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African American (AA) prostate cancer associates with vitamin D3 deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex. Likewise, in AA cells, Assay for Transposase-Accessible Chromatin using sequencing established greater 1α,25(OH)2D3-regulated chromatin accessibility, chromatin immunoprecipitation sequencing revealed significant enhancer-enriched VDR cistrome, and RNA sequencing identified the largest 1α,25(OH)2D3-dependent transcriptome. These VDR functions were significantly corrupted in the isogenic AA RC43T prostate cancer cells, and significantly distinct from EA cell models. We identified reduced expression of the chromatin remodeler, BAZ1A, in three AA prostate cancer cohorts as well as RC43T compared with RC43N. Restored BAZ1A expression significantly increased 1α,25(OH)2D3-regulated VDR-dependent gene expression in RC43T, but not HPr1AR or LNCaP cells. The clinical impact of VDR cistrome-transcriptome relationships were tested in three different clinical prostate cancer cohorts. Strikingly, only in AA patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH)2D3-dependent open chromatin (i) predicted progression from high-grade prostatic intraepithelial neoplasia to prostate cancer; (ii) responded to vitamin D3 supplementation in prostate cancer tumors; (iii) differentially responded to 25(OH)D3 serum levels. Finally, partial correlation analyses established that BAZ1A and components of the VDR complex identified by RIME significantly strengthened the correlation between VDR and target genes in AA prostate cancer only. Therefore, VDR transcriptional control is most potent in AA prostate cells and distorted through a BAZ1A-dependent control of VDR function. Significance: Our study identified that genomic ancestry drives the VDR complex composition, genomic distribution, and transcriptional function, and is disrupted by BAZ1A and illustrates a novel driver for AA prostate cancer.

Since the completion of the Human Genome Project, considerable progress has been made in translating knowledge about the genetic basis of disease risk and treatment response into clinical services and public health interventions that have greater precision. It is anticipated that more precision approaches to early detection, prevention, and treatment will be developed and will enhance equity in healthcare and outcomes among disparity populations. Reduced access to genomic medicine research, clinical services, and public health interventions has the potential to exacerbate disparities in genomic medicine. The purpose of this article is to describe these challenges to equity in genomic medicine and identify opportunities and future directions for addressing these issues. Efforts are needed to enhance access to genomic medicine research, clinical services, and public health interventions, and additional research that examines the clinical utility of precision medicine among disparity populations should be prioritized to ensure equity in genomic medicine.

The capacity and diversity of the oncology leadership workforce has not kept pace with the emerging needs of our increasingly complex cancer centers and the spectrum of challenges our institutions face in reducing the cancer burden in diverse catchment areas. Recognizing the importance of a diverse workforce to reduce cancer inequities, the Association of American Cancer Institutes conducted a survey of its 103 cancer centers to examine diversity in leadership roles from research program leaders to cancer center directors. A total of 82 (80%) centers responded, including 64 National Cancer Institute–designated and 18 emerging centers. Among these 82 respondents, non-Hispanic White individuals comprised 79% of center directors, 82% of deputy directors, 72% of associate directors, and 72% of program leaders. Women are underrepresented in all leadership roles (ranging from 16% for center directors to 45% for associate directors). Although the limited gender, ethnic, and racial diversity of center directors and perhaps deputy directors is less surprising, the demographics of current research program leaders and associate directors exposes a substantial lack of diversity in the traditional cancer center senior leadership pipeline. Sole reliance on the cohort of current center leaders and leadership pipeline is unlikely to produce the diversity in cancer center leadership needed to facilitate the ability of those centers to address the needs of the diverse populations they serve. Informed by these data, this commentary describes some best practices to build a pipeline of emerging leaders who are representative of the diverse populations served by these institutions and who are well positioned to succeed.

