment, mitochondria regulation, & proliferation. Clinical & nonclinical interventions addressing racial health disparity in mortality should target breast cancer-specific health determinants (both environmental and biological) among those of AA with efforts to decrease racial disparities in mortality rates. These new observations indicate gp78 may be a biomarker that can predict survival based on race using tumor biology, which can contribute to new strategies for reducing the rate at which women of AA disproportionately suffer from breast cancer mortality. Citation Format: Sediqua Sherese Bufford. Understanding the role of gp78 in breast cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6141.

Overall survival is the lowest among young women with postpartum breast cancer

BackgroundWomen diagnosed with breast cancer prior to age 45 years (<45y) and within the first 5 years postpartum (postpartum breast cancer, PPBC) have the greatest risk for distal metastatic recurrence. MethodsPooling data from the Colorado Young Women Breast Cancer cohort and the Breast Cancer Health Disparities Study (N = 2519 cases), we examined the association of parity, age, and clinical factors with overall survival (OS) of breast cancer over 15 years of follow-up. ResultsWomen with PPBC diagnosed at <45y had the lowest OS (p < 0.0001), while OS of nulliparous cases diagnosed at <45y did not differ from OS of cases diagnosed at 45-65y regardless of parity status. After adjustment for study site, race/ethnicity, clinical stage, year of diagnosis and stratification for oestrogen receptor status, PPBC remained an independent factor associated with poor OS. Among cases diagnosed at <45y, nulliparous cases had 1.6 times better OS (hazard ratio (HR) = 0.61, 95%CI 0.42–0.87) compared to those with PPBC, with a more pronounced survival difference among stage I breast cancers (HR = 0.30, 95%CI 0.11–0.79). Among very young women diagnosed at age ≤35y, nulliparous cases had 2.3 times better OS (HR = 0.44, 95%CI 0.23–0.84) compared to PPBC. ConclusionOur results suggest that postpartum status is the main driver of poor prognosis in young women with breast cancer, with the strongest association in patients diagnosed at age ≤35y and in those with stage I disease.

YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer.

Simple SummaryTriple negative breast cancer (TNBC) is a devastating disease that affects many women, due to the lack of FDA-approved targeted therapy. In the absence of cell surface receptors ER, PR, and Her2 that can be targeted with hormonal and antibody treatments, cytotoxic chemotherapy remains the major course of treatment, with a dismal response and rapid recurrence due to the acquisition of resistance. TNBC is also twice as more prevalent in African American (AA) when compared to Caucasian American (CA) women. This study investigated the role of the YB1 gene in the disparities in TNBC between AA and CA women. We found that YB1 is highly expressed in TNBC tumors of AA origin when compared to CAs. Increased expression levels and activity of YB1 correlates with poor disease outcomes, resistance to chemotherapy, and the activation of the cancer stem cell (CSC) phenotype, with higher levels in AA than in CA TNBC tumors. More importantly, we found that the targeted inhibition of the expression and activity of YB1 significantly inhibited the oncogenic behavior of AA tumors through sensitization to chemotherapy and inhibition of CSCs. Our study is the first to show that YB1 activity may be a major biological contributor to the health disparities in TNBC, and that development of therapies that specifically target YB1 could reduce these disparities.Triple negative breast cancer (TNBC) is the most aggressive amongst all breast cancer (BC) subtypes. While TNBC tumors represent less than 20% of all BC subtypes, they are responsible for the most BC-related deaths. More significantly, when considering TNBC incidence across all racial/ethnic groups, TNBC accounts for less than 20% of all BCs. However, in non-Hispanic black women, the incidence rate of TNBC is more than 40%, which may be a contributing factor to the higher BC-related death rate in this population. These disparities remain strong even after accounting for differences in socioeconomic status, healthcare access, and lifestyle factors. Increased evidence now points to biological mechanisms that are intrinsic to the tumor that contribute to disparate TNBC disease burdens. Here, we show that YB1, a multifunction gene, plays a major role in the TNBC disparities between African American (AA) and Caucasian American (CA) women. We show in three independent TNBC tumors cohorts, that YB1 is significantly highly expressed in AA TNBC tumors when compared to CAs, and that increased levels of YB1 correlate with poor survival of AA patients with TNBC. We used a combination of genetic manipulation of YB1 and chemotherapy treatment, both in vitro and in animal models of TNBC to show that YB1 oncogenic activity is more enhanced in TNBC cell lines of AA origin, by increasing their tumorigenic and aggressive behaviors, trough the activation of cancer stem cell phenotype and resistance to chemotherapeutic treatments.

