American Cancer Patients Research Articles

Disparities within luminal breast cancer: Clinical and molecular features of African American and non-Hispanic white patients.

1009 Background: African American breast cancer patients (AA) are diagnosed younger, have more high-risk features, and poorer clinical outcomes than non-Hispanic White patients (NHW), despite similar treatments. Although comorbidities such as obesity and metabolic syndrome may contribute to differences, ancestry-specific factors and effects of structural violence that disproportionately afflict AA individuals may influence tumor biology and outcomes. We previously reported differentially expressed genes (DEGs) associated with tumor aggressiveness in Basal tumors from AA compared with NHW (Sharma et al., 2020). Here, we compare DEGs in luminal tumors between AA and NHW. Methods: The prospective, observational FLEX study (NCT03053193) includes stage I-III breast cancer patients who receive 70-gene signature (MammaPrint/MP)/80-gene signature (BluePrint/BP) testing and consent to full transcriptome and clinical data collection. AA (n=364) and NHW (n=400, random selection) with BP luminal tumors, enrolled from 2017 to present, were included. Race/ethnicity was self-reported. AA were younger than NHW (mean, 59 vs. 62 years, p=0.001); thus, an age-matched subset (n= 360 AA, NHW) was compared. Differential gene expression analysis was performed with R limma package. Comparisons were made between AA and age-matched or randomly selected NHW in: (1) all, (2) luminal A, (3) luminal B, and (4) luminal B, obese. DEGs with FDR<0.05 were significant. Different fold change (FC) thresholds were evaluated. Results: Compared with age-matched NHW, AA were similar in menopausal status, T stage, grade, and tumor type; obesity, T2DM status, and nodal stage were significantly different ( p<0.01). Tumors from AA were more often MP high risk ( p<0.001), regardless of age matching. Luminal B AA vs. age-matched NHW comparison resulted in more DEGs (n=1070) than other comparisons; however, most were FC<2. Notably, 5/6 DEGs ( PSPH, NOTCH2NL, POLR1A, MAP1LC3P and RPS26P10) in basal tumors (Nunes et al. 2019) were also identified here. Of 9 DEGs (FC>1.7) in the luminal B age-matched comparison, 2 ( PSPH and LINC01139) were also found in the luminal B, obese subset. Consistently upregulated DEGs in AA were associated with metabolism, translation, and cellular stress response pathways. Conclusions: We found significant transcriptomic differences between luminal tumors from AA and NHW, when controlling for age, obesity, and genomic classification. A subset of DEGs in luminal B tumors were consistent with those in Basal tumors, suggesting that similar race-associated factors drive DEGs regardless of tumor subtype. DEGs that may be unique to AA luminal tumors were also found. This study suggests that some biological differences in breast tumors may result from patient ancestry or shared adverse socioeconomic exposures and underscores the need for inclusion of diverse patient groups in clinical trials. Clinical trial information: NCT03053193.

Genomic risk classification by the 70-gene signature and 21-gene assay in African American early-stage breast cancer patients.

e12568 Background: Genomic risk of recurrence assays provide prognostic information that aids treatment recommendations for patients with early breast cancer (EBC). The 70-gene signature (MammaPrint/MP) and the 21-gene assay (Oncotype DX/ODX) were both validated by large prospective, randomized clinical trials. Previous studies have directly compared the performance of these assays, with moderate discordance widely observed. Recent work showed poor prognostic performance of the ODX in African American (AA) EBC patients (Hoskins et al., 2021). Here, we compare the concordance of two genomic tests in an AA cohort. Methods: This retrospective analysis included a subset of self-reported AA patients from the prospective, observational PROMIS (n = 66, NCT01617954) and FLEX (n = 29, NCT03053193) registry trials, for whom both MP and ODX RS results were available. Patients were enrolled from 2012 to present. The PROMIS trial enrolled patients with intermediate ODX RS (18-30). MP results were obtained from standard testing performed centrally by Agendia, Inc. (Irvine, CA); ODX testing was performed by Genomic Health, Inc. (Redwood City, CA) and results were collected from patient case report forms. Results: AA patients (n = 95) included in this sub-analysis were 77% post-menopausal with a median age of 60 years. 28% of patients were aged ≤ 50 years. Of patients with metabolic data (n = 49), 63% were obese by body mass index (BMI > 30), and 23% had type 2 diabetes mellitus (T2DM). Tumors were predominantly invasive ductal carcinoma (82%), T1 (73%), grade 2 (53%), ER+ (99%), HER2-negative (94%), lymph node-negative (86%), and MP High Risk (66%). By ODX clinical RS, 17% of tumors classified as low (0-17), 80% intermediate (18-30), and 3% high (31-100) risk. As expected, the large intermediate RS group reflects the inclusion of PROMIS patients. By TAILORx RS ranges, 76% of tumors were low risk (≤25). Of these, 61% (n = 44/72) classified as MP High Risk. Notably, 62% (n = 41/66) of tumors with TAILORx intermediate RS (11-25) were MP High Risk. Conclusions: The overall discordance between MP and ODX was 51% in these AA patients. Discordance was more frequent (61%) in ODX low risk (RS≤25) cases. Notably, of tumors with TAILORx intermediate RS (11-25), the majority (62%) classified as MP High Risk. Combined with previously published data in AA patients (Nunes et al., 2016), this results in a total of 57% (n = 52/91) of ODX low RS (≤25) tumors classified as MP High Risk. Recent data indicate that AA patients who receive a low (≤10 or ≤25) or intermediate RS (11-25) have higher recurrence rates and lower survival than White/Caucasian EBC patients with the same RS. In the current study, clinical outcomes are forthcoming; however, these data suggest the majority of AA patients are more likely to receive a MP High Risk result, which may capture the diversity of pathways driving tumor metastasis. Clinical trial information: NCT01617954, NCT03053193.