ST_13 BAZ1A and lineage plasticity

SF_6 RNA-Seq PCA

SF_8 RNA-Seq GSEA

SF_13 GSEA tumors

Supplementary Table _2 - RIME II

ST_3 ATAC-Seq

SF_3 motifs in ATAC-Seq

African American (AA) prostate cancer associates with vitamin D3 deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex. Likewise, in AA cells, Assay for Transposase-Accessible Chromatin using sequencing established greater 1α,25(OH)2D3-regulated chromatin accessibility, chromatin immunoprecipitation sequencing revealed significant enhancer-enriched VDR cistrome, and RNA sequencing identified the largest 1α,25(OH)2D3-dependent transcriptome. These VDR functions were significantly corrupted in the isogenic AA RC43T prostate cancer cells, and significantly distinct from EA cell models. We identified reduced expression of the chromatin remodeler, BAZ1A, in three AA prostate cancer cohorts as well as RC43T compared with RC43N. Restored BAZ1A expression significantly increased 1α,25(OH)2D3-regulated VDR-dependent gene expression in RC43T, but not HPr1AR or LNCaP cells. The clinical impact of VDR cistrome-transcriptome relationships were tested in three different clinical prostate cancer cohorts. Strikingly, only in AA patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH)2D3-dependent open chromatin (i) predicted progression from high-grade prostatic intraepithelial neoplasia to prostate cancer; (ii) responded to vitamin D3 supplementation in prostate cancer tumors; (iii) differentially responded to 25(OH)D3 serum levels. Finally, partial correlation analyses established that BAZ1A and components of the VDR complex identified by RIME significantly strengthened the correlation between VDR and target genes in AA prostate cancer only. Therefore, VDR transcriptional control is most potent in AA prostate cells and distorted through a BAZ1A-dependent control of VDR function.Significance:Our study identified that genomic ancestry drives the VDR complex composition, genomic distribution, and transcriptional function, and is disrupted by BAZ1A and illustrates a novel driver for AA prostate cancer.

SF_9 overlap miRNA

ST_4 ChIP-Seq

ST_5 ChromHMM

ST_7 ATAC-Seq to RIME

SF_5 ChIP-Seq motif

SF_2 Ancestry cell lines

SF_4 VDR cistrome

ST_6 ChIP-Seq Motif

ST_8 ATAC/ChIP-Seq to splicing

SF_7 RNA-Seq volcanos

Introduction: Primary care providers (PCPs) and oncologists lack time and training to appropriately identify patients at increased risk for hereditary cancer using family health history (FHx) and clinical practice guideline (CPG) criteria. We built a tool, “ItRunsInMyFamily” (ItRuns) that automates FHx collection and risk assessment using CPGs. The purpose of this study was to evaluate ItRuns by measuring the level of concordance in referral patterns for genetic counseling/testing (GC/GT) between the CPGs as applied by the tool and genetic counselors (GCs), in comparison to oncologists and PCPs. The extent to which non-GCs are discordant with CPGs is a gap that health information technology, such as ItRuns, can help close to facilitate the identification of individuals at risk for hereditary cancer. Methods: We curated 18 FHx cases and surveyed GCs and non-GCs (oncologists and PCPs) to assess concordance with ItRuns CPG criteria for referring patients for GC/GT. Percent agreement was used to describe concordance, and logistic regression to compare providers and the tool’s concordance with CPG criteria. Results: GCs had the best overall concordance with the CPGs used in ItRuns at 82.2%, followed by oncologists with 66.0% and PCPs with 60.6%. GCs were significantly more likely to concur with CPGs (OR = 4.04, 95% CI = 3.35–4.89) than non-GCs. All providers had higher concordance with CPGs for FHx cases that met the criteria for genetic counseling/testing than for cases that did not. Discussion/Conclusion: The risk assessment provided by ItRuns was highly concordant with that of GC’s, particularly for at-risk individuals. The use of such technology-based tools improves efficiency and can lead to greater numbers of at-risk individuals accessing genetic counseling, testing, and mutation-based interventions to improve health.

PURPOSE The purpose of this study was to examine racial differences in patient portal activation and research participation among patients with prostate cancer. MATERIALS AND METHODS Participants were African American and White patients with prostate cancer who were treated with radical prostatectomy (n = 218). Patient portal activation was determined using electronic health records, and research participation was measured based on completion of a social determinants survey. RESULTS Thirty-one percent of patients completed the social determinants survey and enrolled in the study and 66% activated a patient portal. The likelihood of enrolling in the study was reduced with greater levels of social deprivation (odds ratio [OR], 0.70; 95% CI, 0.50 to 0.98; P = .04). Social deprivation also had a signification independent association with patient portal activation along with racial background. African American patients (OR, 0.48; 95% CI, 0.23 to 0.91; P = .02) and those with greater social deprivation (OR, 0.58; 95% CI, 0.42 to 0.82; P = .002) had a lower likelihood of activating a patient portal compared with White patients and those with lower social deprivation. CONCLUSION Although the majority of patients with prostate cancer activated their patient portal, rates of patient portal activation were lower among African American patients and those who lived in areas with greater social deprivation. Greater efforts are needed to promote patient portal activation among African American patients with prostate cancer and address access to health information technology among those who live in socially disadvantaged geographic areas.

