Louisiana Cancer Research Articles

Impact of rural location on receipt of standard of care treatment and survival for locally advanced bladder cancer in Louisiana.

We aim to determine the effect of region of residence (urban vs. rural) on the odds of receiving standard of care treatment for locally advanced BCa in Louisiana and its impact on survival outcomes. Using the Louisiana Tumor Registry, we identified American Joint Committee on Cancer (AJCC) stage II or III, BCa diagnoses in Louisiana residents between 2010 and 2020. Treatment received was classified as standard or non-standard of care according to American Urological Association (AUA) guidelines and location of residence was determined using Rural Urban Commuting Area-Tract-level 2010 (RUCA). Multivariable logistic regression analyses and multivariate cox proportional hazard analyses were performed. Of 983 eligible patients, 85.6% (841/983) lived in urban areas. Overall, only 37.5% received standard-of-care (SOC) for the definitive management of locally advanced bladder cancer. Individuals living in rural areas (OR 0.53, 95% CI: 0.31-0.91, p = 0.02) were less likely to receive standard of care treatment. Both rural residence and receipt of non-standard of care therapy were associated with an increased risk of bladder cancer-specific (adj HR 1.53, 95% CI: 1.09-2.14, p = 0.01 and adj HR: 1.85, 95% CI: 1.43-2.39, <0.0001) and overall mortality (adj HR: 1.28, 95% CI: 1.01-1.61, p = 0.04 and adj HR: 1.73 95% CI: 1.44-2.07, p < 0.0001). Most patients with locally advanced bladder cancer in Louisiana do not receive SOC therapy. Individuals living in rural locations are more likely to receive non-standard of care therapy than individuals in urban areas. Nonstandard of care treatment and rural residence are both associated with worse survival outcomes for Louisiana residents with locally advanced bladder cancer.

Abstract PO2-25-11: Incidence of Breast Cancer in Louisiana Compared to the United States

Abstract Aside from skin cancer, breast cancer is the most common cancer in American women. More specifically, one in eight women will develop breast cancer during their lifetime. Breast cancer is classified into subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). ER+/PR+/HER2- tumors are the most common form of breast cancer and are typically associated with risk factors including older age, nulliparity, obesity following menopause, alcohol and tobacco use, sedentary lifestyle, and hormone therapy. ER-/PR-/HER2+ tumors comprise approximately 15-20% of breast cancers and are caused by overexpression of the HER2 gene. These tumors have similar risk factors to ER+/PR+/HER2- tumors, except for age. Women with HER2+ breast cancer are likely to be younger compared to ER+PR+/HER2-. Tumors lacking hormone receptors are classified as ER-/PR-/HER2-, otherwise known as triple-negative breast cancer (TNBC). TNBC represents 10%-20% of breast cancers and carries a poorer prognosis, shorter survival, and unresponsiveness to hormone therapy compared to other forms of breast cancer. TNBC has been associated with African American race, socioeconomically deprived population, younger age at diagnosis (most frequently in women ages 40-50), more advanced disease stage, higher grade, high mitotic indices, family history of breast cancer and BRCA1 mutations. The primary aim of this study is to compare incidence of ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2- (TNBC) in Louisiana to the national population. The Louisiana Tumor Registry (LTR) was utilized to obtain state and national level data. The LTR is a participant of the National Cancer Institute’s Surveillance, Epidemiology and End Results Program, and the Centers for Disease Control and Prevention’s National Program of Cancer Registries. Our study evaluated women in Louisiana diagnosed with ER+/PR+/HER2-, ER-/PR-/HER2+, and ER-/PR-/HER2- from 2010-2019. The populations were subdivided by age at time of diagnosis. Data was subdivided into ages 0-49, and &amp;gt;50. Rates were calculated per 100,00 and age-adjusted to the 2000 United States Standard Population (19 age groups - Census P25-1130). A p-value of &amp;lt; 0.05 indicates a significantly different rate in Louisiana comparative to the United States (SEER). Our results are as follows. Unexpectedly, Louisiana has a significantly lower rate of ER+/PR+/HER2- cancer in women ages 0-49 and ages &amp;gt;50 compared to the United States. Based on epidemiological risk factors, Louisiana should have a much higher rate of ER+/PR+/HER2- comparative to the United States population. Louisiana has a significantly higher rate of ER-/PR-/HER2+ cancer in women ages &amp;gt;50 and ER-/PR-/HER2- (TNBC) in women ages 0-49 and ages &amp;gt;50 compared to the United States. These findings are discordant with traditional epidemiologic studies regarding breast cancer and require further investigation. Breast Cancer Incidence Rates1 by Age from 2010-2019 in Louisiana and the United States Table 1: Breast Cancer Incidence Rates in women ages 0-49 and ages &amp;gt;50 from 2010-2019 in Louisiana Compared to the United States. Citation Format: Avery Daily, Julie Cupp, Krystle Trosclair. Incidence of Breast Cancer in Louisiana Compared to the United States [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-25-11.

