African American Breast Cancer Patients Research Articles

FBXW7 as a Factor of the African American and White Breast Cancer Racial Disparity.

African American womenhave a breast cancer mortality rate 40% higher than Caucasian women. Many contributing factors account for this racial disparity, such as socioeconomic status and the age when women give birth, but even after considering such factors, studies have found that the racial disparity persists, suggesting that genetic factors may play a crucial role in this breast cancer racial inequality. This study utilizes the All of Us database, The Cancer Genome Atlas (TCGA), and an array of bioinformatics tools to integrate differentialmutation and gene expression analyses, aiming to identify genes potentially associated with this racial disparity. Although previous studies have identified genes associated with this breast cancer racial disparity through mutation or gene expression analysis, no studies have considered both simultaneously. Ultimately, this studyconsiders both mutation and gene expression to discovernovel genes linked to this racial disparity. Aftermutation analysis, this study identifiedFBXW7,a gene involved in the destruction of oncogenic proteins, as being associated with this racial inequality. FBXW7 was the only gene that presented differences in both mutation frequency and gene expression between African Americans and Caucasians. The other four candidate genes, such asCOL12A1,whose upregulation plays a critical role in tumor progression, may also be linked to this racial inequality. By combining both mutation and gene expression analysis, this research offers a unique perspective into this issue. Furthermore, the identification ofFBXW7provides insight into this racial disparity, which can contribute to the pursuit of more effective or personalized treatment for both Caucasian and African American breast cancer patients. Finally, the multi-level method presented could possibly apply to other racial disparities, providing a distinctive perspective that cannot be found with other methods.

Abstract B134: Socioeconomic, social, and clinical factors associated with loneliness among African American breast cancer survivors

Abstract Importance: Social connections are an important driver of cancer risk and outcomes and animal studies have shown that social isolation is important to breast cancer initiation and progression. However, limited empirical data are available on perceived loneliness among patient groups who are at increased risk for breast cancer morbidity and mortality. Objectives: The purpose of this study was to characterize the nature and distribution of loneliness in a sample of African American breast cancer patients and identify clinical and social factors having significant independent associations with perceived loneliness among these survivors. Methods: The study included African American breast cancer patients (n=110) who provided self-reported data on loneliness as part of a participating in a prospective observational study and randomized trial that examined stress reactivity using the Trier Social Stress Test. Loneliness was measured using a short form of the Loneliness Scale; scores were dichotomized using the median split to characterize patients as experiencing high versus low levels of loneliness. Multivariate logistic regression analysis was used to identify factors having significant associations with loneliness. Results: Over half (51.82%) of patients reported experiencing high levels of loneliness. Clinical and social factors that had significant independent associations with loneliness included marital status (OR=2.853, CI=1.066, 7.635, p=0.037), financial strain (OR=3.240, CI=1.114, 9.422, p=0.031), and the number of co-morbidities. Compared to patients who did not have any co- morbidities, those who had one, two, or three or more comorbidities had seven (CI=1.066, 40.645; p=0.029), eleven (CI=1.858, 66.716, p=0.008), and eleven (CI=1.757, 65.244; p=0.010) times the odds, respectively, of experiencing loneliness. Conclusions and Relevance: Many African American breast cancer patients in this study reported high levels of loneliness. Greater efforts are needed to identify patients who may benefit from interventions that enhance social connections, especially if they are married, experiencing financial strain, and have co-morbid conditions. Citation Format: Kelsie Campbell, Fatimata Sanogo, Trista Beard, Melanie Jefferson, Bodhour Sahlia, Chanita Hughes Halbert. Socioeconomic, social, and clinical factors associated with loneliness among African American breast cancer survivors [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B134.

Baseline sLAG-3 levels in Caucasian and African-American breast cancer patients.

Worse survival persists for African-Americans (AA) with breast cancer compared to other race/ethnic groups despite recent improvements for all. Unstudied in outcomes disparities to date is soluble LAG-3 (sLAG-3), cleaved from the LAG-3 immune checkpoint receptor which is a proposed target for deactivation in emerging immunotherapies due to its prominent immunosuppressive function in the tumoral microenvironment. A prior study has found that lower sLAG-3 baseline level was associated with poor outcomes. In a cross-sectional study of 95 patients with primary breast cancer (n = 58 Caucasian, n = 37 AA), we measured sLAG-3 (ELISA pg/ml) in pre-treatment blood samples using the non-parametric Mann-Whitney u-Test for independent samples, and, calculated Pearson r correlation coefficients of sLAG-3 with circulating cytokines by race. Mean sLAG-3 level was lower in AA compared to Caucasian patients (1377.6 vs 3690.3, P = .002), and in patients with triple-negative breast cancer (TNBC) compared to those with non-TNBC malignancies (P = .02). When patients with TNBC tumors were excluded from analyses, the difference in sLAG-3 level between AA (n = 21) and Caucasian patients (n = 40) substantially remained (1937.4 vs 4182.4, P = .06). Among Caucasian patients, sLAG-3 was correlated with IL-6, IL-8 and IL-10 (r = .69, P < .001; r = .70, P < .001; and, r = .46, P = .01; respectively). For AA patients, sLAG-3 was correlated only with IL-6 (r = .37, P = .03). We present the first report that African-American breast cancer patients might have comparatively low pre-treatment sLAG-3 levels, independent of TNBC status, along with reduced co-expression with circulating cytokines. The mechanistic and prognostic role of cleaved LAG-3, particularly in disparate outcomes, remains to be elucidated.