Achieving health equity among disparity populations has been a national, regional, and local priority for several years. Health promotion and disease prevention behaviors play an important role in achieving health equity; the first generation of behavioral science studies in minority health and health disparities have provided important insights about the nature and distribution of risk exposure behaviors in disparity populations. Interventions have also been developed to enhance health promotion and disease prevention behaviors using behavioral counseling, tailored health communications, and interventions that are developed collaboratively with community stakeholders. Although intervention development and evaluation are components of transdisciplinary translational behavior research, discovery science is a critical first step in translational research. Consistent with this, conceptual models and frameworks of minority health and health disparities have evolved to include multilevel determinants that include basic behavioral mechanisms such as stress responses and stress reactivity that have physiological, psychological, and behavioral components that are relevant to minority health and health disparities. This report describes priorities, opportunities, and barriers to conducting transdisciplinary translational behavioral research during the next generation of minority health and health disparities research.

PURPOSE: More than half of patients with head and neck squamous cell carcinoma (HNSCC) experience a delay initiating guideline-adherent postoperative radiation therapy (PORT), contributing to excess mortality and racial disparities in survival. However, interventions to improve the delivery of timely, equitable PORT among patients with HNSCC are lacking. This study (1) describes the development of NDURE (Navigation for Disparities and Untimely Radiation thErapy), a navigation-based multilevel intervention (MLI) to improve guideline-adherent PORT and (2) evaluates its feasibility, acceptability, and preliminary efficacy. METHODS: NDURE was developed using the six steps of intervention mapping (IM). Subsequently, NDURE was evaluated by enrolling consecutive patients with locally advanced HNSCC undergoing surgery and PORT (n = 15) into a single-arm clinical trial with a mixed-methods approach to process evaluation. RESULTS: NDURE is a navigation-based MLI targeting barriers to timely, guideline-adherent PORT at the patient, healthcare team, and organizational levels. NDURE is delivered via three in-person navigation sessions anchored to case identification and surgical care transitions. Intervention components include the following: (1) patient education, (2) travel support, (3) a standardized process for initiating the discussion of expectations for PORT, (4) PORT care plans, (5) referral tracking and follow-up, and (6) organizational restructuring. NDURE was feasible, as judged by accrual (88% of eligible patients [100% Blacks] enrolled) and dropout (n = 0). One hundred percent of patients reported moderate or strong agreement that NDURE helped solve challenges starting PORT; 86% were highly likely to recommend NDURE. The rate of timely, guideline-adherent PORT was 86% overall and 100% for Black patients. CONCLUSION: NDURE is a navigation-based MLI that is feasible, is acceptable, and has the potential to improve the timely, equitable, guideline-adherent PORT.

OBJECTIVES. Diagnosis-to-treatment interval is an important quality measure that is recognized by the National Accreditation Program for Breast Centers, and the American Society of Breast Surgeons and the National Quality Measures for Breast Care. The aim of this study was to assess factors related to delays in receiving breast cancer treatment. METHODS: This retrospective cohort study (2002 to 2010) used data from the South Carolina Central Cancer Registry (SCCCR) and Office of Revenue and Fiscal Affairs (RFA) to examine racial differences in diagnosis-to-treatment time (in days), with adjuvant hormone receipt, surgery, chemotherapy, and radiotherapy assessed separately. Chi-square tests, logistic regression and generalized linear models were used to compare diagnosis-to-treatment days. RESULTS: Black women on average received adjuvant hormone therapy, surgery, chemotherapy, and radiotherapy 25, 8, 7, and 3 days later than their White counterparts, respectively. Black women with local stage cancer had later time to surgery (OR: 1.6; CI: 1.2-2.2) compared with White women with local stage cancer. Black women living in rural areas had higher odds (OR: 2.0; CI: 1.1-3.7) of receiving late chemotherapy compared with White women living in rural areas. Unmarried Black women also had greater risk (OR: 2.0; CI: 1.0-4.0) of receiving late radiotherapy compared to married White women. CONCLUSIONS: To improve timely receipt of effective BrCA treatments, programs aimed at reducing racial disparities may need to target subgroups of Black breast cancer patients based on their social determinants of health and geographic residence.

