bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B107: Race-specific gene expression patterns in triple-negative breast cancer (TNBC) cases
Authors: Martini Rachel , White Jason , Verma Akanksha , Elemento Olivier , Newman Lisa , Upender Manne , Yates Clayton , Davis Melissa
Published: September 2020

Historically, incidence rates of breast cancer (BC) have been higher among Caucasian (CA) women compared to African-American (AA) women, until convergence of these rates in the mid 2000s. Conversely, when accessing mortality rates among these women, AA women have reported higher rates of mortality from BC since the mid 1980s. Despite a decline in BC mortality over the past 30 years, the mortality rate of disease among AA women remains to be significantly higher than that of their CA counterparts. When molecular subtypes of BC are considered, prevalence of Triple-Negative BC (TNBC), the most aggressive subtype of BC, is found to be higher among AA women. TNBC prevalence on the global scale shows highest levels of TNBC across Africa, and higher rates can also be observed across the African diaspora. To address this, we sought out to identify race-specific differences among TNBC cases. We completed RNA sequencing on a cohort of 75 cases, where 42 of the cases were AA, and 33 were CA. The dataset was dichotomized by if the individuals had received neoadjuvant chemotherapy prior to surgery and specimen collection, where we had 60 treatment naïve cases (31 AAs and 29 CAs) and the remaining 15 had received neoadjuvant chemotherapy (residual tumors; 11 AAs and 4 CAs). We assessed self-reported race, ancestry estimation from matched DNA samples into and TNBC molecular subtyping from matched DNA samples into our DE gene expression analyses. Among treatment naïve tumors, we identified over 1000 genes that were significantly differentially expressed (DE) between race groups (p < 0.05). To further analyze our race-specific gene set, we used Ingenuity Pathway Analysis (IPA) to investigate relevant pathways and regulators specific to our gene set. Using the causal network analysis, we see that biological functions such as cellular organization and assembly show significant enrichment in our gene set, and that the NFkB complex is a top regulator predicted to be activated in our AA treatment naïve cases compared to CAs. For those individuals who had received neoadjuvant chemotherapy, we identified 13 genes that are significantly different between race groups, and these DE genes are distinct from those identified in our treatment naïve analyses.

Citation Format: Rachel Martini, Jason White, Akanksha Verma, Olivier Elemento, Lisa Newman, Manne Upender, Clayton Yates, Melissa Davis. Race-specific gene expression patterns in triple-negative breast cancer (TNBC) cases [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B107.
Abstract B113: Unique hormone receptor signatures of inflammatory breast cancer in a cohort of Puerto Rican women
Authors: Underill Zoe C , Rivera Mayra , Martinez Michelle M
Published: September 2020

Inflammatory breast cancer (IBC) is an uncommon although highly lethal form of breast cancer. Existing IBC research focuses mainly on United States or European populations, limiting current knowledge of patient profiles in Hispanic populations. Given the unique genetic admixture that exists in PR, we are interested in characterizing IBC within this population to broaden understanding of this disease. We designed a retrospective study which was deemed exempt by the UCC-IRB. A sample of breast cancer patient charts were reviewed at Manatí Medical Center and Pavia Hospital. Of these, 18 eligible subjects with a new primary diagnosis of IBC between 2012-2019 were identified and data was collected from oncologist and pathologist reports. On review, 78% of patients were negative for HER-2/neu receptor overexpression and there was a difference, although not statistically significant (p=0.09) compared to other receptor status. This result differs from other studied populations which place HER-2/neu positivity in the range of 36-60% for IBC. Interestingly, 36.4% expressed the particular signature (ER+, PR+, HER2/neu-) and 36.4% presented as triple negative for tumor markers (ER-, PR-, HER-2/neu-) on pathology review. Our data suggests that within the context of the population studied, IBC is less likely to express HER-2/neu receptor compared to IBC in other populations, and we identified two specific signatures that comprise the majority of the cases studied. To improve patient outcomes for IBC it is critical to have foundational understanding of the disease characteristics and course within a diverse group of patients. This study aims to set such a foundation within the population of PR. With this knowledge, further treatments can be tailored to meet the needs of unique or minority populations such as this one.

Citation Format: Zoe C Underill, Mayra Rivera, Michelle M Martinez. Unique hormone receptor signatures of inflammatory breast cancer in a cohort of Puerto Rican women [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B113.
Abstract B117: Body positivity after a double mastectomy
Authors: D'Agostino Chiara
Published: September 2020

A healthy body image after a traumatic double mastectomy is an important phase of survivorship. Part of the healing process in breast cancer is to learn to love one’s body again, with all its changes. Body Positivity After a Double Mastectomy explores a woman’s journey to body positivity despite her physical and emotional challenges.