Abstract 1014: Disparities of triple negative breast cancer in Mississippi

Abstract Background: Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers nationwide with disparities of incidence and outcomes among races, geographic locations, and other factors. This study is aimed to analyze the differences in the rate of TNBC, patient conditions at time of diagnosis, and death from TNBC among women in Mississippi. Methods: A retrospective study was conducted to serially review breast cancer cases diagnosed in the University of Mississippi Medical Center during May 2016 to May 2023. The entire breast cancer population was then stratified by race. The rate of TNBC, age and BMI at time of diagnosis, the rate of expiration were compared between African American (AA) and Caucasian American (CA) women with breast cancer. Two-tailed Student’s T-test was used to calculate the difference in mean values, and Chi-Square Test was used to compare the difference in rates or percentages. The significant p value was set at p&amp;lt;0.05. Results: In total 291 women with breast cancer, AA patients were 195 (67.01%), CA patients were 88 (30.24%), and other were 8 (2.75%). The mean age of all patients was 58.3 years-old (ranged 24-97). The mean BMI was 31.19. The patients with TNBC were 109 (37.46%) in entire studied population. A total of 32 (1.6%) patients, including 14 TNBC and 18 non-TNBC were expired with an average age of 61.84 and an average survival time of 20 months from diagnosis to expiration. As compared to CA patient population, AA breast cancer patients had onset at younger age (58.08±0.88 vs. 59.18±1.36), had a higher BMI (31.79±0.62 vs. 28.25±1.05, p=0.017), higher percentage of TNBC (41.54% vs. 30.68%, p=0.082 and OR=1.605), and higher rate of expiration (11.28% vs, 9.1%). Also, as compared to CA expired patients with breast cancer, AA expired patients had higher BMI (29.57 vs. 28.61), shorter survival time (17.5 months vs. 19.4 months), and died at younger age (61.84-year old vs. 66.38-year old) with a higher proportion of TNBC subtype (54.6% vs 12.5%, p=0.045, OR=9.6). Conclusions: Breast cancer is greatly disparate racially between AA and CA and geographically between Mississippi and US national average. The disparities are manifested in the proportion of TNBC subtype, age at onset of breast cancer, BMI at time of diagnosis, and death rate. Citation Format: Navdeep Kaur, Javaria A. Khan, Jinghe Mao, Diva Melvin, Muhammad M. Hassan, Xinchun Zho. Disparities of triple negative breast cancer in Mississippi [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1014.

O 25 - Evidence of LET-dependent RBE on acute radiation dermatitis in Caucasian and African-American breast cancer patients undergoing proton beam therapy

O 25 - Evidence of LET-dependent RBE on acute radiation dermatitis in Caucasian and African-American breast cancer patients undergoing proton beam therapy

Navigator utilization among African-American breast cancer patients at a Comprehensive Cancer Center.

Patient navigation has been demonstrated to improve access to standard-of-care oncologic therapy. However, many patients - particularly those of African-American race - often do not have access to navigation upon receiving a diagnosis of cancer. As the most common cancer among African-American women is breast cancer, we sought to assess the rate of patient navigation among African-American breast cancer patients at our institution, which resides in a regional ZIP code comprised of 46% African-American residents. African-American breast cancer patients who had been discussed at our weekly breast cancer multidisciplinary tumor board over a recent three-month period were assessed by a patient navigator representing the Navigator-Assisted Hypofractionation (NAVAH) program to determine their access to navigation in their cancer care. Responses were assessed from a breast cancer support group and culled to determine a baseline proportion of navigation utilization. A total of 18 women of African-American race having been diagnosed with breast cancer were identified and assessed. Of these a total of 4 noted that they had received navigation, yielding a navigation utilization percentage of 22.2% among African-American breast cancer patients at our institution. The rate of navigation utilization among African-American breast cancer patients is poor. Despite our center residing in a region comprised of increased African-Americans, such predominance has not translated into optimizing navigation access for African-American breast cancer patients. This 22% rate of navigation utilization serves as a starting benchmark for initiatives such as the NAVAH program to provide tangible improvement in this patient population.

Navigator utilization rates in breast cancer patients by race in a comprehensive cancer center.