Abstract 4822: Disparities in receiving non-surgical therapy impact outcomes in non-metastatic gastric cancer in Louisiana

Abstract Background: Given the history of evolving medical therapies and advancements in cancer treatments over the last decades, resectable gastric cancer has presented multiple strategies for care. Previous literature indicates historically decreased use of multimodal therapies in minority populations. This study aims to evaluate Louisiana patient populations for rates of definitive treatment, inequities in access to care, and evaluating its impact on the outcomes of minorities and underserved population. Methods: Patients with non-metastatic primary invasive gastric cancer, with T2-4 or any T status with positive lymph nodes, were identified in the Louisiana Tumor Registry using ICD-O codes and AJCC staging system. Receipt of non-surgical therapy was modeled using logistic regression. Overall survival (OS) was modeled using a Cox proportional hazards model. Results: The study included 561 patients, of which 37.6% (n=211) did not receive surgical treatment and 16.2% (n=91) did not receive non-surgical therapy. A subset of the cohort received no definitive treatment, (6.8%, n=38). In a demographic only multivariable model, adjusting for age, sex, and race, age 70 and over [OR (95%CI) =0.18 (0.08-0.42), p&amp;lt;0.001] and female sex [OR (95%CI) =0.48 (0.28-0.85), p=0.011] was associated with decreased rates of non-surgical therapy. Black [OR (95%CI) = 0.54 (0.31-0.93), p=0.027] and Hispanic [OR (95%CI) = 0.38 (0.13-1.08), p=0.070] race was associated with decreased receipt of non-surgical therapies. However, after adjusting for domestic partner, insurance status, rurality, area poverty, and surgery status, racial disparities were no longer significant compared to whites: Black [OR (95% CI) = 0.59 (0.33-1.06), p=0.075]; Hispanic [OR (95% CI) = 0.52 (0.17-1.66), p=0.272]. In multivariable analyses, receipt of surgery [HR (95% CI) = 0.3 (0.23 - 0.38), p&amp;lt;0.001) and any non-surgical therapy [HR (95% CI) = 0.43 (0.31 - 0.60), p&amp;lt;0.001) were associated with increased overall survival. Conclusion: A significant number of patients did not receive all modalities of the multidisciplinary treatment that is recommended for patients with non-metastatic gastric adenocarcinoma. Black patients and females are less likely to receive non-surgical modalities for gastric cancer in Louisiana, which is, at least, partially driven by socioeconomic determinants. Identifying patients with these risk factors is a crucial step in allocating resources to increase access the care and improve outcomes. Citation Format: Conner D. Hartupee, Kyla Maupin, Denise M. Danos, Omeed Moaven. Disparities in receiving non-surgical therapy impact outcomes in non-metastatic gastric cancer in Louisiana [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4822.

Comparative impact of the affordable care act on breast cancer outcomes among women in two US states.

Since the implementation of the Patient Protection and Affordable Care Act (ACA) and Medicaid expansion, states that adopted the policy have seen reduced uninsured rates. However, it is unclear whether increased healthcare access, particularly for minority and socioeconomically disadvantaged groups, has translated into measurable improvements in health outcomes. Our study aims to evaluate the impact of the ACA and Medicaid expansion on breast cancer outcomes in Louisiana, which has implemented the policy, compared to Georgia, which has not, as of 2024. We conducted a retrospective study using SEER registry data from January 2011 to December 2021, including women aged 18-64 diagnosed with breast cancer. The impact of the ACA and Medicaid expansion on cancer-specific survival (CSS), overall survival (OS), and stage at presentation was evaluated. The cohort was divided into pre-ACA (2011-2015) and post-ACA (2017-2021) periods, with a one-year washout (2016). A difference-in-difference (DID) approach compared outcomes between Louisiana and Georgia. The study analyzed 62,381 women with breast cancer, with 32,220 cases in the pre-ACA period (51.7%) and 30,161 in the post-ACA period (48.3%). In Georgia, 43,279 women were included (52.3% pre-ACA vs. 47.7% post-ACA), while Louisiana had 19,102 women (50.1% pre-ACA vs. 49.9% post-ACA). Medicaid expansion in Louisiana was associated with a 0.26 percentage point reduction in overall deaths (95% CI: -10.9 to 10.4) and a 5.97 percentage point reduction in cancer-specific mortality (95% CI: -26.1 to 14.2). There was also no significant difference in disease stage at presentation compared to Georgia. This study found no significant differences in overall mortality, cancer-specific mortality, or disease stage at presentation among women with breast cancer in Louisiana, which implemented Medicaid expansion in 2016, compared to Georgia, which has not expanded Medicaid.