Abstract A08: Cadmium elicits a differential cytotoxic response in triple-negative breast cancer cells

Abstract Understanding the relationship between heavy metal exposure and triple-negative breast cancer cells may help to elucidate the high breast cancer mortality rate and health disparity in African-American women, as they may be exposed to these heavy metals at higher rates when compared to their Caucasian counterparts. Triple-negative breast vancer (TNBC) accounts for about 15% of all breast cancers and is characterized by cancer cells that lack the expression of estrogen, progesterone, and HER2/Neu receptors. For this reason, TNBC cells do not respond to hormone therapies or HER2/Neu-targeted treatments. The human body utilizes some metals in small amounts as micronutrients; however, metals such as cadmium-2 that are introduced to the body are not needed physiologically. Human exposure to trace metals in higher-than-needed amounts or exposure to nonessential metals can cause damage to the body as they can be toxic or even carcinogenic. Here we expose the TNBC cell lines HCC 1806 and HCC 70 to cadmium-2. While less is known about the long-term carcinogenic potential of cadmium exposure in the broader population and for other organs, evidence suggests its potential association to lung, breast, and endometrial cancer and mortality. Previous lab data revealed that exposure to high concentrations of cadimum-2 ions causes a differential cytotoxic cell death response in TNBC cells and demonstrates different genotoxic targets and implications in their mutagenic potential when HCC 1806 and HCC 70 cell lines were exposed to this ion. Here, the cell lines have been treated with 5 ug/ml of cadmium-2 ion, revealing increased toxicity using the lactate dehydrogenases assay (LDH), decreased viability (MTS assay), and flow cytometry reveals an abrogation of the cell cycle. The LDH assay revealed that the cells exposed to cadmium resulted in a P-value less than 0.0001 and assay data present percent cytotoxicity of 14.13 and 12.58, respectively, for control and treated cells. A similar trend was exhibited in HCC 70, where the LDH assay resulted in a p-value less than 0.0001 and assay data demonstrated a percent cytotoxicity of 11.57 and 6.92, respectively, for control and treated cells. The MTS assay alongside trypan blue exclusion assay demonstrated a trend of decreasing viability among the treated cells. The flow cytometric analysis revealed an increase in the S-phase in the cadmium-treated cells compared to the controls. These results are potentially early indicators of a molecular effect of Cd ions on breast cancer cells that could elucidate the role that cadmium may play in promoting the aggressive behavior of TNBC or could potentially lead to future treatment regimens. Citation Format: Sherette Godfrey, Checo Rorie. Cadmium elicits a differential cytotoxic response in triple-negative breast cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A08.

Abstract C070: Social determinants of health disparities in triple-negative breast cancer in Louisiana

Abstract Introduction: Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. TNBC patients have generally high risk of recurrence and metastasis, and treatment options remain limited, as there are no effective targeted therapies available. In USA, TNBC is diagnosed disproportionately more frequently in African American (AA) women than in European American (EA) women. We set out to investigate the role of social determinants in racial disparities in TNBC. Methods: TNBC patients diagnosed in Louisiana from 2010-2012 were identified from the Louisiana Tumor Registry. Patients were geocoded to census tract of residence at time of diagnosis. Census tract population and socioeconomic measures were obtained from the US Census American Community Survey. We used multilevel statistical models to analyze the role of neighborhood concentrated disadvantage index (CDI), a robust measure of physical and social environment, in racial disparities in TNBC incidence, stage at diagnosis, and stage-specific survival for the study population. CDI scores were calculated according to the PhenX Toolkit protocol. Results: We identified 1,216 women with TNBC for the study. Controlling for age, we found that AA women had a 2.21-fold risk of TNBC incidence compared to EA in Louisiana. Results from multivariate analyses indicated that the incidence of TNBC was independent of neighborhood CDI, as was the racial disparity. However, CDI did explain existing racial disparities in both stage at diagnosis and stage-specific survival. The odds of diagnosis at later stages were 42% higher for black women. A single standard deviation increase in CDI increased the hazard of breast cancer-related death by 19%. Overall, our results suggest that the increased incidence of TNBC in black women is independent of CDI, while neighborhood environment has a greater impact than race on the promotion and progression of the disease. The socioeconomic disadvantage experienced by black women coupled with increased biologic risk for TNBC contribute to the large racial disparity in breast cancer mortality in Louisiana. Further research is needed to determine the mechanisms through which social determinants affect the promotion and progression of this disease and guide efforts to improve overall survival. Citation Format: Fokhrul Hossain, Denise Danos, Aubrey Gilliland, Claudia Leonardi, Tekeda Ferguson, Neal Simonsen, Qingzhao Yu, Om Prakesh, Richard Scribner, Lucio Miele. Social determinants of health disparities in triple-negative breast cancer in Louisiana [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C070.