Physician concern about delaying lung cancer treatment while awaiting biomarker testing: Results of a survey of U.S. oncologists.

9067 Background: With rapid advancements in biomarker testing informing lung cancer treatment decisions, clinicians are challenged to maintain knowledge of who, what and when to test and how to treat based on test results. An ASCO taskforce including representatives from the American Cancer Society National Lung Cancer Roundtable and patient advocates conducted a study to assess biomarker testing and treatment practices for patients with advanced non-small cell lung cancer (aNSCLC) among U.S. oncologists. Methods: A survey was sent to 2374 ASCO members – lung cancer specialists and general oncologists. Eligibility required treating ≥1 lung cancer patient/month. Proportions were estimated across groups and compared using chi-square tests. Results: 170 responses were analyzed. 59% of respondents work at an academic center (i.e., have a fellowship program), while 41% work at a community (non-academic hospital/health system/private practice). Nearly all (98%) believe biomarker results should be received within 1 or 2 weeks of ordering, yet 37% wait an average of 3 or 4 weeks for results. Of respondents who usually wait 3 or 4 weeks, 37% initiate a non-targeted systemic treatment while waiting. Respondents from community practices were more likely to initiate non-targeted systemic treatment if results were not available after 2 weeks (59% compared to 40% of academic respondents; p = 0.013). ). When asked about reasons for not testing, respondents <5 years since training were more likely to report that delaying treatment while waiting for results was always/often a concern compared to those >6 years from training (41% vs 19%). Respondents reported high testing rates in both non-squamous and squamous aNSCLC. Roughly equal representation of generalists/specialists and academic/community respondents helps mitigate potential concerns about external validity. Conclusions: Respondents indicated that treatment decisions are impacted by delays in biomarker test results. Clinicians should be informed about when it is safe and appropriate to defer treatment while biomarker testing is pending. Respondents suggest that diagnostic biomarker testing companies should strive to expedite results.[Table: see text]

Impact of medical mistrust (MM) on perceptions of tumor genomic profiling (TGP) among African American (AA) cancer patients: Application of perceptual mapping (PM).