The events of 2020 threw into stark relief the long-standing inequities in healthcare and the disproportionate toll they exert on communities of color. We asked physicians and scientists to share their experiences in confronting and tackling health disparities, and their Voices highlight the need for concerted and widespread action.

Prostate cancer is one of the most prevalent cancers worldwide, particularly affecting men living a western lifestyle and of African descent, suggesting risk factors that are genetic, environmental, and socioeconomic in nature. In the USA, African American (AA) men are disproportionately affected, on average suffering from a higher grade of the disease and at a younger age compared to men of European descent (EA). Fusion genes are chimeric products formed by the merging of two separate genes occurring as a result of chromosomal structural changes, for example, inversion or trans/cis-splicing of neighboring genes. They are known drivers of cancer and have been identified in 20% of cancers. Improvements in genomics technologies such as RNA-sequencing coupled with better algorithms for prediction of fusion genes has added to our knowledge of specific gene fusions in cancers. At present AA are underrepresented in genomic studies of prostate cancer. The primary goal of this study was to examine molecular differences in predicted fusion genes in a cohort of AA and EA men in the context of prostate cancer using computational approaches. RNA was purified from prostate tissue specimens obtained at surgery from subjects enrolled in the study. Fusion gene predictions were performed using four different fusion gene detection programs. This identified novel putative gene fusions unique to AA and suggested that the fusion gene burden was higher in AA compared to EA men.

PURPOSE: Delays initiating guideline-adherent postoperative radiation therapy (PORT) in head and neck squamous cell carcinoma (HNSCC) are common, contribute to excess mortality, and are a modifiable target for improving survival. However, the barriers that prevent the delivery of timely, guideline-adherent PORT remain unknown. This study aims to identify the multilevel barriers to timely, guideline-adherent PORT and organize them into a conceptual model. MATERIALS AND METHODS: Semi-structured interviews with key informants were conducted with a purposive sample of patients with HNSCC and oncology providers across diverse practice settings until thematic saturation (n = 45). Thematic analysis was performed to identify the themes that explain barriers to timely PORT and to develop a conceptual model. RESULTS: In all, 27 patients with HNSCC undergoing surgery and PORT were included, of whom 41% were African American, and 37% had surgery and PORT at different facilities. Eighteen clinicians representing a diverse mix of provider types from 7 oncology practices participated in key informant interviews. Five key themes representing barriers to timely PORT were identified across 5 health care delivery levels: (1) inadequate education about timely PORT, (2) postsurgical sequelae that interrupt the tight treatment timeline (both intrapersonal level), (3) insufficient coordination and communication during care transitions (interpersonal and health care team levels), (4) fragmentation of care across health care organizations (organizational level), and (5) travel burden for socioeconomically disadvantaged patients (community level). CONCLUSION: This study provides a novel description of the multilevel barriers that contribute to delayed PORT. Interventions targeting these multilevel barriers could improve the delivery of timely, guideline-adherent PORT and decrease mortality for patients with HNSCC.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death among breast cancer (BC) survivors. BC survivors are at increased risk of CVD due to a higher prevalence of risk factors. Current data is limited on the cardiovascular screening practices and lipid management in this population in primary care settings. METHODS: A retrospective case control study was performed with 105 BC survivors and 210 matched controls (based on age and medical comorbidities of diabetes, hypertension, and hyperlipidemia). BC survivors were established with primary care practices within a large academic institution and had completed primary cancer treatment. Data on screening for CVD and lipid management were collected via a retrospective chart review. RESULTS: The average BC survivor was 63 years old, with 9 years since diagnosis. Compared with matched controls, BC survivors had more cholesterol screening (88% vs. 70%, p