Citation Format: Chiara D'Agostino. Body positivity after a double mastectomy [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B117.
Abstract B125: Molecular profiling basal 2 subtypes of triple-negative breast cancer cells and their response to histone deacetylase inhibitor
Authors: Lyn-Cook Beverly , Stovall Destiny , Word Beverly , Cotton Ebony , Hammons George
Published: September 2020

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer that often strikes young women, particularly minority women in their reproductive years. This cancer has a poor prognosis, mainly due to the lack of effective chemotherapeutic agents. Triple negative breast cancers present an additional problem, in that a histologically subtype can have molecularly different forms. Studies have shown that histological designated tumors yield different treatment results. Recently, molecular profiling of a patient’s tumor yielded detection of specific driver genes that resulted in the use of single or combination therapies targeting these driver genes. Basal 2 subtype is one of the most aggressive form of TNBC. This study examined the molecular profiles of two Basal 2 triple negative breast cancers representing two different African American women in response to treatment with vorinostat. Using a RT2 Profiler PCR gene expression array, vorinostat up-regulated 54 genes and downregulated 3 genes in HCC70 TNBC. In HCC1806 TNBC, 23 genes were upregulated and 38 downregulated. The most significant change in gene expression noted in HCC70 was in CCND2, which is hypermethylated in TNBC. Changes were also noted in SNA12, SERPINE, and TWIST. In HCC1806, significant changes in gene expression were noted in ABCB1, CCND2, CDKN1C and MMP9. These results clearly demonstrated that there is a differential response to a potential anti-tumor drug by different molecular subtypes. Up-regulation of CCND2 was observed in both basal 2 cell lines. CCND2 encodes cyclin D2 in which low expression is associated with poor prognosis. Understanding individual differences in cancer driver genes will greatly improve personalized medicine in TNBC.

Citation Format: Beverly Lyn-Cook, Destiny Stovall, Beverly Word, Ebony Cotton, George Hammons. Molecular profiling basal 2 subtypes of triple-negative breast cancer cells and their response to histone deacetylase inhibitor [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B125.
Abstract C002: Racial and geographic variation in knowledge of palliative care among American adults
Authors: Jacobs Kayanna , Hong Young Rock , Bian Jiang , Kittelson Sheri , Wilkie Diana J. , Huo Jinhai
Published: September 2020

Introduction Palliative care provides clinical and economic benefits for patients diagnosed with life limiting illness and their family caregivers. The extent to which variation in knowledge of palliative care exits in racial groups and geographic regions within the United States is not known. The aim of the study was to present the up-to-date data on the knowledge penetration of palliative care by racial and geographic regions. Methodology We assessed variations in knowledge of palliative care using the 2018 National Cancer Institute’s Health Information National Trends Survey. We used the Pearson chi-square test and multivariable logistic regression models to assess the association of race and having knowledge of palliative care for each census geographic region. The state-level prevalence of no knowledge of palliative care were plotted in a map. Results The study population included 3194 respondents (weighted sample size: 229,591,005; median age: 58). About 15 % of the study population was Hispanic, 10% non-Hispanic-Black, and 61% non-Hispanic White. About 84% Hispanic respondents, 75% non-Hispanic Blacks and 65% non-Hispanic Whites had no knowledge of palliative care (P <0.001). For Hispanic, the prevalence of no knowledge of palliative care ranged from 48% in East South Central region to 96% in East North Central and West North Central region. For non-Hispanic Blacks, the prevalence of no knowledge of palliative care ranged from 32% in New England region to 97% in West North Central region. For non-Hispanic Whites, the prevalence of no knowledge of palliative care ranged from 44% in New England region to 78% in Mountain region. Both racial group and census geographic regions were statistically significant variables in the multivariable model predicting no knowledge of palliative care. Conclusions In the United States, substantial geographic variations in the knowledge of palliative care exist. The prevalence of responders who had no knowledge of palliative care were greater in Hispanic and non-Hispanic Black than non-Hispanic White groups. This finding represents an opportunity for targeted future education to increase the knowledge gap overall and in patients of non-White decent.