e22527 Background: TGP is widely used to identify targetable mutations for precision cancer treatment and clinical trials. Many patients have poor understanding of TGP and are unaware of possible secondary hereditary risks. Lack of clarity regarding the relevance of informed consent and genetic counseling further magnify risks for patients. AA patients have lower genetic knowledge and health literacy and higher MM than Caucasian patients, making them especially vulnerable in the clinical setting. Perceptions of TGP in AA cancer patients have not been well-characterized. Methods: 120 AA pts from 1 suburban and 1 urban site (Fox Chase Cancer Center[FCCC] and Temple University Hospital[TUH]) were surveyed. A k-means cluster analysis using a modified MM scale was conducted; chi-square analysis assessed demographic differences. Perceptual mapping (PM)/multidimensional scaling and vector modeling was used to create 3-dimensional maps to study how TGP barriers/facilitators differed by MM group and how message strategies for communicating about TGP may also differ. Results: Data from 112 analyzable patients from FCCC (55%) and TUH (45%) were parsed into less MM (MM-L, n = 42, 37.5%) and more MM (MM-H, n = 70, 72.5%) clusters. MM-L and MM-H clusters were demographically indistinct with no significant associations by sex (p = 0.49), education (p = 0.3), income (p = 0.65), or location (p = 0.43); only age was significant (older = higher MM, p = 0.006). Patients in the MM-H cluster reported higher concerns about TGP, including cost (p < 0.001), insurance discrimination (p < 0.001), privacy breaches (p = 0.001), test performance/accuracy (p = 0.001), secondary gain by providers (p < 0.001) and provider ability to explain results (p = 0.04). Perceptual mapping identified both shared and contrasting barriers between MM clusters (Table). Conclusions: More than 2/3 of AA patients comprised a MM-H cluster. Communication strategies should focus on concerns about family and how to discuss TGP with an oncologist. PM can identify distinct and shared information needs of vulnerable populations undergoing TGP. [Table: see text]

Genomic aberrations in African American patients with solid tumors: A comparative institutional study.

e15086 Background: Genomic mutations play an important role in cancer pathogenesis and can be used as targeted agents for treatment. Cancer related biomarkers in body fluids and tissues are being used to identify specific target genes. They also help in predictive and prognostic assessment related to the disease. Various platforms like guardant 360, foundation act, oncotype are commercially available. Specific genomic aberrations have enhanced the field of Precision Medicine in individualizing treatment protocols. Methods: Prospective data was collected from 45 African American patients at our institution using the commercially available Genomic Enabled Medicine ExTra cancer panel (Ashion Analytics). Sample include 18 types of cancer (10 breast, 9 colorectal, 5 endometrium, 4 prostate, 3 uterine, 2 cervical, 1 pancreas, 1 gallbladder, 1 melanoma, 1 larynx, 1 gastric, 1 carcinoid, 1 carcinosarcoma, 1 lymphoma, 1 ovary, 1 bladder, 1 thyroid). Both tumor and normal DNA were collected from year 2019 through 2020. For comparison, clinical and genomic, The Cancer Genome Atlas (TCGA) data for 1,065 African American adults with solid tumors were downloaded from the NCI Genome Data Common portal. The two data sets were eventually compared for identifying common genetic mutations and possible new targets for cancer management. Results: Of the 45 patients, 38 patients (84%) had at least one genomic alteration, and 38 known driver mutations were identified. Their median age was 56 years (range, 37 – 94). TP53 mutations were most common, identified in 44% of patients versus 37% in African Americans in TCGA. PIK3CA and KRAS mutations were next most common (22% and 20%, respectively) compared to TCGA African American samples (13% and 12%, respectively). The most frequent mutations on PIK3C were H1047R in 4 patients (8.8%), followed by E545K in 3 patients (6.6%). Oncogenic mutations were observed in APC, PTEN, ARID1A, FBXW7, NF1, PIK3R1, RNF43, ATM, CCNE1. Conclusions: In our study, we found higher prevalence of oncogenic driver gene mutations (including TP53, PIK3CA, KRAS, APC, PTEN, ARID1A) in African American cancer patients compared to TCGA African American cancer patients. It is important to note that high percentage of our patients had actionable oncogenic drivers that may be useful in treatment decision-making. Our aim is to continue to build on our database on African American patients for identifying specific and common gene mutations to enhance development of targeted agents.

Healthcare professionals’ perspectives on unique communication and care needs for Chinese American cancer patients.