Purpose To examine financial toxicity and strain among men in an equal access healthcare system based on social determinants and clinical characteristics. Methods Observational study among men receiving prostate cancer care (n = 49) at a Veterans Health Administration (VHA) facility. Financial hardship included overall financial strain and financial toxicity due to healthcare costs. Financial strain was measured with one item asking how much money they have leftover at the end of the month. Financial toxicity was measured with the Comprehensive Score for Financial Toxicity (COST) scale. Results Comprehensive Score for Financial Toxicity scores among participants indicated moderate levels of financial toxicity (M = 24.4, SD = 9.9). For financial strain, 36% of participants reported that they did not have enough money left over at the end of the month. There were no racial or clinically related differences in financial toxicity, but race and income level had significant associations with financial strain. Conclusion Financial toxicity and strain should be measured among patients in an equal access healthcare system. Findings suggest that social determinants may be important to assess, to identify patients who may be most likely to experience financial hardship in the context of obtaining cancer care and implement efforts to mitigate the burden for those patients., The purpose of this study was to examine financial toxicity and strain among men in an equal access healthcare system based on social determinants and clinical characteristics. There were no racial or clinically related differences in financial toxicity, but race and income level had significant associations with financial strain. Social determinants should be assessed to identify patients who may be most likely to experience financial hardship in the context of obtaining cancer care in order to implement efforts to mitigate the burden for those patients.

BACKGROUND: The emergence of reactive stroma is a hallmark of PCa progression and a potential source for prognostic and diagnostic markers of PCa. Collagen is a main component of reactive stroma and changes systematically and quantitatively to reflect the course of PCa, yet has remained undefined due to a lack of tools that can define collagen protein structure. Here we use a novel collagen-targeting proteomics approach to investigate zonal regulation of collagen type proteins in PCa prostatectomies. METHODS: Prostatectomies from 9 patients were divided into zones containing 0, 5, 20, 70–80% glandular tissue and 0, 5, 25, 70% by mass of prostate cancer tumor following the McNeal model. Tissue sections from zones were graded by a pathologist for Gleason score, percent tumor present, percent prostatic intraepithelial neoplasia and/or inflammation. High resolution accurate mass (HRAM) collagen targeting proteomics was done on a select subset of tissue sections from patient-matched tumor or nontumor zones. Imaging mass spectrometry was used to investigate collagen type regulation corresponding to pathologist defined regions. RESULTS: Complex collagen proteomes were detected from all zones. COL17A and COL27A increased in zones of inflammation compared to zones with tumor present. COL3A1, COL4A5, and COL8A2 consistently increased in zones with tumor content, independent of tumor size. Collagen hydroxylation of proline (HYP) was altered in tumor zones compared to zones with inflammation and no tumor. COL3A1 and COL5A1 showed significant changes in HYP peptide ratios within tumor compared to zones of inflammation (2.59 ± 0.29 p-value 0.015; 3.75 ± 0.96 p-value 0.036, respectively). By imaging mass spectrometry COL3A1 showed defined localization and regulation to tumor pathology. COL1A1 and COL1A2 showed gradient regulation corresponding to PCa pathology across zones. Pathologist defined tumor regions showed significant increases in COL1A1 HYP modifications compared to COL1A2 HYP modifications. Certain COL1A1 and COL1A2 peptides could discriminate between pathologist defined tumor and inflammatory regions. CONCLUSIONS: Site-specific post-translational regulation of collagen structure by proline hydroxylation may be involved in reactive stroma associated with PCa progression. Translational and post-translational regulation of collagen protein structure has potential for new markers to understand PCa progression and outcomes.

As precision medicine becomes a mainstay in health care, the use of health information technology (IT) platforms will play an important role in the delivery of services across the cancer care continuum. Currently, there is both limited understanding about perceptions of health IT tools and barriers to their use among cancer genetic counselors. We assessed open-ended responses from a survey conducted among 128 board-certified cancer genetic counselors in the United States. We evaluated the utility of ten health IT tools and perceived barriers to adoption. Responses about characteristics of health IT tools that influence current use (i.e., technology-specific challenges) were deductively analyzed using the diffusion of innovations (DOI) characteristics. Responses about cancer genetic counselors' perceived challenges to adopting health IT tools (i.e., discipline-specific challenges) were inductively coded using a thematic approach. DOI innovation characteristics included mixed perceptions about the relative advantage, complexity, compatibility, trialability, and observability of tools based on the type of tool and perceived end-user. One-third of participants indicated that they were considering adopting or switching health IT tools. Common barriers to adoption included no perceived need for change, lack of organizational infrastructure, cost, and lack of decision-making power. Our findings indicate that addressing barriers to use and adoption of health IT may allow for expansion of these tools among cancer genetic counselors. Integrating health IT is critical for enhancing cancer genetic counselors' capacity to address patient needs and realizing the potential of precision medicine.