Citation Format: Kayanna Jacobs, Young Rock Hong, Jiang Bian, Sheri Kittelson, Diana J. Wilkie, Jinhai Huo. Racial and geographic variation in knowledge of palliative care among American adults [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C002.
Abstract C097: Navigation needs among African Americans
Authors: Babatunde Oluwole A , Jefferson Melanie , Johnson Jerry C , Hughes-Halbert Chanita
Published: September 2020

Abstract Introduction: Patient navigation is emerging as a strategy for addressing barriers to cancer screening among African Americans; however, navigation should address the specific needs and barriers to obtaining screening. The purpose of this study was to identify navigation needs for cancer screening in a community-based sample of African American men and women. Methods: Participants were enrolled in an observational study of community-based navigation for cancer control. Eligibility criteria were African American men and women aged 50-75 years who resided in the Philadelphia, PA metropolitan area, and had no personal history or symptoms of prostate, breast and colon cancer. The main outcome variable was navigation needs for cancer screening. The exposure variables that were assessed were socioeconomic characteristics, sociocultural factors such perceived risk of developing cancer and future temporal orientation and perceptions of social integration, and history of family members with cancer. Chi square tests and analysis of variance were utilized to assess the associations between potential factors and identified barriers. Results: A total of 268 participants were enrolled in the study and of these, 161 (60%) identified navigation needs for cancer screening: cost/lack of insurance (66, 25%), ignorance/lack of knowledge (73, 27%) and provider issues (22, 8%). The main barrier identified by participants that were younger (<56 years) was cost/lack of insurance (51%) while the main barrier identified by older participants (>56 years) was ignorance/lack of knowledge (47%), [p: 0.04]. Most participants (63%) who had a higher perception of developing breast or prostate cancer identified ignorance/lack of knowledge as barrier to screening while most participants (51%) who had a higher perception of developing colon cancer had cost/lack of insurance as barrier to colon cancer screening, [p: 0.01]. Conclusions: Findings from this study suggest that navigation for cancer screening may need to address lack of knowledge and cost/lack of health insurance. Navigation programs for cancer screening may need to address different needs depending on the age and perceived risk of participants.

Citation Format: Oluwole A Babatunde, Melanie Jefferson, Jerry C Johnson, Chanita Hughes-Halbert. Navigation needs among African Americans [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C097.
Abstract C107: Surveillance mammography and Ffllow-up care in Black and White breast cancer survivors
Authors: Edmonds Megan C , Kim Sunny J , Sheppard Vanessa B
Published: September 2020

Purpose Adherence to surveillance mammography following a breast cancer (BC) diagnosis is a pivotal way to mitigate late stage BC recurrences and ultimately mortality for breast cancer survivors (BCS); yet there are stark racial disparities in adherence to routine follow-up care post-treatment. This study seeks to address disproportionately low adherence rates to breast surveillance guidelines among Black BCS, when compared to White counterparts, by evaluating environmental, social, and psychosocial factors (e.g., attitudes, knowledge) that may influence survivor’s adherence to surveillance mammography. Methods The mixed method designs involve recruiting and screening Black and White BCS concurrently through an epidemiologic survey and online focus groups via social media platforms (e.g., Facebook, Instagram Quora reddit). Data from survey will employ descriptive and bivariate statistics to assess the relationship between environmental, social and psychosocial factors with surveillance mammography and follow-up care. Guided by the Integrated Behavioral Prediction conceptual framework, thematic and linguistic analyses will be conducted for the online focus group text data to find emergent themes and subthemes. Results This study will provide preliminary results highlighting primary factors (e.g., barriers, facilitators) that influence adherence, by race. Our findings will focus on associated factors for women’s adherence to surveillance mammography, to inform survivorship guidelines and clinical practice. Conclusion Knowledge gained from the study will provide clinicians crucial points of communication; identify important modifiable factors needed in survivorship behavioral interventions, and inform strategies for screening messages. Furthermore, understanding factors that support adherence to surveillance mammography among Black BCS will uncover novel approaches to educate and reach this group in efforts to reduce survival disparities.

Citation Format: Megan C Edmonds, Sunny J Kim, Vanessa B Sheppard. Surveillance mammography and Ffllow-up care in Black and White breast cancer survivors [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C107.
Abstract D001: Can small area estimates explain variation in cancer outcomes? 500 cities’ tobacco use estimates and prostate cancer mortality in Philadelphia
Authors: Klassen Ann C , McIntyre Russell , Boamah Maxwell , Keith Scott , Tabb Loni , Ziegler-Johnson Charnita
Published: September 2020

Background: Prostate cancer is the most common cancer in U.S. men, and racial disparities in incidence and mortality persist. Tobacco use has been associated with aggressive histologic grade and mortality; however, population-based cancer registries have limited data on lifetime tobacco use or SHS exposure. Community-level small-area estimates calculated from individual-level survey data offer a useful tool for understanding neighborhood effects, and estimating individual behaviors when direct observation is not feasible. Methods: This project used data on all 2005-2014 incident prostate cancer cases in Philadelphia, a city with high burden from both tobacco use and poverty. Using multi-level models, the odds of death from prostate cancer were estimated in relation to individual case characteristics (age, race, year of diagnosis, and tumor histologic grade) and Census tract-level estimates of tobacco use, using CDC’s 500 Cities small area estimates. Mediation analyses were used to examine whether tobacco use plays a role in the relationship between race and both aggressive histologic grade and prostate cancer related mortality. Results: From 2005-2014, 6% of the 10621 cases died from prostate cancer. Cases residing in Census tracts with higher estimated proportion of adults who smoke were more likely to have aggressive grade tumors, and more likely to die from their cancer. Analyses revealed that aggressive grade partially mediated the relationship between tobacco use and cancer death, and that tobacco use partially mediated the relationship between black race and cancer death. Conclusions: Findings support the utility of small area estimates for investigating area-level influences in exploratory studies.