Disparities in surgical management and outcomes of patients with primary liver cancer in Louisiana

Disparities in surgical management and outcomes of patients with primary liver cancer in Louisiana

Association of Obesity and Diabetes With the Incidence of Breast Cancer in Louisiana

Breast cancer is a heterogeneous disease, consisting of multiple molecular subtypes. Obesity has been associated with an increased risk for postmenopausal breast cancer, but few studies have examined breast cancer subtypes separately. Obesity is often complicated by type 2 diabetes, but the possible association of diabetes with specific breast cancer subtypes remains poorly understood. In this retrospective case-control study, Louisiana Tumor Registry records of primary invasive breast cancer diagnosed in 2010-2015 were linked to electronic health records in the Louisiana Public Health Institute's Research Action for Health Network. Controls were selected from Research Action for Health Network and matched to cases by age and race. Conditional logistic regression was used to identify metabolic risk factors. Data analysis was conducted in 2020‒2021. There was a significant association between diabetes and breast cancer for Luminal A, Triple-Negative Breast Cancer, and human epidermal growth factor 2‒positive subtypes. In multiple logistic regression, including both obesity status and diabetes as independent risk factors, Luminal A breast cancer was also associated with overweight status. Diabetes was associated with increased risk for Luminal A and Triple-Negative Breast Cancer in subgroup analyses, including women aged ≥50 years, Black women, and White women. Although research has identified obesity and diabetes as risk factors for breast cancer, these results underscore that comorbid risk is complex and may differ by molecular subtype. There was a significant association between diabetes and the incidence of Luminal A, Triple-Negative Breast Cancer, and human epidermal growth factor 2‒positive breast cancer in Louisiana.

Abstract 997: γ-Tocotrienol inhibition of metastatic phenotypic behavior is associated with a decrease in galectin-3 expression and distribution in the highly malignant mouse +SA &amp; TS/A mammary tumor cells

Abstract γ-Tocotrienol is a rare natural isoform of vitamin E that displays potent apoptotic and anti-metastatic activity against breast cancer. Galectin-3 is a protein that plays an important role in metastasis by binding to glycoconjugates on receptors and extracellular matrix proteins. Studies were conducted to investigate the effects of γ-tocotrienol on galectin-3 expression and morphology in highly malignant +SA, TS/A MDA-MB-231 tumor cells. Computer-aided molecular modeling studies compared anticancer agents, salirasib and γ-tocotrienol, with the active site of galectin-3 and β-lactose (a known ligand). Results showed that γ-tocotrienol displays similar galectin-3 amino acid interactions as β-lactose and salirasib. Protein docking show that salirasib (active binding -2.8) and γ- tocotrienol (active binding -2.87) had similar binding scores and binding moieties. Immunocytochemical fluorescent staining show that γ-tocotrienol treatment disrupted galectin-3 expression and distribution, and a corresponding reduction in +SA cellular migration similar to that induced by β-lactose. Western blot analysis shows that γ-tocotrienol treatment induces a downregulation of galectin-3 expression. Immunocytochemistry studies shows that galectin-3 is highly expressed in +SA and TS/A cells, and γ-tocotrienol greatly reduced galectin-3 expression and distribution Furthermore, galectin-3 was found to form extracellular structures on the outer membrane of +SA, TS/A, and MDA-MB-231 cells, and γ-tocotrienol greatly attenuated galectin-3 and fibronectin distribution. γ-Tocotrienol treatment decreased f-actin stress fibers distribution in all cell lines. Furthermore, treatment with 1.5 μM histamine significantly stimulated +SA mammary tumor cell migration, whereas combination treatment with 5 μM γ-tocotrienol completely blocked histamine-induced +SA cell migration. In TS/A cells, 6-15 μM tocotrienol induced a dose-responsive increase in doxorubicin staining inside the nucleus. In MDA-MB-231 cells, syncytial cells were associated with galectin-3 expression and this was suppressed by 5-15 μM γ-tocotrienol. In summary, these results demonstrate that γ-tocotrienol treatment inhibits extracellular galectin-3 expression and disrupts galectin-3 carbohydrate binding and activation of +SA, TS/A and MDA-MB-231 breast cancer cells. These findings also suggest that γ-tocotrienol may provide significant benefits in the prevention and/or treatment of metastatic breast cancer. This study was supported in part by funding from the Louisiana Cancer Foundation. Citation Format: Paul W. Sylvester, Jessie J. Grazier. γ-Tocotrienol inhibition of metastatic phenotypic behavior is associated with a decrease in galectin-3 expression and distribution in the highly malignant mouse +SA &amp; TS/A mammary tumor cells [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 997.