PURPOSE: Physical activity is important for enhancing quality of life and cancer control among prostate cancer survivors. The purpose of this study was to examine characterize adherence to physical activity guidelines among African American and white prostate cancer survivors based on social and clinical determinants and psychosocial factors. METHODS: Observational study of meeting guidelines for moderate intensity physical activity in a retrospective cohort of African American and white prostate cancer survivors (n=89). RESULTS: Thirty-four percent of survivors met the recommended guidelines for moderate intensity physical activity. There were no racial differences in physical activity between African American and white prostate cancer survivors; however, the likelihood of meeting guidelines was associated significantly with stage of disease, self-rated health, and perceptions of stress. Survivors who had stage pT2c or higher disease had a significantly reduced likelihood of meeting recommended guidelines for physical activity (OR=0.27, 95% CI=0.08, 0.86, p=0.03). The likelihood of meeting guidelines was also reduced among survivors who rated their health as being the same or worse than before they were diagnosed with prostate cancer (OR=0.32, 95% CI=0.11, 0.96, p=0.04). As perceived stress increased, the likelihood of being physically active according to guidelines also decreased (OR=0.48, 95% CI=0.26, 0.89, p=0.02). CONCLUSION: The results of this study underscore the need to develop, implement, and evaluate strategies to enhance physical activity among prostate cancer survivors, regardless of their racial background. Complementary and alternative strategies for physical activity may be one strategy for enhancing activity levels and managing stress among prostate cancer survivors.

Objective: To examine the relationships be­tween resiliency, sociodemographic factors, and allostatic load among male Veterans. Design/Study Participants: Cross-sectional study with minority (African American or Hispanic) and non-minority (White) male Veterans undergoing prostate biopsy. Setting: Veterans Affairs Medical Center located in Charleston, SC. Main Outcome Measures: Self-reported resilience measured using the two item sub-scale from the Connor-Davidson Resiliency Scale and allostatic load determined from biomarkers measured in blood. Results: In this small sample, bounce-back resilience and allostatic load level had a significant negative correlation, while ad­aptation resilience and allostatic load were slightly correlated, but the association was not statistically significant. Sixty-six percent of participants reported that they were able to adapt and 40% reported they were able to bounce back. Higher income and lower PSA level were significantly correlated with greater adaptation resilience. Minor­ity men were significantly more likely than non-minority men to report that they are able to bounce back. Married men were also significantly more likely than unmar­ried men to report that they were able to bounce back. Conclusion: It may be important to target resiliency training programs to Veterans based on their social determinants and to examine the effects of these programs on allostatic load. Ethn Dis. 2020;30(Suppl 1):177-184; doi:10.18865/ed.30.S1.177

Despite higher incidence and mortality of breast cancer among younger Black women, genetic testing outcomes remain severely understudied among Blacks. Past research on disclosure of genetic testing results to family members has disproportionately focused on White, educated, high socioeconomic status women. This study addresses this gap in knowledge by assessing (1) to whom Black women disclose genetic test results and (2) if patterns of disclosure vary based on test result (e.g., BRCA1/2 positive, negative, variant of uncertain significance [VUS]). Black women (N=149) with invasive breast cancer diagnosed age ≤50 years from 2009–2012 received free genetic testing through a prospective, population-based study. At 12 months post-testing, women reported with whom they shared their genetic test results. The exact test by binomial distribution was used to examine whether disclosure to female relatives was significantly greater than disclosure to male relatives, and logistic regression analyses tested for differences in disclosure to any female relative, any male relative, parents, siblings, children, and spouses by genetic test result. Most (77%) women disclosed their results to at least one family member. Disclosure to female relatives was significantly greater than disclosure to males (p0.12). Results suggest that in Black families, one benefit of genetic testing – to inform patients and their family with cancer risk information – is not being realized. To increase breast cancer preventive care among high-risk Black women, the oncology care team should prepare Black BRCA1/2 positive women to share genetic test results with family members and, in particular, their daughters.