e18501 Background: African-Americans have the highest overall cancer death rate and shortest survival time of any racial or ethnic group in the United States. Elucidation of disparities in cancer care access is important since previous work has indicated that when equal access to Radiation Therapy (RT) in prospective randomized trials is granted, race does not independently affect outcomes. The most common cancer studied in African-American radiation therapy (RT) access disparities research is breast cancer. Furthermore, prospective analyses have demonstrated that African-Americans receive hypofractionation following breast-conserving surgery less frequently than Caucasians. As such, the goal of this study is to eventually evaluate the impact of patient navigation on short-course RT access for African-American breast cancer patients. Methods: Our study is a prospective survey-based evaluation of the impact of patient navigation on access to hypo-fractionated RT and financial toxicity in African-American breast cancer patients. As the first step to investigating the impact of patient navigation on RT access in this population, medical records of women with breast cancer in our center (University Hospitals Cleveland Medical Center, Seidman Cancer Center) were identified from support groups. The baseline navigation rate for this population was determined from the initial data collected during tumor board sessions from June 2022 through October 2022. Results: We identified female patients who were diagnosed with breast cancer and thus were eligible for navigation. From June 1st through October 31st, 30 female patients were identified. Nine (30%) were Caucasian and 21 (70%) were African-American. Of the 21 African-American female patients, only four (19%) were connected with patient navigation services. Of the 9 Caucasian female patients, only four (44.4%) were connected with patient navigation services; this difference between African-American and Caucasian patients did not reach statistical significance. The total baseline navigation rate at our center during this period was 26.67% (8 out of 30 patients). Conclusions: Over a recent five-month period, it was determined that the baseline navigation rate for Caucasian female breast cancer patients is numerically more than 2x that of African-American female patients at our comprehensive cancer center. This information is an important precursor to the first investigation of the impact of patient navigation on reducing RT access disparities facing African-American breast cancer patients. We anticipate that after collating and analyzing survey results for patients pre-RT versus post-RT as well as for those with versus without patient navigation, navigation will serve to overcome barriers in compliance to therapy and increase adherence to optimal care.

Immune Profile of Exosomes in African American Breast Cancer Patients Is Mediated by Kaiso/THBS1/CD47 Signaling

African American (AA) women with breast cancer are more likely to have higher inflammation and a stronger overall immune response, which correlate with poorer outcomes. In this report, we applied the nanostring immune panel to identify differences in inflammatory and immune gene expression by race. We observed a higher expression of multiple cytokines in AA patients compared to EA patients, with high expression of CD47, TGFB1, and NFKB1 associated with the transcriptional repressor Kaiso. To investigate the mechanism associated with this expression pattern, we observed that Kaiso depletion results in decreased expression of CD47, and its ligand SIRPA. Furthermore, Kaiso appears to directly bind to the methylated sequences of the THBS1 promotor and repress gene expression. Similarly, Kaiso depletion attenuated tumor formation in athymic nude mice, and these Kaiso-depleted xenograft tissues showed significantly higher phagocytosis and increased infiltration of M1 macrophages. In vitro validation using MCF7 and THP1 macrophages treated with Kaiso-depleted exosomes showed a reduced expression of immune-related markers (CD47 and SIRPA) and macrophage polarization towards the M1 phenotype compared to MCF7 cells treated with exosomes isolated from high-Kaiso cells. Lastly, analysis of TCGA breast cancer patient data demonstrates that this gene signature is most prominent in the basal-like subtype, which is more frequently observed in AA breast cancer patients.

Abstract 3588: Multiplex proteomics profiling with the imaging mass cytometry (IMC) identifies immune cell phenotypes associated with high NOS2/COX2 expression in ER- negative and TNBC patients

Abstract Elevated expression of Inducible Nitric oxide Synthase-2 (NOS2) occurs during acute and chronic inflammation and wound healing processes however, it is also a predictor of bad prognosis in aggressive ER-negative tumors. Overexpression of NOS2 correlates with other prognostic biomarkers making it a unique multifunctional oncoprotein. Cyclooxygenase-2 (COX2) is another enzyme associated with cancer inflammation and is overexpressed in &amp;gt;50% of breast cancers. In our previous studies, we have shown that NOS2/COX2 co-expression is a strong predictor of poor clinical outcome and promotes CD8+ T cell exclusion from tumor epithelia in Triple-negative breast cancers (TNBC). This observation was further explored using multiplexing proteomics technologies. Imaging Mass Cytometry (IMC) has revolutionized tumor microenvironment research by allowing the interrogation of over 35 protein markers simultaneously for the elucidation of the spatial distribution of immune and tumor cells at sub-cellular resolution. Herein, we used multiplex capability IMC to explore the interactions of immune and tumor cell counterparts in ER-negative and TNBC tumors. We employed Formalin-fixed paraffin-embedded (FFPE) tissue from 26 ER-negative and TNBC samples from a clinical cohort of African American breast cancer patients in the Baltimore MD area. We developed a panel of 15 protein metal-labeled antibody markers including antibodies targeting NOS2, COX2, T cells (CD45, CD3, CD4, CD8,) endothelium (CD31), monocytes (CD14), macrophages (CD68), basal markers (α-SMA), cancer stem cells (CD44v6), cancer cells (Pan-CK, B7H4, Cadherin), and serine proteases (granzyme B) secreted by T cells or Natural Killer (NK) cells. Single section slides of 4 µm size were stained with the cocktail of metal-labeled antibodies. Multiple regions of interest (ROIs) representing the tumor and immune cells compartments and tumor-facing stromal cell areas were ablated with the Hyperion Imaging system. The data analysis was performed by the Bodenmiller lab pipeline and VisioPharm software packages. Our preliminary data suggest that patient tumors with high or low NOS2/COX2 expression showed variable levels of CD68 positive macrophage population and T cells. We are currently analyzing the remaining data to understand the cell phenotypes associated with the immunosuppressive and immune-rich clinical samples and performing neighborhood analysis of tumor cells to immune cells and vessels. Citation Format: Milind Pore, Lisa Ridnour, Paul Mallory, Ashley Cardamone, Stephen Lockett, William Bocik, David Wink. Multiplex proteomics profiling with the imaging mass cytometry (IMC) identifies immune cell phenotypes associated with high NOS2/COX2 expression in ER- negative and TNBC patients. [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 3588.