Abstract 967: γ-Tocotrienol inhibition of androgen receptor (AR) expression and activation in triple negative breast cancer (TNBC) MBA-MB-231 and MDA-MB-453 cells is associated with a reduction in epithelial-to-mesenchymal transition (EMT)

Abstract Triple-negative breast cancers (TNBC) are a subset of breast cancer that is highly aggressive and has a poor prognosis. The TNBC subtype has no effective molecular targeted therapies. Gene expression studies have identified a subset of TNBC that is enriched with androgen receptors (AR) and androgen receptor signaling. AR levels are most abundant in the luminal AR (LAR) molecular subtype of TNBC, but other non-LAR molecular TNBC subtypes also display high levels of AR expression and activity. Interference with androgen signaling in TNBC with AR-inhibiting drugs have shown a reduction in epithelial-to-mesenchymal transition (EMT), which is a process by which epithelial cells lose their cell polarity and cell-cell adhesion and gain migratory and invasive properties to become mesenchymal-like stem cells. Approximately one-third of TNBC expressed AR, and evaluation of AR-positive TNBC primary tumors shows nuclear localization of AR, an indication of transcriptionally active receptors. Previous studies have shown that AR inhibition or AR knockdown significantly reduces migration and invasion and EMT in different TNBC cell lines. γ-Tocotrienol is a member of the vitamin E family of compounds that displays potent anticancer effects and have little or no effect on normal cell viability. Studies show that treatment with 0-7 µM γ-tocotrienol reduced AR levels, proliferation, migration and invasion in a dose-responsive manner in TNBC MDA-MB-231 and MDA MB-453 cell lines. Results also show that treatment with 5 µM (MDA-MB-231) and 7 µM (MDA-MB-453) γ-tocotrienol induced a reversal in EMT cell biomarkers, as well as reversal in EMT morphological and behavioral characteristics in these TNBC cell lines. Western blot analysis show that similar treatment with γ-tocotrienol significantly decreased DHT-induced N-cadherin (mesenchymal cell biomarker) and increased expression in cytokeratin 18 and E-cadherin (epithelial cell biomarkers) in these cells. AR signaling is known to play an important role in stimulating DHT-induced EMT by stimulating the STAT3/Snail signaling pathway in MDA-MB231. However, results in the present study shows that γ-tocotrienol treatment significantly inhibited activation of STAT3 and Snail proteins. Additional immunocytochemistry experiments showed that γ-tocotrienol treatment significantly inhibited DHT-induced cytoskeleton changes in TNBC MDA-MB-231 and MDA MB-453 cell lines. In conclusion, these results demonstrated that γ-tocotrienol treatment inhibits AR expression and DHT-dependent EMT and cytoskeleton changes in TNBC cells. These findings suggest that AR may be a potential therapeutic target for treating both LAR and non-LAR TNBC subtypes. This study was supported in part by funding from the Louisiana Cancer Foundation. Citation Format: Nayef Aldabaan, Tasmin A. Sultana, Paul W. Sylvester. γ-Tocotrienol inhibition of androgen receptor (AR) expression and activation in triple negative breast cancer (TNBC) MBA-MB-231 and MDA-MB-453 cells is associated with a reduction in epithelial-to-mesenchymal transition (EMT) [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 967.