Citation Format: Ann C Klassen, Russell McIntyre, Maxwell Boamah, Scott Keith, Loni Tabb, Charnita Ziegler-Johnson. Can small area estimates explain variation in cancer outcomes? 500 cities’ tobacco use estimates and prostate cancer mortality in Philadelphia [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D001.
Abstract D013: EHE Foundation
Authors: Deoras-Sutliff Medha
Published: September 2020

The EHE Foundation leads the global fight against this rare vascular cancer, considered a sarcoma sub-type. Our mission is to seek treatments and a cure for Epithelioid Hemangioendothelioma (EHE) by increasing awareness, pursuing scientific research, advocating for and supporting EHE patients, and bridging information between researchers, providers and patients. Developing and funding a comprehensive and scientifically rational research strategy is a priority. Connecting to partners and constituents in the sarcoma community but also world-wide through sister charities in Canada, UK and Australia helps streamline and focus research and patient support efforts. Alone we are Rare, Together we are Stronger.

Citation Format: Medha Deoras-Sutliff. EHE Foundation [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D013.
Abstract D014: Assessing an intervention to increase cervical cancer knowledge and HPV vaccination knowledge among predominantly African American communities in South Carolina
Authors: Ford Marvella E , Cannady Kimberly , Hazelton NiAsia , Knight Kendrea D , Lawton Claudia , Malek Angela M , Salley Judith D
Published: September 2020

BACKGROUND: Human papilloma virus (HPV) is linked to cervical cancer incidence. The HPV vaccine has been shown to significantly reduce the risk of HPV infection and subsequent cervical cancer diagnosis. Unfortunately, African Americans (AA) show lower uptake of the HPV vaccine than other groups. Underuse of the HPV vaccine has been linked to lack of knowledge of its effectiveness in preventing cervical cancer. OBJECTIVES: The purpose of this study was to evaluate an educational intervention to improve cervical cancer knowledge and HPV vaccine knowledge among predominantly AA communities in South Carolina (SC). METHODS: The study was conducted in a convenience sample of residents of five SC counties with high racial disparities in cervical cancer mortality rates that were recruited by community partners. The intervention consisted of a 4.5-hour educational session with 8 different components including a 30-minute cervical cancer/HPV vaccination knowledge component. Pre-and post- intervention surveys were administered. MEASURES: A 7-item investigator-developed instrument was used to evaluate pre-/post-intervention changes in cervical cancer knowledge and HPV vaccination knowledge. The items were based on the investigators’ review of the contemporary literature on the topics of cervical cancer, HPV infection, and the HPV vaccine. RESULTS: The first sample consisted of 64 participants from last year and this year participants consisted of 28 which make 92 in all (99% AA). Most of the participants who reported age were 50+ years. Among those who reported gender, 90% were female. Among those who reported income, 80% had an annual household income >$40,000. Seventy-two percent of the participants who reported their educational level had received at least some college training. Conclusions: Providing cervical cancer and HPV vaccination information leads to increasing knowledge related to cervical cancer and the HPV vaccine. In the future study, the investigators will evaluate changes in the pre-/post-intervention. HPV vaccination uptake rates in the five counties where the intervention was conducted.

Citation Format: Marvella E Ford, Kimberly Cannady, NiAsia Hazelton, Kendrea D Knight, Claudia Lawton, Angela M Malek, Judith D Salley. Assessing an intervention to increase cervical cancer knowledge and HPV vaccination knowledge among predominantly African American communities in South Carolina [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D014.
Abstract D018: Dietary and cultural practices of minorities in New York City as an indicator of colorectal cancer screening behavior and screening intent
Authors: Johnson Cicely K.
Published: September 2020