Abstract 1937: Racial differences of epigenome in normal breast tissue reveal biological pathways implicated in racial disparities in breast cancer

Abstract Racial disparity in breast cancer is well recognized. Compared to European American (EA) women, African American (AA) women are more often diagnosed with breast cancer at younger ages, have a more advanced or aggressive disease, and have poorer outcomes. Increasing evidence suggests that biological differences between EA and AA women, particularly differences in epigenetic changes of DNA methylation (DNAm), may contribute to the observed cancer disparity. We hypothesize that racial differences in DNAm in normal breast tissue may reflect distinct genomic susceptibility to breast cancer in different racial groups. Therefore, we investigated epigenome-wide differences of DNAm in normal breast tissue between 178 EA and 272 AA women using the Illumina TruSeq Methyl Capture EPIC library and NGS technology. We identified 17,340 differentially methylated CpG loci (DMLs) between EA and AA women, of which 7,744 were hypermethylated in AA women and 9,596 were hypermethylated in EA women. Pathway analyses of genes annotated to these racial DMLs suggested enrichment of biological processes including cell movement, cell motility, and cell migration, features that are likely linked to the aggressiveness and metastatic potentials of tumor cells. We further examined racial differences in DNAm of breast cancer-related candidate genes and GWAS-identified breast cancer risk loci. Approximately 30% of candidate genes were found to have racial differences in DNAm at more than three CpG sites and these candidate genes were enriched for pathways related to response to stimulus and anatomic structure development. Most interestingly, racial DMLs were found to be enriched for breast cancer risk loci that are associated with risk of estrogen-receptor negative (ER-) breast cancer, treatment response to aromatase inhibitor, and breast cancer-specific morality, phenotypes of which we observed differences between EA and AA breast cancer patients. Our results suggest that racial differences in DNAm in normal breast tissue may induce different biological processes that lead to distinct clinical features of breast tumors observed in EA and AA women and provide an epigenetic mechanism underlying the observed racial disparities. Further research is need to validate the findings of this study. Citation Format: Nan Lin, James Castle, Jinpeng Liu, Chunyan He. Racial differences of epigenome in normal breast tissue reveal biological pathways implicated in racial disparities in breast cancer [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 1937.

Abstract P3-01-15: Real-world effectiveness of palbociclib plus aromatase inhibitors (AI) in African American (AA) patients with metastatic breast cancer (MBC)

Abstract Background: Randomized clinical trials and a growing body of real-world evidence have demonstrated clinical benefit of cyclin dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy for HR+/HER2- (MBC). In the National Comprehensive Cancer Network (NCCN) guidelines, CDK4/6i + AI or Fulvestrant is recognized as a preferred regimen for HR+/HER2- MBC. Disparities in survival and clinical outcomes between AA and white breast cancer patients are well documented, but AA patients were not well represented in CDK4/6i randomized clinical trials. We compared real-world progression free survival (rwPFS) and overall survival (OS) of palbociclib plus AI (PB+AI) vs AI alone in AA patients with HR+/HER2- MBC in US clinical practices. Methods: The Flatiron Health longitudinal database contains electronic health records from &amp;gt;280 cancer clinics representing &amp;gt; 2.4 million actively treated cancer patients in the US. We conducted a retrospective analysis of 270 AA patients from the Flatiron database with HR+/HER2- MBC who started PB+AI or AI as first-line therapy between February 2015 and March 2020, Patients were evaluated from start of PB+AI or AI to September 30, 2020 (Data cutoff date), death, or last visit, whichever came first. OS was defined as months from start of PB+AI or AI to death. Patients were censored at the end of the study if they were living. rwPFS was defined as months from start of PB+AI or AI to death or disease progression, evaluated based on clinical assessment or radiographic scan/tissue biopsy. Cox proportional-hazards models were used to estimate the relative effectiveness of PB+AI vs AI without and with adjustment of baseline demographics and clinical characteristics. Results: Of the 270 eligible patients, 127 (47.0%) were treated with PB+AI and 143 (53.0%) were treated with AI. Median age was 64.0 years in PB+AI patients and 68.0 years in AI patients, respectively. Median follow-up was 24.0 months for PB+AI and 18.2 months for AI treated patients. Compared with AI patients, those treated with PB+AI were more likely to have de novo MBC (48.6% vs 30.8%) and to have ≥2 metastatic sites (41.7% vs 29.4%). Of the PB+AI patients, 82.7% started PB at 125mg/day and 30.7% experienced dose adjustment. Median OS was not reached (NR, 95%CI=(38.2-NR)) in PB+AI patients vs 28.2 months (95%CI=19.2-52.8) in AI patients (HR=0.46, 95%CI=0.31-0.68, p =&amp;lt; 0.001; adjusted HR=0.56, 95%CI=0.36-0.89, p=0.013). Median rwPFS was 18.0 months (95%CI = 12.4 – 26.7) in PB+AI patients and 10.5 months (95%CI=7.0-13.4) in AI patients (HR=0.63, 95%CI=0.44-0.88, p &amp;lt; 0.007; Adjusted HR=0.74, 95%CI=0.47-1.17, p =0.199). Conclusions: This comparative analysis of palbociclib plus AI vs AI alone provides evidence that first-line palbociclib in combination with endocrine is associated with improved effectiveness for AA patients with HR+/HER2- MBC in the real-world setting. Additonal studies with larger cohorts are needed to provide additional evidence of outcomes and safety for AA patients in routine clinical practice. Table. Patient characteristics and effectiveness outcomes Citation Format: Hope Rugo, Xianchen Liu, Benjamin Li, Lynn McRoy, Connie Chen, Rachel M. Layman, Adam M. Brufsky. Real-world effectiveness of palbociclib plus aromatase inhibitors (AI) in African American (AA) patients with metastatic breast cancer (MBC) [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 P3-01-15.