e24122 Background: Effective clinician-patient discussions of cancer diagnoses and prognoses are essential to enhance health outcomes in diverse oncology populations. To provide guidance on communication preferences and needs among Chinese Americans, one of the fastest growing yet understudied ethnic groups in the United States, we explored considerations and observations from healthcare providers experienced in caring for this oncologic population. Methods: In this inductive, emergent qualitative study, we completed 20 semi-structured virtual interviews with providers from assorted healthcare disciplines with experience caring for Chinese American cancer patients in Boston’s Chinatown. Responses were systematically collected and analyzed using open and focused coding, constant comparative methods, and thematic analysis. Results: Twenty healthcare professionals with experience working with the Chinese American patients were interviewed including medical oncologists, radiation oncologists, primary care physicians, nurses, nurse practitioners, social workers, case managers, patient navigators and dietitians. Fifteen were female, 5 were male, and 11 participants self-identified as Asian. Six key themes were identified: (1) Discussing cancer diagnoses and prognoses is taboo and often avoided by Chinese Americans in family, community, and healthcare settings. (2) A cancer diagnosis may be considered a death sentence by Chinese Americans, regardless of cancer location or stage. This could be related to the meaning implied by direct translation of the word “cancer.” (3) In settings where cancer diagnoses and prognoses are discussed, Chinese American patients often prefer indirect communication approaches including use of expressions such as “tumor,” “mass,” or “illness” to avoid the use of the word “cancer.” (4) The family centered role in medical decision making for Chinese American cancer patients and the preference of some family units to protect the patient from their diagnoses present unique challenges in the context of standard care. (5) Obtaining a detailed psychosocial history is important to guide communication approaches, as patient characteristics like age, generation since immigration, and education play a foundational role in communication preferences. (6) Karma and nutritional beliefs should be considered and addressed in oncologic care, as they play a critical role in health and disease management for Chinese American cancer patients. Conclusions: Further exploration of these insights and confirmation of their accuracy by discussing directly with Chinese American patients is imperative. If these findings are corroborated through further investigation, this knowledge can be used develop educational tools and implement clinical practice changes to enhance care outcomes and communication with Chinese American cancer patients.

Life expectancy in metastatic prostate cancer patients according to racial/ethnic groups.

To quantify the magnitude of differences between observed overall survival and respective, age-adjusted Social Security Administration life tables-derived life expectancy in Caucasian, African American, Hispanic/Latino and Asian metastatic prostate cancer patients. Furthermore, to test for differences in cancer-specific mortality and other-cause mortality according to race/ethnicity. We relied on the 2004-2006 Surveillance, Epidemiology and End Results database to identify Caucasian, African American, Hispanic/Latino and Asian metastatic prostate cancer patients. Social Security Administration life tables were used to compute 10-year life expectancy for comparisons with observed overall survival. Poisson regression plots showed cancer-specific mortality relative to other-cause mortality for each race/ethnicity. A total of 2574 (64.2%) patients were Caucasian, 753 (18.8%) were African American, 453 (11.3%) were Hispanic/Latino and 227 (5.7%) were Asian, respectively. The median age at diagnosis was 72years in Caucasian patients, 68years in African American patients, 70years in Hispanic/Latino patients and 72years in Asian patients. Observed overall survival rates were always lower compared with respective predicted life expectancy. The magnitude of the difference between observed overall survival and predicted life expectancy at 10years was highest in African American patients (-52.2%), followed by Caucasian patients (-48.3%), Hispanic/Latino patients (-46.1%) and Asian patients (-37.4%). African American patients showed the highest cancer-specific mortality rates (71.1%) and second-highest other-cause mortality rates (17.4% vs highest 18.4% in Caucasian patients), despite having the youngest age at diagnosis. Asian patients showed the lowest cancer-specific mortality rates (65.5%, P<0.0001) and lowest other-cause mortality rates (13.3%, P=0.04), despite having the oldest age at diagnosis. Despite having the youngest age at diagnosis, African American patients show the least favorable survival profile in metastatic prostate cancer. Conversely, Asian patients show the most favorable survival profile in metastatic prostate cancer, despite having the oldest age at diagnosis.

The importance of community and culture for the recruitment, engagement, and retention of Chinese American immigrants in health interventions.

Chinese Americans experience cancer health disparities throughout the entire cancer continuum. Yet, they remain underrepresented in health research in part due to barriers in recruitment, engagement, and retention. This paper describes the strategies that we devised, by drawing upon our experiences with conducting two culturally sensitive cancer intervention studies, to help researchers improve their recruitment and retention rates of Chinese Americans in health research and address the gap in knowledge on intervention research with this population. The first study assessed the efficacy, adoption, and impact of an intervention, delivered by community health workers, to improve adherence to recommended stomach cancer prevention guidelines for at-risk Chinese Americans. The second study evaluated the feasibility and preliminary efficacy of a culturally adapted version of the Expressive Helping intervention for Chinese American cancer patients and survivors. Our main recruitment strategies revolved around building community relationships, developing culturally sensitive materials, and establishing good first impressions with participants. Our main engagement and retention strategies focused on attending to cultural sensitivity, fostering relationships, and using technology. Harnessing the community's inherent strengths and prioritizing cultural understanding is crucial for culturally sensitive health research with Chinese Americans.

Exploratory Study of Advance Care Discussions Among Chinese American and White Stage IV Cancer Patients at an American Tertiary Medical Center.