There are significant racial and gender disparities in health behaviors and health outcomes in the United States, and these differences are vast and not well understood. As colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, and African Americans have the highest colorectal cancer incidence and mortality rates of all racial groups in the U.S., it is essential to ascertain the interplay between individual health behaviors that may be unique racial patterns, and health outcomes. This research study is a pilot study that is a part of a larger study with existing preliminary data on the intersection between diet and colorectal cancer. This pilot study examines dietary habits and practices of individuals identifying as Black as a predictor for colorectal cancer screening. This study will assess the relationship between dietary habits and screening behavior and intent. This study will evaluate the correlation between individuals with a higher intake of healthy options and their intent to screen for colorectal cancer within a year. The novelty of this study is rooted in its utilization of a study sample that includes participants who are not currently age eligible for screening according to the new recommended guidelines, but will be age eligible within the next five years, utilization of a novel variable such as dietary habits to correlate with screening behavior and intent, extracting differences by gender, and extracting differences by ethnicity. Future work of this study will be concerned with gathering qualitative data around the interrelationship of culture and diet as it pertains to screening behavior and intent, and the multiple variations of that interrelationship by ethnicity. Results of this significant study can provide health educators, providers and policy makers information that is critically necessary in an effort to create culturally relevant health promotion materials within the diverse Black community.

Citation Format: Cicely K. Johnson. Dietary and cultural practices of minorities in New York City as an indicator of colorectal cancer screening behavior and screening intent [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D018.
Abstract D086: Assessing patient-level knowledge of precision medicine in a community health center setting
Authors: Aldrich Melinda C , Blot William J
Published: September 2020

Factors influencing cancer treatment decisions require comprehension of genetic tests, risk stratification, and treatment options. This comprehension in turn requires understanding of numeracy, genetic literacy, health literacy, and medical trust, all important for acceptance and implementation of precision medicine. Using a mixed methods approach, we sought to identify patient-level factors influencing the understanding of cancer risk and precision medicine among community health center patients. At a community health center in Nashville, Tennessee we enrolled 26 English-speaking patients between the ages of 40-79 years who were either a cancer patient (n=4), had a family member with cancer (n=20), and/or were previously a caregiver for a cancer patient (n=15). The participants enrolled in one of four focus groups, and also completed surveys to assess patient-level understanding of precision medicine, numeracy, and health literacy. We used a three-item health literacy screening questionnaire and the Subjective Numeracy Scale to assess health literacy and numeracy, respectively. Participants were median age 60, 89% African American and 77% female, with 35% having a high school degree or less and 35% a household income of ≤$15,000. While health literacy was generally high (≤15% reported low confidence in filling out medical forms, understanding medical information, or needing help to read the information), 42% felt that genes or genetics had little impact on health and most reported little familiarity with precision medicine (69%), pharmacogenetics (77%), biomarkers (81%) or biobanks (81%). The majority of participants reported that trust in their providers was extremely or very important when receiving genetic tests (77%) and over 60% felt receiving genetic test results was extremely important. Numeracy levels were moderate, with nearly half reporting some discomfort working with fractions and 38% finding numerical information only occasionally useful. The findings suggest that many patients lack familiarity with precision medicine concepts relevant for understanding cancer treatment decisions. Future efforts in digital technologies may be able to help bridge the gap in patient understanding and allow medically underserved populations to have equitable opportunities for precision medicine.

Citation Format: Melinda C Aldrich, William J Blot. Assessing patient-level knowledge of precision medicine in a community health center setting [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D086.
Abstract D114: VIitamin D signaling of immune-related genes in diverse prostate cancer cancer cell lines
Authors: Bathina Madhavi , Woods-Burnham Leanne , Walker Mya S , Kimbro K Sean , Kittles Rick A
Published: September 2020

BACKGROUND: African American (AA) men are disproportionately affected by both prostate cancer (PCa) and vitamin D deficiency compared with European American (EA) men. Vitamin D deficiency is linked to increased PCa aggressiveness and mortality. Inflammation also plays an important role in PCa pathogenesis and progression, and expression of immune-related in genes in PCa tissues differs significantly between AAs and EAs. While evidence linking vitamin D and immune response to PCa remains scarce, previous studies demonstrated that vitamin D has anti-inflammatory effects in prostate tissue and mediates immune-related gene expression. Therefore, we hypothesize that vitamin D deficiency in AA men may alter the expression of immune-related genes associated with prostatic inflammation and PCa progression. METHODS: This study examined the effects of vitamin Don the expression of vitamin D- and immune-related genes. Weexposed a racially diverse panel of PCa cell lines—MDA-PCa-2b (AA), RC77T/E (AA), PC3 (EA), 22Rv1 (EA), and DU145 (EA)—to various concentrations (2.5 nM, 10 nM, 50 nM) of 25-hydroxyvitamin D (25(OH)D) and 1,25 dihydroxyvitamin D (1,25(OH)2D) for 24 hours, and quantified transcript levels and protein expression of VDR, RXRa, RXRb, LRP2, CYP27B1, GDF15, GFRAL, TNFa, IL6, IL8, and IGFBP3 with qPCR and immunoblotting. RESULTS:All cell lines expressed basal levels of VDR, RXRa, and RXRbconfirming the function of vitamin D signaling within PCa cells. Of the downstream immune-related genes tested, we observed a trend demonstrating that vitamin D treatment induced the greatest upregulation in either transcript and/or protein levels among the AA PCa cell lines RC77T/E and/or MDA-PCa-2b. In particular, LRP2, GDF15, TNFa, IL6, IL8, and IGFBP3 significantly increased in AA PCa cell lines exposed to either 25(OH)D or 1,25(OH)2D. CONCLUSIONS: These findings provide insight into a potential differential regulation of immune-related pathways by vitamin D in AA men compared to EA men with PCa. Further studies are warranted to better define the immune profile in prostatic tissue in response to vitamin D deficiency in AA men, and the downstream inflammatory effects on the microenvironment and tumor aggressiveness.