An 8-week exercise study to improve cancer treatment related fatigue and QOL among African American breast cancer patients undergoing radiation treatment: A pilot randomized clinical trial

Cancer treatment related fatigue (CTRF) is one of the most debilitating side effects of adjuvant radiation therapy (RT). Several studies have found that physical activity (PA) may be an effective intervention to decrease fatigue and enhance QOL in cancer survivors. The primary objective of the PEDLAR study is to test the feasibility of an easily administered 8-week structured moderate-intensity PA intervention, delivered concurrently with RT, in reducing CTRF and improving health-related QOL among African-American breast cancer patients. This study is also designed to provide pilot data on the acceptability and adherence of PA interventions in African-American women with breast cancer. It is a prospective, 2-arm, 8-week feasibility trial. Participants are randomized to either a structured, moderate-intensity aerobic training exercise regimen concurrent with radiotherapy or a control group. Participants in intervention group reported high satisfaction with exercise and adherence was >75% for exercise sessions. African-American breast cancer patients in a moderate-intensity 75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk follow-up compared to baseline. The control group participants had marginally higher fatigue at 8-wk follow-up compared to baseline. Participants in the intervention group reported slightly better quality of life at 8-wk follow-up compared to baseline (P = 0.06).

A metabolome-wide case-control study of african american breast cancer patients

BackgroundBreast cancer survivors face long-term sequelae compared to the general population, suggesting altered metabolic profiles after breast cancer. We used metabolomics approaches to investigate the metabolic differences between breast cancer patients and women in the general population, aiming to elaborate metabolic changes among breast cancer patients and identify potential targets for clinical interventions to mitigate long-term sequelae.MethodsSerum samples were retrieved from 125 breast cancer cases recruited from the Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), and 125 healthy controls selected from Chicago Multiethnic Prevention and Surveillance Study (COMPASS). We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) combined with fold change to select metabolic features associated with breast cancer. Pathway analyses were conducted using Mummichog to identify differentially enriched metabolic pathways among cancer patients. As potential confounders we included age, marital status, tobacco smoking, alcohol drinking, type 2 diabetes, and area deprivation index in our model. Random effects of residence for intercept was also included in the model. We further conducted subgroup analysis by treatment timing (chemotherapy/radiotherapy/surgery), lymph node status, and cancer stages.ResultsThe entire study participants were African American. The average ages were 57.1 for cases and 58.0 for controls. We extracted 15,829 features in total, among which 507 features were eventually selected by our criteria. Pathway enrichment analysis of these 507 features identified three differentially enriched metabolic pathways related to prostaglandin, leukotriene, and glycerophospholipid. The three pathways demonstrated inconsistent patterns. Metabolic features in the prostaglandin and leukotriene pathways exhibited increased abundances among cancer patients. In contrast, metabolic intensity in the glycerolphospholipid pathway was deregulated among cancer patients. Subgroup analysis yielded consistent results. However, changes in these pathways were strengthened when only using cases with positive lymph nodes, and attenuated when only using cases with stage I disease.ConclusionBreast cancer in African American women is associated with increase in serum metabolites involved in prostaglandin and leukotriene pathways, but with decrease in serum metabolites in glycerolphospholipid pathway. Positive lymph nodes and advanced cancer stage may strengthen changes in these pathways.

Abstract 474: Integrating imaging and multi-omics data to elucidate racial differences in breast tumor biology to optimize precision oncology approaches and patient outcome

Abstract Background: Racial disparities in breast cancer incidence and clinical outcome have been well characterized. In particular, African American (AA) patients have higher mortality rates than other racial groups. Research into these racial disparities has primarily focused on socioeconomic determinants, with some studies exploring potential molecular determinants and limited biological differences found between AA and Caucasian patient tumors. Tumor intrinsic and extrinsic factors that promote racial differences in breast cancer development and patient outcome are not fully understood and strategies to address this are scarce. As a result, we have developed a platform that combines patient-specific imaging and multi-omics data to elucidate how biological differences integrate to promote racial disparities in tumor behavior and patient outcome. Methods: Imaging and transcriptomic data from over 500 patients were integrated within the SimBioSys TumoScope biophysical modeling software to understand racial differences in tumor biology and coordinated tumor behavior. Results: AA patients have tumors that display higher growth rates, characteristically have higher adipose tissue around the tumor, higher spatial variation in drug secretion, lower spatial variation in blood flow/and increased tumor stiffness. Conclusion: Using a transdisciplinary approach, our results show that metabolic and structural tumor features are associated with the disproportionately poor survival rates observed in AA breast cancer patients. By characterizing racial-specific tumor intrinsic and extrinsic biological factors and their potential interactions, strategies may emerge to personalize clinical management based on racial differences. In this way, precision oncology approaches can be applied to increase life-expectancy for racial minorities with breast cancer. Citation Format: Nicole Liadis, Tyler Earnest, Eduardo Braun, Anu Antony, Lance Munn, Michael Hallock, Daniel Cook, The SimBioSys Team. Integrating imaging and multi-omics data to elucidate racial differences in breast tumor biology to optimize precision oncology approaches and patient outcome [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 474.