A cancer diagnosis can upend work and family life, leading patients to reallocate resources away from essentials such as food. Estimates of the percentage of people navigating a cancer diagnosis and food insecurity range between 17% and 55% of the cancer patient population. The complexity of addressing food insecurity among those diagnosed with cancer during different phases of treatment is multifactorial and often requires an extensive network of support throughout each phase. This commentary explores the issue of food insecurity in the context of cancer care, explores current mitigation efforts, and offers a call to action to create a path for food insecurity mitigation in the context of cancer. Three programs that address food insecurity among those with cancer at various stages of care are highlighted, drawing attention to current impact and actionable recommendations to make programs like these scalable and sustainable. Recommendations are grounded in the National Academies of Sciences, Engineering, and Medicine social care framework through 5 essential domain areas: awareness, adjustment, assistance, alignment, and advocacy. This commentary seeks to highlight opportunities for the optimization of cancer care and reframe food access as an essential part of treatment and long-term care plans.

BackgroundAfrican American (AA) prostate cancer (PCa) appears uniquely sensitive to 1α,25(OH)2D3 signaling, compared to European American (EA) PCa, but the extent and impact of vitamin D receptor genomic functions remain poorly defined.ResultsA panel of EA and AA prostate epithelial cells (EA: HPr1-AR, LNCaP, AA: RC43N, RC43T, RC77N, RC77T) were analyzed with RIME to reveal the cell-specific composition of the VDR- complex. 1α,25(OH)2D3-dependent ATAC-Seq revealed the greatest impact on nucleosome positioning in RC43N and RC43T, with gain of nucleosome-free at enhancer regions. VDR ChIP-Seq identified stronger and more frequent VDR binding in RC43N and RC43T that was enriched for a larger and distinct motif repertoire, than EA cells. VDR binding significantly overlapped with core circadian rhythm transcription factors in AA cell line models. RNA-Seq also revealed significantly stronger 1α,25(OH)2D3 dependent VDR transcriptional responses enriched for circadian rhythm and inflammation networks in AA cells. Whilst RC43N was most responsive, RC43T displayed distorted responses. Significantly reduced BAZ1A/SMARCA5 in AA PCa samples was identified, and restored BAZ1A expression uniquely and significantly increased 1α,25(OH)2D3-regulated VDR targets in AA cells. These VDR- dependent cistrome-annotated genes were also uniquely and most significantly identified in three cohorts of AA PCa patients.ConclusionThese data suggest VDR transcriptional control in the prostate is more potent and dynamic in AA men, and primed to govern inflammatory and circadian pathways. Reduced BAZ1A/SMARCA5 expression and/or reduced environmentally-regulated serum vitamin D3 levels suppress these actions. Therefore, the VDR axis lies at the cross-roads of biopsychosocial processes including stress responses, access to quality early detection and treatment, social determinants and that collectively contribute to PCa health disparities.

Introduction The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides free breast cancer screening, case management, patient navigation, and connection to treatment for medically underserved and economically-disadvantaged women aged 40–64 years. The aim of this study was to identify differences in predictors of survival between all women diagnosed with breast cancer in South Carolina versus those enrolled in the SC NBCCEDP Methods We established a retrospective cohort of breast cancer patients diagnosed from 2004 to 2015 using the South Carolina Central Cancer Registry. Sociodemographic (e.g., race, age) and clinical variables were abstracted from the registry. We linked registry data to county-level variables to determine levels of social deprivation and residence in a health care professional shortage area using the Robert Graham Center’s Social Deprivation Index (SDI) and the Health Provider Shortage Area (HPSA) designation. Potential exposure variables (e.g., SDI, hormone receptor status, age, HER2 receptor status, time to first treatment, region, insurance status, cancer stage, year of diagnosis, rurality, NBCCEDP enrollment, race, marital status, cancer grade, HPSA designation) were entered into a Cox proportional hazard model to identify significant predictors of survival. The multivariable model utilized a backward elimination process to obtain the best fitting model at a p-value Citation Format: Oluwole A. Babatunde, Whitney E. Zahnd, Eric Adjei Boakye, Melanie S. Jefferson, Nosayaba Osazuwa-Peters, Chanita Hughes Halbert, Swann A. Adams. Statewide variability in predictors of survival among geographically and racially diverse breast cancer cohorts [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 C072.