Citation Format: Madhavi Bathina, Leanne Woods-Burnham, Mya S Walker, K Sean Kimbro, Rick A Kittles. VIitamin D signaling of immune-related genes in diverse prostate cancer cancer cell lines [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D114.
Abstract D132: The association between Insurance and lung cancer survival: The relative contributions of sociodemographic, tumor, treatment, and neighborhood factors
Authors: Liu Ying , Lian Min , Colditz Graham
Published: September 2020

Health insurance is associated with lung cancer treatment and survival. It remains unclear to what extent insurance-associated survival disparities are attributed to prognostic factors of lung cancer. Using the Surveillance, Epidemiology, and End Results dataset, we identified 127,784 patients (age<65) diagnosed with lung cancer between 2007 and 2016. Cox proportional hazards regression was used to compute hazard ratios (HRs) of lung cancer-specific mortality. Relative contributions of prognostic factors to survival disparities were quantified by percent changes in HRs with sequential adjustment for marital status, socioeconomic deprivation, rurality, cancer stage, size, histology, surgery, radiation therapy, and chemotherapy. Difference in differences analysis was performed to examine the associations between Medicaid expansion and changes in proportions of no insurance and early-stage diagnosis, and 2-year survival rates. Compared with privately insured counterparts, the risk of cancer-specific mortality was significantly increased in uninsured men (HR=1.51, 95% CI 1.47-1.56; 5-year absolute risk difference (ARD)=12.5%, 95% CI 11.6%-13.3%) in uninsured men, Medicaid men (HR=1.36, 95% CI 1.33-1.39; 5-year ARD=9.6%, 95% CI 9.0%-10.3%), uninsured women (HR=1.66, 95% CI 1.59-1.72; 5-year ARD=17.0%, 95% CI 15.8%-18.2%), and Medicaid women (HR=1.41, 95% CI 1.38-1.45; 5-year ARD=12.0%, 95% CI 11.2%-12.9%) after adjustment for age, race, and registries. Further adjustment for the aforementioned factors explained 63.7%-70.6% of survival disparities. Medicaid expansion was associated with a greater reduction in uninsured rates (2.0 percentage point (ppt), p<.0001), and a greater increase in the proportion of early-stage diagnosis (2.1 ppt, p<0.01) and 2-year survival (1.3 ppt, p=0.04) in men only, after adjustment for covariates. The study provided evidence for worse survival in uninsured and Medicaid lung cancer patients compared with privately insured counterparts, more than half of which were attributable to sociodemographic, tumor, treatment, and neighborhood factors. Medicaid expansion was associated with shift towards early-stage diagnosis and improvements in short-term survival in men with lung cancer.

Citation Format: Ying Liu, Min Lian, Graham Colditz. The association between Insurance and lung cancer survival: The relative contributions of sociodemographic, tumor, treatment, and neighborhood factors [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D132.
Abstract IA15: Breast cancer screening opportunities in sub-Saharan Africa
Authors: Chong Alice
Published: September 2020

Breast cancer, the most common cancer in women worldwide, is largely curable in high-income countries when detected early. In the low- and middle-income countries (LMICs), including those in sub-Saharan Africa, breast cancer usually presents as a late-stage disease that is associated with high mortality rates. Using specific country examples, the presentation covers tailored strategies for breast cancer screening and early detection in low-resource settings, which should be undertaken only after diagnostic and treatment infrastructure is assured.