Abstract 711: γ-Tocotrienol inhibition of androgen receptor (AR) expression and activation in triple-negative breast cancer (TNBC) MDA-MB-453 cells is associated with a reduction in cellular proliferation and viability

Abstract Targeted therapy for triple-negative breast cancer (TNBC) remains challenging due to poor understanding of its molecular etiology. Previous studies have shown that androgen receptors (AR) are widely expressed in approximately one-third of TNBC, and are referred to as luminal androgen receptors (LAR). AR has recently emerged as a prognostic and treatment-predictive biomarker in breast cancer. However, the role of AR in TNBC remained elusive. Treatment with AR-antagonist have been shown to suppress AR activation and signaling in TNBC and results in a corresponding reduction in tumor cell proliferation and survival due to the initiation of apoptosis in these tumor cells. γ-Tocotrienol (γT3) is a natural isoform of vitamin E that displays potent anticancer activity. Results show that treatment with 0-7 μM γT3 induces a dose-responsive significant decrease, whereas treatment with 35 nM dihydrotestosterone (DHT) results in a significant increase of AR expression and corresponding increase in growth of MDA-MB-453 TNBC cells. Combined treatment of 7 μM γT3 with 35 nM DHT significantly inhibits DHT-induced proliferation and AR activation in MDA-MB-453 cells. Western blot analysis shows that combined treatment with γT3 and DHT induced a significant decrease in phosphorylated ERK1/2 (active form) expression, but had no effect on total ERK1/2 levels in MDA-MB-453 TNBC cells. Flow cytometry analysis shows that γT3 treatment was also found to induce G0/G1 cell cycle arrest and significantly increased the number of apoptotic and necrotic cells, as compared to MDA-MB-453 TNBC cells in the vehicle-treated control group. Western blot analysis shows that γT3 treatment also inhibited DHT-induced elevations in CDK2, CDK4, CDK6 and cyclin D1 expression (cell cycle progression biomarkers) and induces a significant increase in the expression of tumor suppressor protein, p53, in MDA-MB-453 TNBC cells. Similar treatment with 7 µM γT3 induces a corresponding significant increase in apoptosis biomarker expression of cleaved caspase-3 and Bax in MDA-MB-453 TNBC cells. In summary, results from these studies demonstrated that γT3 treatment inhibits AR expression, activation and signaling, as well as DHT-dependent cell proliferation and viability in TNBC. These finding also suggest that the LAR may be a potential therapeutic target for the treatment TNBC. This study was supported in part by funding from the Louisiana Cancer Foundation. Citation Format: Tasmin A. Sultana, Nayef Aldabaan, Paul W. Sylvester. γ-Tocotrienol inhibition of androgen receptor (AR) expression and activation in triple-negative breast cancer (TNBC) MDA-MB-453 cells is associated with a reduction in cellular proliferation and viability [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 711.

Abstract 954: Combined treatment of γ-tocotrienol, and vitamin D3 synergistically inhibits breast cancer cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT)

Abstract Metastatic breast cancer is a leading cause of death of women in the United States. The metastatic process involves epithelial cells losing their cellular polarity, adhesion to the basement membrane, and acquiring migratory and invasive properties. Metastatic epithelial cells take on a mesenchymal phenotype, hence this process is termed epithelial-to-mesenchymal transition (EMT). EMT is characterized by a reduction in epithelial cell marker expression (E-cadherin, cytokeratin 8, and cytokeratin 18), and an increased expression of mesenchymal cell markers (N-cadherin, vimentin, and fibronectin). Previous studies have demonstrated that dietary intake of γ-tocotrienol and/or vitamin D3 may provide benefit in the preventing the growth and development of metastatic breast cancer. γ-Tocotrienol is a natural isoform of vitamin E that shows potent anticancer activity against a variety of cancer cell types at treatment doses that have little or no effect on normal cell growth or viability. Vitamin D3 has also been shown to display potent antiproliferative and antiangiogenic activity against human breast cancer cells, particularly triple negative breast cancers. Studies were conducted here to examine the effects of γ-tocotrienol and vitamin D3 given alone or in combination on MDA-MB-231 triple negative breast cancer (TNBC) cellular proliferation, migration, and epithelial to mesenchymal transition. Treatment with 10-16 µM γ-tocotrienol or 20-40 nM vitamin D3 induced a significant dose-responsive decrease in MDA-MB-231 growth after a 4-day culture period. Combined treatment with sub-effective doses of γ-tocotrienol (8 μM) and vitamin D3 (10 nM) induced a synergistically inhibition of MDA-MB-231 cell growth, as determined isobologram analysis. Studies using the matrigel invasion assay showed that similar combination treatment with subeffective doses of γ-tocotrienol and vitamin D3, significantly inhibited MDA-MB-231 motility. These effects appear to result from a reversal in EMT. Western blot analysis shows that combined treatment resulted in an increased expression of the epithelial cell markers E-cadherin, cytokeratins 8 and cytokeratins 18 and a corresponding reduction in mesenchymal cell markers N-cadherin and vimentin. Taken together, these findings indicate that combined treatment with subeffective doses of γ-tocotrienol and vitamin D3 synergistically inhibit TNBC MDA-MB-231 breast cancer cell growth, viability, motility, and induced a reversal of EMT. These findings strongly suggest that combined γ-tocotrienol and vitamin D3 treatment may provide significant benefits in the treatment of metastatic TNBC in women. This study was supported in part by funding from the Louisiana Cancer Foundation. Citation Format: Md. Rafi Anwar, Taylor A. Hurst, Paul W. Sylvester. Combined treatment of γ-tocotrienol, and vitamin D3 synergistically inhibits breast cancer cell proliferation, migration, and epithelial-to-mesenchymal transition (EMT) [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 954.