The purpose of this study was to examine the association between neighborhood social deprivation and individual-level characteristics on breast cancer staging in African American and white breast cancer patients. We established a retrospective cohort of patients with breast cancer diagnosed from 1996 to 2015 using the South Carolina Central Cancer Registry. We abstracted sociodemographic and clinical variables from the registry and linked these data to a county-level composite that captured neighborhood social conditions—the social deprivation index (SDI). Data were analyzed using chi-square tests, Student’s t-test, and multivariable ordinal regression analysis to evaluate associations. The study sample included 52,803 female patients with breast cancer. Results from the multivariable ordinal regression model demonstrate that higher SDI (OR = 1.06, 95% CI: 1.02–1.10), African American race (OR = 1.35, 95% CI: 1.29–1.41), and being unmarried (OR = 1.17, 95% CI: 1.13–1.22) were associated with a distant stage at diagnosis. Higher tumor grade, younger age, and more recent year of diagnosis were also associated with distant-stage diagnosis. As a proxy for neighborhood context, the SDI can be used by cancer registries and related population-based studies to identify geographic areas that could be prioritized for cancer prevention and control efforts.

An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses, however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.

Lung cancer continues to be one of the leading causes of racial disparities in cancer morbidity and mortality among adults in the United States. Over the past 20 years, efforts to address disparities in lung cancer outcomes have focused on describing racial/ethnic differences in smoking behaviors and cessation outcomes. Other research has compared racial/ethnic groups in psychosocial and geographic risk factors for smoking and barriers to cessation; self-reported perceptions of stress and neighborhood deprivation have emerged as critical determinants of persistent tobacco use and predictors of relapse in disparity populations. Considerable investments have also been made to develop novel approaches for detecting lung cancer early and therapeutic strategies for treating this disease; lung cancer screening with LDCT now has a Grade B recommendation from the US Preventive Services Task Force and screening guidelines have been revised recently to be better aligned with the smoking behaviors and disease risk profiles among smokers from disparity populations. The demonstrated ability of LDCT to reduce lung cancer mortality is a significant clinical and public health advancement because it is the only evidence-based approach for detecting lung cancer at an early stage when treatment is most likely to be curative. However, several studies have demonstrated that patients from disparity populations have reduced uptake of cancer control strategies such as LDCT because of unmet social needs and risk factors; thus, revising lung cancer screening guidelines to be more inclusive may be necessary but not sufficient for improving access among disparity populations. The purpose of this presentation is to describe the goals and objectives for translational studies that are now being conducted to enhance equity in lung cancer outcomes among disparity populations and to identify priorities for future research in lung cancer equity. Citation Format: Chanita Hughes-Halbert. Translational issues in lung cancer disparities: A vision for cancer equity [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 SY30-01.

Black women are overrepresented among premenopausal breast cancer (BC) survivors. These patients warrant genetic testing (GT) followed by risk-reducing behaviors. This study documented patterns and predictors of cancer risk-management behaviors among young black BC survivors after GT. Black women (n = 143) with a diagnosis of BC at the age of 50 years or younger received GT. At 1 year after GT, participants reported receipt of risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, mammogram, breast magnetic resonance imaging (MRI), CA125 test, and transvaginal/pelvic ultrasound. Logistic regression was used to examine predictors of BC risk management (risk-reducing mastectomy or breast MRI) and ovarian cancer risk management (risk-reducing salpingo-oophorectomy, CA125 test, or transvaginal/pelvic ultrasound). Of the study participants, 16 (11%) were BRCA1/2-positive, 43 (30%) had a variant of uncertain significance, and 84 (59%) were negative. During the 12 months after GT, no women received risk-reducing mastectomy. The majority (93%) received a mammogram, and a smaller proportion received breast MRI (33%), risk-reducing salpingo-oophorectomy (10%), CA125 test (11%), or transvaginal/pelvic ultrasound (34%). Longer time since the BC diagnosis predicted lower likelihood of BC risk management (odds ratio [OR] 0.54). BRCA1/2 carrier status (OR 4.57), greater perceived risk of recurrence (OR 8.03), and more hereditary breast and ovarian cancer knowledge (OR 1.37) predicted greater likelihood of ovarian cancer risk management. Young black BC survivors appropriately received mammograms and ovarian cancer risk management based on their BRCA1/2 test result. However, the low usage of MRI among BRCA1/2 carriers contrasts with national guidelines. Future research should examine barriers to MRI among black BC survivors. Finally, modifiable variables predicting risk management after GT were identified, providing implications for future interventions.