Timely advance care discussions are essential components of quality care for diverse populations; however, little is known about these conversations among Chinese American cancer patients. This exploratory study describes differences in advance care discussions and planning between Chinese American and White advanced cancer patients. We collected data for 63 Chinese American and 63 White stage IV cancer patients who died between 2013 and 2018. We compared: frequency and timing of prognosis, goals of care (GOC), and end-of-life care (EOLC) discussions in the final year of life; family inclusion in discussions; healthcare proxy (HCP) identification; do not resuscitate (DNR) order, do not intubate (DNI) order, and other advance directive (AD) completion. We did not conduct statistical tests due to the study's exploratory nature. Among Chinese American and White patients, respectively, 76% and 71% had prognosis, 51% and 56% had GOC, and 89% and 84% had EOLC discussions. Prognosis, GOC, and EOLC discussions were held a median of 34.0, 15.5, and 34.0 days before death among Chinese American and 17.0, 13.0, and 24.0 days before death among White patients. Documentation rates among Chinese American and White patients were 79% and 76% for DNRs, 81% and 71% for DNIs, 79% and 81% for HCPs, and 52% and 40% for other ADs. Findings suggest that Chinese Americans had similar rates of advance care discussions, completed conversations earlier, and had similar to higher rates of AD documentation compared to White patients. Further studies are needed to confirm our preliminary findings.

Perspectives of multisectoral community stakeholders on Arab American cancer patients' needs and suggested interventions.

Multilevel barriers can arise after a cancer diagnosis, especially in underserved racial/ethnic minority patient populations, raising the need for diverse and contextually adapted interventions. However, limited data exists on Arab American (ArA) cancer patients' needs, partly due to their racial/ethnic misclassification as Whites. This study leveraged the perspectives of cancer survivors and community stakeholders (i.e., healthcare and community leaders) to identify ArA cancer patients' needs, as well as their preferred intervention strategies to address them. Using a hybrid inductive-deductive content analysis approach, we analyzed qualitative data from interviews with 18 ArA community stakeholders recruited through community partners in Chicago. Participants associated cancer stigma to ArA patients' concealment of their diagnosis and aversion to cancer support groups. Economic and language barriers to treatment were emphasized. A lack of resources for ArA cancer patients was also noted and was partly attributed to their misclassification as White. In response to these needs, participants suggested peer mentorship programs to overcome privacy concerns, hospital-based patient navigation to address language and economic barriers in healthcare, diversification of the healthcare workforce to overcome language barriers, and community coalitions to recognize ArA as an ethnic group and increase cancer support resources. Such advocacy will be essential to accurately characterize patients' cancer burden and obtain funding to support community programs and resources. Our findings suggest that multilevel interventions at the patient, healthcare, and community levels are needed to address ArA cancer patients' needs.

An Exploration of Suffering and Spirituality Among Older African American Cancer Patients as Guided by Howard Thurman's Theological Perspective on Spirituality.

The use of the religious experience to mitigate suffering within the context of a cancer diagnosis and treatment is poorly understood. Specifically, in this article, we explore suffering and the religious experience using Howard Thurman's theological perspective. This perspective permits an exploration of the ways in which spirituality enables African American cancer patients to better manage suffering through: (1) a positive self-image as a child of God or the identification with the sufferings of Jesus; (2) seeking harmony in one's environment; (3) the use of spirituality as self-nourishment; and, (4) the perspective of suffering as sacrament. In this paper, we use the narratives of African American cancer patients to argue that these theological perspectives are indeed relevant to the relief of suffering among this population.

Exploratory Study Comparing End-of-Life Care Intensity between Chinese American and White Advanced Cancer Patients at an American Tertiary Medical Center.