Abstract D010: Developing an inflammatory breast cancer campaign: Results from focus groups led by Komen scholars

Abstract Introduction: Breast cancer (BC) remains the second leading cause of cancer deaths amongst women worldwide. In the United States, African American and Latino women are disproportionately burdened by the incidence and mortality of BC compared with Caucasian women. Inflammatory breast cancer (IBC) is a rare and aggressive form of BC. African American women are more likely to be diagnosed with IBC and at earlier age compared to whites. IBC frequently lacks a breast lump and hence is difficult to detect. IBC is often diagnosed late at stage III or IV and has worse prognosis than non-IBC BC. Critically, awareness of IBC continues to lag education on other breast cancers. Lifesaving information and resources to reduce cancer risks are not widespread amongst minority populations. Community engagement is a valuable asset that enhances the traditional biomedical scientist’s knowledge in understanding the connection between biological and social factors affecting a particular disease, with the goal of addressing, and ultimately diminishing, BC health disparities. Methods: The purpose of the focus groups were to determine the best methods and messages for community outreach to raise awareness about IBC. To follow up on our initial listening session at the 4th Annual Women’s Health Awareness Day at NCCU, several focus groups were engaged, each with 10-12 participants from various gender, racial, and economic demographics, recruited from the Raleigh and Durham communities. Participants were provided informed consent forms and demographic surveys to complete. With guidance and training from the Komen mentoring team, trainees crafted a marketing plan and focus group session guide. Trainees served as session moderators and note-takers and developed summary reports which highlighted themes from the sessions which included the following topics: knowledge of IBC, best methods for sharing health information, types of messages to raise awareness and promote action, and perceived barriers to breast cancer screening. Results: Information gathered from the focus group sessions provides a unique perspective to strategize and develop marketing campaigns to bring awareness to the community and minority populations in the community. Many participants were unfamiliar with IBC, how it is diagnosed, and treatment options. To better raise awareness about IBC, participants recommended the use of various social media platforms, promoting more one-on-one education, patient self-advocacy sessions, and changing the perception of the presence of lumps as an indicator of BC. Conclusion: Cancer incidence and mortality overall are declining in all groups in the United States; however, minority groups continue to suffer with increased risk of developing or dying from BC. Furthermore, there is a significant need to raise awareness and understanding of IBC in diverse communities. Partnerships between the community and researchers will facilitate the development of relevant and accessible information about IBC. Citation Format: Portia L Andrews, Alanna Burwell, Maria S Dixon, Hamzah Kharabsheh, Dana M Gant, Tia A Tate, Hassan Shehata, Jodie M Fleming, Kearston L Ingraham, Seronda A Robinson, Nadine J Barrett, Kevin P Williams. Developing an inflammatory breast cancer campaign: Results from focus groups led by Komen scholars [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 D010.

Abstract B072: Cadmium elicits a differential cytotoxic response in triple-negative breast cancer cells

Abstract Understanding the relationship between heavy metal exposure and triple-negative breast cancer cells may help to elucidate the high breast cancer mortality rate and health disparity in African-American women, as they may be exposed to these heavy metals at higher rates and/or their cells may react more negatively to the heavy metals when compared to their Caucasian counterparts. Triple-negative breast cancer (TNBC) accounts for about 15% of all breast cancers and is characterized by cancer cells that lack the expression of estrogen, progesterone, and HER2/Neu receptors. For this reason, TNBC cells do not respond to hormone therapies or HER2/Neu targeted treatments. The human body utilizes some metals in small amounts as micronutrients; however, many metals such as cadmium-2, chromium-6, arsenic, lead, and mercury that are introduced to the body are not needed physiologically. Human exposure to trace metals in higher-than-needed amounts or exposure to nonessential metals can cause damage to the body as they can be toxic or even carcinogenic. Here we expose the TNBC cell line HCC 1806 to Cadmium-2. While less is known about the long-term carcinogenic potential of cadmium exposure in the broader population and for other organs, evidence suggests its potential association to lung, breast, and endometrial cancer and mortality. Previous lab data revealed that exposure to high concentrations of Cadimum-2 ions causes a differential cytotoxic cell death response in TNBC cells and demonstrates different genotoxic targets and implications in their mutagenic potential when HCC 1806 cell lines were exposed to this ion. Here, the cell line HCC 1806 has been treated with 5 ug/ml of Cadmium-2 ion, revealing increased toxicity using the lactate dehydrogenases assay (LDH), decreased viability (MTS assay), and flow cytometry reveals an abrogation of the cell cycle. The LDH assay revealed that the cells exposed to cadmium resulted in a P-value less than 0.0001 and assay data present percent cytotoxicity of 5.1 and 10.7, respectively, for control and treated cells. The MTS assay alongside trypan blue exclusion assay demonstrated a trend of decreasing viability among the treated cells. The flow cytometric analysis revealed an increase in the S-Phase in the cadmium treated cells compared to the controls. These results are potentially early indicators of a molecular effect of Cd ions on breast cancer cells that could elucidate the role that cadmium may play in promoting the aggressive behavior of TNBC or could potentially lead to future treatment regiments. Citation Format: Sherette Godfrey, Checo Rorie. Cadmium elicits a differential cytotoxic response in triple-negative breast cancer cells [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B072.