Citation Format: Alice Chong. Breast cancer screening opportunities in sub-Saharan Africa [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA15.
Abstract A03: Isolation, characterization, and expansion of circulating tumor cells in head and neck cancers
Authors: Kulasinghe Arutha , Kapeleris Joanna , Kenny Liz , Warkiani Majid , Vela Ian , Thiery Jean Paul , O’Byrne Ken , Punyadeera Chamindie
Published: September 2020

Metastasis in head and neck cancer (HNC) patients is reflected by measurable levels of circulating tumor cells (CTCs) in the blood of patients. CTCs represent cancer cells from the primary and metastatic sites, thereby providing a comprehensive representation of the tumor burden of an individual patient. Recent advancements have shown that PD-1/PD-L1 immune checkpoint therapies have durable responses in HNC. Our study was designed to use multiple CTC enrichment platforms for the capture of CTCs and novel culture formulations for the ex vivo expansion of CTCs. n=300 head and neck cancer patients were recruited to investigate the prognostic role of CTCs. We evaluated multiple CTC isolation technologies (CellSearch, filtration, CD45 depletion, inertial microfluidics) using matched patient samples, which showed that epitope-independent CTC isolation captured a greater proportion of CTCs. Molecular alterations present in the primary tissue were confirmed in the CTCs by 3D-DNA FISH (EGFR-amplification). The presence of CTC clusters was associated with the development of distant metastatic disease (P=0.0313). HNC CTC-positive patients had shorter progression-free survival (PFS) (Hazard ratio [HR]: 4.946; 95% confidence interval [CI]:1.571-15.57; P=0.0063) and PD-L1-positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011-26.33; P=0.0485). In a proof-of-principle study, we were able to demonstrate for the first time short-term patient-derived CTC cultures outside the patient’s body from 7/18 HNC samples (4/7 HPV-positive). Recently, we have preliminary data that suggest that PD-L1 is frequently expressed on CTCs in HNC and an immunoscore may be able to identify patients likely to benefit from immunotherapy—a current unmet clinical need. Expanding CTCs outside the patient’s body allows for the recapitulation of the molecular diversity present within the tumor, understanding of the disease progression, and testing of therapies.

Citation Format: Arutha Kulasinghe, Joanna Kapeleris, Liz Kenny, Majid Warkiani, Ian Vela, Jean Paul Thiery, Ken O’Byrne, Chamindie Punyadeera. Isolation, characterization, and expansion of circulating tumor cells in head and neck cancers [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A03.
Abstract A14: The p53R172H gain-of-function mutation promotes resistance to oral cancer immunoprevention
Authors: Wang Jin , Hu Yuan , Gonzalez Cassandra , Tang Lin , Wang Bingbing , El-Naggar Adel , Myers Jeffrey , Caulin Carlos
Published: September 2020

Oral squamous cell carcinomas (OSCC) tend to develop from oral premalignant lesions (OPLs) through the accumulation of genetic alterations. Therefore, effective prevention strategies designed to block the malignant progression of OPLs are expected to contain the development of aggressive carcinomas. Our previous studies showed that immune checkpoint blockade can prevent the progression of OPLs to OSCC, in a mouse model for oral carcinogenesis. However, a subset of the lesions continued to progress even after treatment with anti-PD1 antibodies. Mutations that accumulate in the epithelial cells of the oral lesions may shape the immune microenvironment of the oral lesions and impact the response to immunotherapies. The p53 gene (TP53) is the most frequently mutated gene in OSCCs, as over 80% of the OSCCs contain p53 mutations. Most p53 mutations found in human cancers are missense mutations that encode mutant forms of p53, some of which are associated with poor clinical outcomes and can transform cells as a result of their gain-of-function (GOF) activities. To assess the role of p53 mutations in the response to anti-PD-1 immunoprevention, we generated mouse models in which oral tumors were induced by the carcinogen 4NQO in genetically engineered mice in which the p53 GOF mutation p53R172H or deletion of p53, a loss-of-function (LOF) mutation, were activated in oral epithelial cells. Therefore, the OPLs that developed in these mice differed in their p53 status. We found that the oral lesions that developed in these mice showed a gradual increase in T-cell infiltration during oral cancer progression, the recruitment of immunosuppressive regulatory T-cells (Tregs), and induction of PD-1/PD-L1 immune checkpoint proteins. Remarkably, while PD-1 blockade prevented the development of SCCs in mice with wild-type p53 or p53 deletion, the GOF mutant p53R172H abrogated the immunopreventive effects of anti-PD-1 antibodies, associated with depletion of exhausted CD8 cells in the microenvironment of the p53R172H tumors. Overall, these findings indicate that mutant p53R172H promotes the development of an immune microenvironment that prevents the efficacy of PD-1 inhibitors. These studies suggest that p53 profiling may help to predict the response to oral cancer immunoprevention, and patients with OPLs containing wild-type p53 or p53 LOF mutations may benefit from the immunopreventive effects of anti-PD1 antibodies.