Background: Understanding ethnic disparities in end-of-life care (EOLC) intensity is central to improving outcomes for diverse populations. Although Chinese Americans represent one of the fastest growing ethnic groups in the United States, little is known about their EOLC intensity.Objective: To explore differences in indicators of high-intensity EOLC in the final 30 days of life, place of death, and hospice utilization between Chinese American and White advanced cancer patients.Methods: In this exploratory review, we collected data on 48 Chinese American and 48 White stage IV solid tumor patients who died during 2013–2018. Indicators of high-intensity care from the final 30 days of life included ≥2 hospital, ≥1 intensive care unit (ICU), and/or ≥2 emergency department admissions; cardiopulmonary resuscitation administration and mechanical ventilation (MV); place of death; and whether patients were on hospice at death.Results: Among Chinese American and White patients, respectively, 49% and 36% died in the hospital, 15% and 7% died in the ICU, 17% and 8% received MV, and 6% and 13% had ≥1 hospital admission lasting >14 days. Seventeen percent of Chinese American and 43% of White patients died at home. Hospice enrollment was similar between groups. Seventeen percent of Chinese American and 8% of White patients died within 30 days of diagnosis.Conclusion: Results suggest that fewer Chinese Americans died at home, whereas more died in the ICU, received MV, and died within 30 days of cancer diagnosis, indicating possible disparities in EOLC. Further studies are needed to explore findings from this exploratory investigation.

Abstract PS7-68: Racial disparities within basal-type breast cancer: Clinical and molecular features of African American and Caucasian obese patients

Abstract Background: African American breast cancer patients (AA) are diagnosed at a younger age and present more frequently with triple-negative/Basal tumors than Caucasian American patients (CA). High prevalence of obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome in AA may confound attempts to evaluate the influence of race on gene expression. Previously we showed that differentially expressed genes (DEGs) between AA and CA within the Basal subtype were related to metabolism, translation, and cell signaling pathways (Nunes et al. 2019). However, AA had higher obesity and T2DM rates than CA, and we were unable to distinguish between the influence of metabolic factors and race. In the current analysis, we aim to dissect these factors by comparing clinical and molecular features of Basal-type breast tumors in obese AA and CA. Methods: The prospective, observational FLEX Registry (NCT03053193) includes stage I-III breast cancer patients who receive 70-gene signature (MammaPrint, MP)/80-gene signature (BluePrint, BP) testing and consent to full transcriptome and clinical data collection. This interim substudy included 50 AA and 96 CA (n=146), enrolled from 2017 to present, all obese by body mass index (BMI, ≥30) and whose tumors were MP High Risk and BP Basal subtype. AA were significantly younger (mean, 55 years) than CA (mean, 60 years, p=0.02); thus, an age distribution-matched subset (n=49 AA, n=49 CA) was added for comparison. Gene expression data were quantile normalized using R limma package; DEGs were compared between groups in the following: (1) all AA (n=50) and CA (n=96), (2) AA and 3 random selections of CA (n=50 pairs), and (3) age-matched AA and CA (n=49 pairs). Results: Clinical factors, including tumor stage, nodal stage, and T2DM status were similar between AA and CA, regardless of age-matching. Most tumors were T1/2 (83% AA, 88% CA) and negative for nodal involvement (77% AA, 68% CA). 94% of tumors from AA and 74% of tumors from CA were grade 3 (p=0.17). Notably, 32% of tumors from AA and 46% of tumors from CA were ER+ by immunohistochemistry. Age-matched AA and CA had a 20% rate of T2DM. 152 DEGs were significant (adjusted p&amp;lt;0.05) in at least one comparison, with 115 genes more highly expressed in AA and 37 genes more highly expressed in CA. Across all comparisons, 6 genes were consistently more highly expressed in AA: PSPH, NOTCH2NL, POLR1A, AC069240.1, ORAI1, and RPS26P10. Except ORAI1, these genes were also found in the previous comparison between Basal-type AA and CA, and the current analysis confirmed 11/16 DEGs previously reported (Nunes et al. 2019). Genes more highly expressed in AA are associated with transcription, angiogenesis, and Notch signaling pathways, as well as breast cancer aggressiveness and treatment resistance. Conclusions: Higher prevalence of obesity/T2DM in AA has been proposed as a key factor to explain racial disparities in breast cancer incidence and prognosis, but the current results suggest that race may influence DEGs more than differences in tumor subtype, age, or metabolic factors. This comparison also emphasizes the importance of matched clinical features for DEG analysis and suggests disparities in AA beyond those attributable to clinical differences within the population. DEGs in AA suggest upregulation of Notch-associated aggressiveness, which may be particularly relevant under hypoxic conditions (e.g., obesity), and pathways associated with stemness, metastasis, and chemotherapy resistance. Notch pathway also interacts with key oncogenic pathways, and future studies will reveal the molecular networks underlying racial disparity in AA and CA breast cancer patients. Citation Format: Dipali Sharma, Lisa E. Blumencranz, Heather M. Kling, Sahra Uygun, Sarah Untch, William Audeh, Jennifer A. Crozier, Mehran Habibi, Raquel Nunes. Racial disparities within basal-type breast cancer: Clinical and molecular features of African American and Caucasian obese patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-68.