Navigator-assisted hypofractionation (NAVAH) to address radiation therapy access disparities facing African-Americans with breast cancer.

BackgroundAfrican-Americans have the highest overall cancer death rate and shortest survival time of any racial or ethnic group in the United States. The most common cancer studied in African-American radiation therapy (RT) access disparities research is breast cancer. The goal of this study is to evaluate the impact of patient navigation on RT access for African-American breast cancer patients.Material and methodsThis study is a prospective survey-based evaluation of the impact of patient navigation on access to hypofractionated RT and financial toxicity in African-American breast cancer patients. The impact of patient navigation on RT access will be collated and analyzed from survey results pre-RT versus post-RT as well as for patients with versus without receipt of patient navigation. The validated COST-Functional Assessment of Chronic Illness Therapy score will be used to compare hypofractionation versus standard fractionated RT financial toxicity for patients with early-stage breast cancer who have received lumpectomy.ConclusionThis is the first study to investigate the impact of patient navigation on reducing RT access disparities facing African-American breast cancer patients. The natural progression of this work will be to expand this model to include additional breast cancer populations most vulnerable to suffering RT access disparities (Native American, Hispanic American, Appalachian) within the United States.

Using a multimodal approach to elucidate racial disparities in breast cancer biology by integrating tumor imaging and -omics data.

e12541 Background: Race-related differences in breast cancer incidence and clinical outcome have been well documented, with many studies focusing on socioeconomic determinants contributing to African American (AA) breast cancer patients having higher mortality rates. Far less is understood about the underlying biological differences in tumors between AA and Caucasian patients. In recent years, there have been more and more individual accounts identifying specific somatic mutations or observed breast tumor behaviors associated with racial disparities in breast cancer. Understanding how these specific observations coincide to give rise to alternative tumor biology in AA women, remains a challenge. Given the multifactorial nature of cancer, we have developed a platform that integrates the combinatorial phenotypic, molecular, and biological hallmarks of cancer. Our technology combines imaging and multi-omics data, providing a systematic approach for understanding race-specific biological differences and how they contribute to patient survival. Methods: Imaging and transcriptomic data from 1108 patients were integrated within the SimBioSys TumoScope biophysical modeling software to understand racial differences in tumor biology, coordinated tumor behavior, and corresponding patient outcome. Results: AA patients have tumors that display higher growth rates, characteristically have higher adipose tissue around the tumor, higher spatial variation in drug/ nutrient delivery, and increased tumor stiffness. We also identified biological features, including tumor/gland density and intertumoral heterogeneity that are prognostic for overall survival even when accounting for race and cancer subtype. Conclusions: Our results outline characteristic biological features that along with race and FDA breast cancer subtype may promote the disproportionately poor survival rates observed in AA breast cancer patients. This is the first study demonstrating a systematic approach being used to elucidate race-specific biological difference that may coordinate to impact patient survival. Our findings emphasize the importance of accounting for racial disparities and patient-specific biology to develop tailored intervention strategies and personalize race-specific clinical management of breast cancer.

Racial/ethnic disparities of cancer treatment disruptions among patients with breast cancer with SARS-CoV-2 infection: An analysis of the ASCO Survey on COVID-19 in Oncology Registry.

6556 Background: The COVID-19 pandemic has led to disruptions in cancer treatment delivery among breast cancer patients in the U.S. However, it is currently unknown whether racial/ethnic disparities exist in cancer treatment disruptions among patients with breast cancer and SARS-CoV-2 infection. Methods: We obtained data from the ASCO Survey on COVID-19 in Oncology Registry (March 2020-July 2021) describing breast cancer patients diagnosed with SARS-CoV-2 during their care treated at 46 practices across the US. Data included patient demographics, SARS-CoV-2 diagnosis and treatment, breast cancer characteristics, and modifications to cancer treatment plans. Breast cancer treatment delay or discontinuation (TDD) was defined as any treatment postponed more than two weeks from the originally scheduled date. We computed adjusted odds ratios (aOR) using multivariable logistic regression, accounting for non-independence of patients within hospitals to evaluate racial/ethnic disparities of TDD. Multivariable models were adjusted for age, sex, number of comorbidities, cancer extent, ECOG performance score, pandemic period based on case peaks ( &lt; 06/2020, 06-12/2020, 01-07/2021), and COVID-19 severity (death/hospitalization/ICU admission/mechanical ventilation). Results: Breast cancer patients (n = 804) with SARS-CoV-2 were mostly aged 50 years and above (75%) and urban residents (83%). The racial/ethnic makeup of the sample included: 13.3% non-Hispanic Black/African American (NH-Black), 11.7% Hispanic/Latinx, 4.9% American Indian/Alaskan Native (NH-AI/AN), 4.6% NH-Asian, and 65% NH-White. At SARS-CoV-2 diagnosis, 736 patients (91%) were scheduled to receive drug-based therapy (78%), radiation therapy (8%), or surgery (6%), of whom 39% experienced TDD. Across treatment modalities, the most commonly reported TDD reason from the clinic perspective was the patient’s COVID-19 disease (̃90%). Overall, NH-Black (62%), Hispanic/Latinx (44%), and NH-Asian (42%) adults with breast cancer and SARS-CoV-2 were more likely to experience TDD versus NH-White adults (34%) (p &lt; 0.001). In multivariable analyses, NH-Black cancer patients were more likely to experience TDD compared to NH-White patients (aOR: 3.12, 95% CI: 1.96-5.47). The data suggest Hispanic/Latinx (aOR: 1.34, 95% CI: 0.78-2.30) breast cancer patients may also experience TDD, although not statistically significant. No association was observed among NH-Asian (aOR: 1.16, 95% CI: 0.50-2.73) or NH-AI/AN (aOR: 0.64, 95% CI: 0.28-1.52) breast cancer patients with TDD. Conclusions: Black or African American breast cancer patients are more likely to experience cancer care disruptions during the pandemic. Future research should evaluate the long-term impacts of care disruptions on breast cancer outcomes among minoritized US communities.