Citation Format: Jin Wang, Yuan Hu, Cassandra Gonzalez, Lin Tang, Bingbing Wang, Adel El-Naggar, Jeffrey Myers, Carlos Caulin. The p53R172H gain-of-function mutation promotes resistance to oral cancer immunoprevention [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A14.
Abstract A20: Dysgeusia may play a role in negatively affecting mood and anxiety in post-radiation head and neck patients
Authors: Arnell Thomas , Self Quinn , Li Sharon , Nelson Carl
Published: September 2020

Introduction: Anxiety and depression are well-documented comorbid conditions that many patients with head and neck cancer experience. Furthermore, radiation therapy for many head and neck cancers is associated with significant morbidity. Dysgeusia, in particular, is almost universally experienced with total taste loss occurring in up to 73% of individuals radiated for head and neck cancers. Prior studies have demonstrated a significant correlation between decreased quality of life and dysgeusia. In this retrospective study, we wish to further characterize the association between taste disturbance and patient-reported anxiety and mood. With better understanding of this relationship, we may be able to effectively intervene in improving the quality of life for head and neck patients.

Methods: Forty-nine patients at The University of Vermont Medical Center who completed radiation therapy for head and neck cancer completed the University of Washington Quality of Life (QOL) Questionnaire at scheduled follow-up visits. Surveys were reviewed retrospectively for QOL measures, specifically patient-reported anxiety, mood, and taste.

Results: Taste scores were the lowest at follow-up weeks 0-3 and more than tripled by the last follow-up, at 48 weeks (p>0.0001). The trend in taste improvement was most rapid during the first few weeks after radiation, but leveled off after 12 weeks. Mood and anxiety similarly improved across weeks after radiation when compared against taste.

Conclusion: Our data suggest a correlation between taste disturbance, mood, and anxiety in patients after head and neck radiation. This suggests that targeting treatments to improve patients’ sense of taste post-radiation may improve their psychiatric well-being.

Citation Format: Thomas Arnell, Quinn Self, Sharon Li, Carl Nelson. Dysgeusia may play a role in negatively affecting mood and anxiety in post-radiation head and neck patients [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A20.
Abstract B10: Manipulating translesion synthesis proteins MAGE-A4 and RAD18 in a murine model of oral cancer
Authors: Wagner Bethany L. , Guo Jason , Gao Yanzhe , Vaziri Cyrus , Williams Scott E.
Published: September 2020

Head and neck squamous cell carcinomas (HNSCCs) account for 6% of cancers worldwide. Because of their link to carcinogens such as alcohol and tobacco, HNSCCs are characterized by a high mutational burden and genome instability. Cancer recurrence due to chemoresistance, or a tolerance of chemotherapy-induced mutations, is the major cause of mortality in HNSCCs. DNA damage response pathways, such as translesion synthesis (TLS), are activated in response to genotoxic stress, including from conventional chemotherapy. The TLS pathway facilitates repair of certain types of mutations and thus is important for DNA damage tolerance. However, TLS polymerases are error-prone and therefore, paradoxically, may promote genome instability. In this way, elevated or “pathologic” TLS in the context of a cancer cell may be a “double-edged sword,” conferring damage tolerance but at the expense of introducing additional mutations that could fuel tumor growth. We have previously shown that melanoma antigen A4 (MAGE-A4) recruits the E3 ubiquitin ligase Rad18 to stalled replication forks where it monoubiquitinates PCNA to recruit TLS polymerases to bypass the lesion. In HNSCC, MAGE-A4 overexpression correlates with both increased mutational burden and worse prognosis. We hypothesize that aberrant high MAGE-A4 expression tolerizes cancer cells to excessive mutations, making them invulnerable to the DNA-damaging effects of traditional chemotherapies. In order to gain a better understanding of the consequences of MAGE-A4 overexpression and TLS activation in oral tumors in vivo, we created a genetically engineered mouse model that expresses MAGE-A4 under the control of an epithelial-specific Cre driver. When treated with the potent mutagen 4NQO in their drinking water, both transgenic and control mice developed oral tumors. The collected squamous cell carcinomas were analyzed using whole-exome sequencing and immunofluorescence to examine whether MAGE-A4+ tumors gained more mutations and were more invasive than MAGE-A4- or RAD18 KO tumors. Together, these data provide a greater understanding of MAGE-A4 and RAD18 biology and TLS in oral cancers.

Citation Format: Bethany L. Wagner, Jason Guo, Yanzhe Gao, Cyrus Vaziri, Scott E. Williams. Manipulating translesion synthesis proteins MAGE-A4 and RAD18 in a murine model of oral cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B10.