Prevalence of Psychological Symptoms in Community-Dwelling Chinese American Patients with Chronic Cancer Pain.

Cancer is common among older Chinese American immigrants. Psychological distress may be associated with cancer pain, yet prior studies have not examined this relationship. We conducted a secondary analysis of 514 Chinese Americans with cancer-related pain. Patients completed validated questionnaires, including the Chinese Health Questionnaire-12 (CHQ-12). Analyses evaluated associations among sociodemographics, acculturation, psychological distress, and pain variables. Most patients had low acculturation and socioeconomic levels. Overall, 51.9% of patients reported moderate-severe psychological distress, 35.8% reported worst pain intensity ≥7/10 over the previous week and 41.2% had high pain-related distress. Higher CHQ-12 scores were associated with younger age (β = -0.13); lower educational level (β = -0.12); birthplace in China (β = -0.18); lack of a caregiver (β = -0.10); higher worst pain intensity (β = 0.15); and higher pain-related distress (β = 0.28; all p < 0.05; R2= 0.23). Chinese American cancer patients with chronic pain experience high psychological distress, which is associated with pain characteristics and other social factors.

Geographic heterogeneity in the outcomes of patients receiving immune checkpoint inhibitors for advanced solid tumors: a meta-analysis.

BackgroundLittle is known about the effect of geographic location on efficacy of immune checkpoint inhibitors (ICI). We performed a systematic review and meta-analysis to assess the heterogeneity of ICI efficacy between different geographic locations.MethodsWe searched PubMed, EMBASE, and the Cochrane Library through October 2019 for phase III randomized controlled trials (RCT) that provided sufficient data for hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS) or progression-free survival (PFS) according to designated geographic region. We calculated pooled HRs and 95% CIs for North American, European and Asian cancer patients, and assessed data heterogeneity using subgroup and sensitivity analysis. The INPLASY registration number was INPLASY202050062.ResultsOf 10151 publications identified in our research, 17 RCTs including 7462 patients met our selection criteria. The pooled HRs for OS of North American, European and Asian patients were 0.67 (95% CI: 0.57 to 0.78), 0.72 (95% CI: 0.64 to 0.81), and 0.74 (95% CI: 0.66 to 0.84) respectively; the pooled HRs for PFS of North American, European and Asian patients were 0.58 (95% CI: 0.49 to 0.69), 0.61 (95% CI: 0.41 to 0.90), and 0.87 (95% CI: 0.38 to 1.99) respectively. Both anti-PD-1 inhibitors and anti-PD-L1 inhibitors showed clinical benefit in North American and European arms while anti-PD-L1 inhibitors failed to show benefit in Asian arms.ConclusionsOur meta-analysis indicates that the magnitude of benefit from ICI varies in North America, Europe, and Asia. Asian patients experience inferior outcomes compared to Western patients. Notably, anti-PD-L1 therapies do not result in survival improvements in Asian patients.

Randomized controlled trial of a breast cancer Survivor Stories intervention for African American women.

Video-based interventions hold promise for improving quality of life (QoL) among African American breast cancer patients. An interactive, cancer-communication intervention using African American breast cancer survivors' narratives was tested in a randomized controlled trial to determine whether viewing survivor stories improved newly diagnosed African American breast cancer patients' QoL. Participants were 228 African American women with non-metastatic breast cancer interviewed five times over two years; 120 controls received standard medical care, and 108 intervention-arm participants also received a tablet-computer with survivor stories three times in 12 months. Growth curve models were used to analyze differences between arms in change in eight RAND 36-Item Health Survey subscales, depressive symptoms, and concerns about recurrence. Additional models explored the effects of intervention usage and other intervention-related variables on QoL among patients in the intervention arm. Models showed no effect of study arm on QoL, depressive symptoms, or concerns about recurrence. Longer use of the intervention was associated with an increase in concerns about recurrence and decline in three QoL subscales: emotional wellbeing, energy/fatigue, and role limitations due to physical health. Although no significant impact of the intervention on QoL was observed when comparing the two study arms, in the intervention arm longer intervention use was associated with declines in three QoL subscales and increased concerns about recurrence. Women with improving QoL may have interacted with the tablet less because they felt less in need of information; it is also possible that encouraging patients to compare themselves to survivors who had already recovered from breast cancer led some patients to report lower QoL. Future work is warranted to examine whether adding different stories to this cancer-communication intervention or using stories in conjunction with additional health promotion strategies (e.g., patient navigation) might improve QoL for African American breast cancer patients.