Abstract P3-14-06: A transdisciplinary approach for characterizing racial differences in the biology of breast cancer by integrating imaging and -omics data

Abstract Background: Racial disparities in breast cancer incidence and clinical outcome have become increasingly recognized. In particular, African American (AA) patients have higher mortality rates than other racial groups. Research into these racial disparities has primarily focused on socioeconomic determinants, with some studies exploring molecular determinants. Biologically, few differences in genetics or transcriptomics have been found to be due to race. Understanding racial differences in breast cancer development as they relate to patient outcomes requires a comprehensive approach, integrating tumor intrinsic and extrinsic factors. We have developed a platform that combines patient-specific imaging and -omics data to elucidate how biological differences are integrated to cause racial differences in tumor behavior and disparities in patient outcome. Methods: Imaging and transcriptomic data from over 500 patients were integrated within the SimBioSys TumorScope biophysical modeling software to understand how racial differences in tumor biology are coordinated to determine tumor behavior. Specifically, we used artificial intelligence to automatically segment tumors from patient MRIs, and construct 3D models of patient tumors and the surrounding microenvironment. We then used these segmentations to identify radiological differences between AA and Caucasian patients. Simultaneously, we used patient-specific mathematical models of tumor metabolism constructed from RNA-seq data to determine racial differences in tumor metabolism. Results: We profiled structural differences in 266 tumors (181 Caucasian and 85 AA) and metabolic differences in 552 tumors (422 Caucasian and 130 AA). In our patient cohort, AA tumors were smaller (AA/Caucasian volume = 0.573, p = 0.004), more spherical (AA/Caucasian sphericity = 1.12, p = 0.0046), had lower spatial variation in tumor stiffness (AA/Caucasian Contrast GLRLM Gray Level Non-uniformity = 0.63, p = 0.0004), and had higher vascular perfusion than Caucasian tumors (AA/Caucasian vascular shell density = 1.43, p = 0.0015). In addition, AA tumors had increased levels in several features which may contribute to decreased response to therapy, including a higher spatial heterogeneity in drug delivery and secretion (AA/Caucasian WIS std = 2.2, p = 5.9x10-9, WOS std = 11.5, p &amp;lt; 10-10) and higher levels of adipose surrounding the tumor (AA/Caucasian adipose shell density = 1.13, p = 0.0024). Metabolically, we found that tumors from AA patients have increased sphingolipid metabolism (AA/Caucasian fold change (FC) = 1.4, p = 0.04) and pyruvate metabolism (FC = 1.03, p = 0.03); and decreased starch and sucrose metabolism (FC = 0.89, p = 0.03), fatty acid metabolism (average FC = 0.83, p = 0.04), glycerolipid metabolism (FC = 0.70, p = 0.025), and acylglyceride metabolism (FC = 0.69, p = 0.025). Furthermore, we found that these metabolic features integrate in such a way that tumors from AA patients had an increased specific growth rate (FC = 1.52, p = 0.014), compared to Caucasian patients (even when correcting for PAM50 subtype). Conclusion: Taken together, these results indicate that tumors of AA patients have a more aggressive phenotype (high growth rate) and potentially a lower response to chemotherapeutic drugs (high spatial heterogeneity of drug delivery and secretion and high surrounding adipose). These features likely work together to contribute to the disproportionately poor survival rates repeatedly observed in AA breast cancer patients. By characterizing racial-specific tumor intrinsic and extrinsic biological factor and their potential interactions, TumorScope simulation platform can assist in finding strategies that may improve clinical management, life-expectancy, and overall outcomes of racial minorities with breast cancer. Citation Format: Nicole Liadis, Tyler Earnest, Eduardo Bruan, Anu Antony, Michael Hallock, Daniel Cook. A transdisciplinary approach for characterizing racial differences in the biology of breast cancer by integrating imaging and -omics data [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 P3-14-06.

Abstract PO-096: Caloric restriction may decrease health disparity in AA breast cancer patients due to significant downregulation of the IGF-1R pathway in a window-of-opportunity clinical trial

Abstract Introduction: Health disparities in breast cancer outcomes exist for African American (AA) women who are noted to present with more aggressive cancer with worse survival. Although the underlying reason for this disparity is not apparent, it is likely multifactorial. Interestingly, type 1 insulin-like growth factor receptor (IGF-1R) expression, which plays a critical role in cell growth, survival, and migration, is higher in normal breast tissue in AA women as compared to Caucasian women. Although this has been well established, interventional studies to modulate this pathway have not been performed. We sought to determine if a dietary intervention of caloric restriction could play a role in modulating the IGF-1R pathway to help address the disparities seen in AA breast cancer patients. Methods: On an IRB approved clinical trial, patients were enrolled in a window-of-opportunity clinical trial to assess the effect of caloric restriction, or a 25% reduction of calories from the patients' baseline, on biomarkers in the tumor and blood. Patients recorded their baseline caloric intake for 3-5 days and were then instructed on a target calorie intake for the remainder of the diet. The patients remained on the dietary intervention for 2-12 weeks. Participants had anthropometric evaluation, blood draws to evaluate serum cytokines, tissue collection, and quality of life surveys collected at baseline and completion of diet which was the morning of surgery. Results: We enrolled 19 breast cancer patients between the years 2016 and 2018. The average age of the patients at the time of enrollment was 58 years old with 47% AA and 53% Caucasian. The patients were on the trial for an average of 19 days. Patients lost an average of 4.91 lbs during the trial, with AA patients losing an average of 5.18 lbs and Caucasians losing an average of 4.68 lbs. To determine the importance of IGF-1R in the disparities seen in AA women, we looked at two hundred cytokines from serum samples in patients who underwent caloric restriction. Analysis of the cytokine array data showed that nine cytokines involved in regulating or modulation by the IGF-1R pathway were significantly (p&amp;lt;0.05) downregulated in AA women post-diet. Compared to Caucasian women, AA women showed a significant decrease in IL-12p40 (~51%), VCAM1 (16.8%), IL-2 (28.72%), IL-2Rb (40.81%), CCL28 (36%), ERBB3 (26.6%), PAI-1 (9.4%), Axl (36%) and PDGF-AB (12%). Conclusion: These results demonstrate that caloric restriction significantly downregulated members of the IGF-1R pathway in the AA community. Since this pathway is notably dysregulated in AA patients, an integrated approach, one incorporating dietary changes to alter key pro-survival pathways, should be further investigated to narrow the disparity in breast cancer outcomes in AA patients. Citation Format: Samantha Okere, Anuradha A. Shastri, Kamryn Hines, Pramila Anne, Rita Murphy, Tiziana DeAngelis, Adam Berger, Alliric Willis, Melissa Lazar, Edith Mitchell, Nicole Simone. Caloric restriction may decrease health disparity in AA breast cancer patients due to significant downregulation of the IGF-1R pathway in a window-of-opportunity clinical trial [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-096.

Abstract PR-02: Characterization of pseudogene expression and immune infiltration in breast cancer subtypes for African American and Caucasian patients

Abstract Introduction: Breast Cancer (BC) occurrence, especially triple-negative BC (TNBC), is relatively high among African American women. In addition, Caucasian BC mortality has decreased much faster than African American BC mortality even with advancing medicines over the last few years. Researchers have reported socioeconomic and biological factors that may contribute to African American BC disparity, but concrete genetic biomarkers have not been elucidated. In this study, we conducted a systematic bioinformatics analysis to compare the gene expression pattern and examine the immunological differences in Black and White patients for different breast cancer subtypes. Methods: Using the public portal of The Cancer Genome Atlas (TCGA), Level 3 RNA-Seq expression data and corresponding clinical data for 183 African American and 764 Caucasian BC patients were downloaded. These patients were then categorized by four subtypes (luminal A, luminal B, HER2-enriched, and TNBC) and subsequently analyzed for gene expression and immune infiltration association. The average expression in RPKM (reads per kilobase of transcript per million mapped reads) of transcribed genes for each race and subtype was calculated using a custom R script. For each subtype, the top 30 genes with the highest expression in each race were selected and cross-checked for any overlap. Association between their expression and tumor infiltrates for six immune cell types (B cell, Dendritic cell, Macrophage, Neutrophil, T-cell CD4, T-cell CD8) was assessed using TIMER2.0. Results: For all subtypes, the majority of the top 30 genes overlapped between both races. In particular, 24 out of the top 30 genes (80%) were common between both races for TNBC. Five genes (ADAM6, CD74, LOC96610, B2M, HLA-B) were reported to show strong positive correlation between their expression and immune infiltration. Interestingly, out of the unique gene set for both races in the TNBC subtype, none of them showed strong positive correlation. ADAM6, a transcribed pseudogene, was identified to be positively correlated to immune infiltration in African American BC patients uniquely across all subtypes excluding TNBC in our study. Conclusion: Our computation result provides a candidate list of unique and common genes having high expression for four BC subtypes in African American and Caucasian patients. Our work also suggests that expressed pseudogenes could serve as potential biomarkers for BC patients. We plan to continue to investigate biomarkers in BC subtypes and immune response over post-transcriptional regulatory network in the context of breast cancer etiology. Citation Format: Eric W. Li, Yongsheng Bai. Characterization of pseudogene expression and immune infiltration in breast cancer subtypes for African American and Caucasian patients [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR-02.