MYC DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score.

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3′ UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: −14.74 to −0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10−4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.

Cancer stem cells: Culprits in endocrine resistance and racial disparities in breast cancer outcomes.

Breast cancer stem cells (BCSCs) promote endocrine therapy (ET) resistance, also known as endocrine resistance in hormone receptor (HR) positive breast cancer. Endocrine resistance occurs via mechanisms that are not yet fully understood. In vitro, in vivo and clinical data suggest that signaling cascades such as Notch, hypoxia inducible factor (HIF), and integrin/Akt promote BCSC-mediated endocrine resistance. Once HR positive breast cancer patients relapse on ET, targeted therapy agents such as cyclin dependent kinase inhibitors are frequently implemented, though secondary resistance remains a threat. Here, we discuss Notch, HIF, and integrin/Akt pathway regulation of BCSC activity and potential strategies to target these pathways to counteract endocrine resistance. We also discuss a plausible link between elevated BCSC-regulatory gene levels and reduced survival observed among African American women with basal-like breast cancer which lacks HR expression. Should future studies reveal a similar link for patients with luminal breast cancer, then the use of agents that impede BCSC activity could prove highly effective in improving clinical outcomes among African American breast cancer patients.

Abstract PO-129: High expression of MKK3 correlates with poor clinical outcomes in African American breast cancer patients

Abstract African American women experience a 2-fold higher incidence of triple-negative breast cancer (TNBC) and are 40% more likely to die from breast cancer than women of other ethnicities. Previous studies have revealed a higher frequency of inactivating mutations in multiple tumor suppressor genes in African American breast cancer patients as compared to White patients. However, the molecular bases for the survival disparity in breast cancer remain unclear, and no race-specific therapeutically actionable targets have been proposed. To address this clinical need, we took the computational systems biology approach to uncover new potentially druggable genes that contribute in poor clinical outcomes of African American breast cancer patients. Through a comprehensive analysis of gene expression and survival data determined for The Cancer Genome Atlas (TCGA) breast cancer patient cohort, we found that more than 30% of all protein-coding genes are differentially expressed in White and African American breast cancer patients. The cluster analysis of co- regulated genes combined with the pathway enrichment analysis revealed a strong association of genes upregulated in African American patients with major oncogenic processes including cell cycle regulation, immunodeficiency, and oxidative phosphorylation. We have further identified more than 30 genes whose overexpression correlates with worsened clinical outcomes of African American breast cancer patients but not White patients. Among those genes, the overexpression of mitogen-activated protein kinase kinase 3 (MKK3) has one of the most dramatic and race-specific impacts on the survival of African American TNBC patients. We found that MKK3 can promote the TNBC tumorigenesis in African American patients in part by activating the master regulator MYC through protein- protein interaction. Together, this study uncovered new genetic features and molecular mechanisms of breast cancer tumorigenesis. As one example, we discovered new functional connectivity between poor clinical outcomes of African American TNBC patients and activation of the MYC transcriptional program through MKK3 signaling. These findings may open new opportunities for clinical investigations to reduce the survival disparity in breast cancer. Citation Format: Xuan Yang, Mohamed Amgad, Lee A.D. Cooper, Yuhong Du, Haian Fu, Andrey A. Ivanov. High expression of MKK3 correlates with poor clinical outcomes in African American breast cancer patients [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-129.

Abstract IA45: Genomics contributors to tumor subtypes in African American prostate and breast cancer patients

Abstract African Americans suffer disproportionally in higher cancer incidence and worse overall survival in a number of cancer types. The reasons for the disparities are multifactorial and include differences in access to healthcare and lifestyle exposures, delayed disease diagnosis in socio-economically deprived communities, tumor biological differences, and factors related to genetics. Recent findings from multiple prostate and breast cancer genomics studies have identified subsets of ancestry associated genes that are associated with worse outcomes. Therefore, we will present an overview of these recent findings from our lab and others, specifically focusing on how these driver genes function a subset of tumors. Additionally, we will provide examples of how these ancestry-associated genes are integrated within regulatory networks, and discuss the possibility of ancestry specific subtypes promote aggressive disease in African American breast and prostate cancer patients. Citation Format: Clayton Yates. Genomics contributors to tumor subtypes in African American prostate and breast cancer patients [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA45.