Geographic determinants of colorectal cancer in Louisiana

PurposeCurrently, rural residents in the United States (US) experience a greater cancer burden for tobacco-related cancers and cancers that can be prevented by screening. We aim to characterize geographic determinants of colorectal cancer (CRC) incidence in Louisiana due to rural residence and other known geographic risk factors, area socioeconomic status (SES), and cultural region (Acadian or French-speaking).MethodsPrimary colorectal cancer diagnosed among adults 30 years and older in 2008–2017 were obtained from the Louisiana Tumor Registry. Population and social and economic data were obtained from US Census American Community Survey. Rural areas were defined using US Department of Agriculture 2010 rural–urban commuting area codes. Estimates of relative risk (RR) were obtained from multilevel binomial regression models of incidence.ResultsThe study population was 16.1% rural, 18.4% low SES, and 17.9% Acadian. Risk of CRC was greater among rural white residents (RR Women: 1.09(1.02–1.16), RR Men: 1.11(1.04–1.18)). Low SES was associated with increased CRC for all demographic groups, with excess risk ranging from 8% in Black men (RR: 1.08(1.01–1.16)) to 16% in white men (RR: 1.16(1.08–1.24)). Increased risk in the Acadian region was greatest for Black men (RR: 1.21(1.10–1.33)) and women (RR: 1.21(1.09–1.33)). Rural–urban disparities in CRC were no longer significant after controlling for SES and Acadian region.ConclusionSES remains a significant determinant of CRC disparities in Louisiana and may contribute to observed rural–urban disparities in the state. While the intersectionality of CRC risk factors is complex, we have confirmed a robust regional disparity for the Acadian region of Louisiana.

The Impact of Obesity on Patients with Hepatocellular Cancer in Louisiana

The Impact of Obesity on Patients with Hepatocellular Cancer in Louisiana

Bayesian variable selection for the Cox regression model with spatially varying coefficients with applications to Louisiana respiratory cancer data.

The Cox regression model is a commonly used model in survival analysis. In public health studies, clinical data are often collected from medical service providers of different locations. There are large geographical variations in the covariate effects on survival rates from particular diseases. In this paper, we focus on the variable selection issue for the Cox regression model with spatially varying coefficients. We propose a Bayesian hierarchical model which incorporates a horseshoe prior for sparsity and a point mass mixture prior to determine whether a regression coefficient is spatially varying. An efficient two-stage computational method is used for posterior inference and variable selection. It essentially applies the existing method for maximizing the partial likelihood for the Cox model by site independently first and then applying an Markov chain Monte Carlo algorithm for variable selection based on results of the first stage. Extensive simulation studies are carried out to examine the empirical performance of the proposed method. Finally, we apply the proposed methodology to analyzing a real dataset on respiratory cancer in Louisiana from the Surveillance, Epidemiology, and End Results (SEER)program.

Abstract 2573: The anticancer effects of the vitamin E isoform, γ-tocotrienol, and vitamin D3 act synergistically to inhibit MDA-MB-231 triple negative breast cancer (TNBC) cell proliferation and viability in vitro

Abstract Epidemiological studies suggest that dietary intake of some natural products may be effective in reducing the risk of breast cancer. Furthermore, various phytochemicals have been shown to interfere with cell signaling pathways involved in regulating breast cancer cell proliferation and viability. γ-Tocotrienol is a natural isoform of vitamin E that displays potent anticancer activity against a variety of cancer cell types at treatment doses that have little or no effect on normal cell growth or viability. Vitamin D3 is an abundant phytochemical which also displays potent antiproliferative and antiangiogenic activity against human breast cancer cells. Studies were conducted to examine the effects of γ-tocotrienol and vitamin D3 given alone or in combination on MDA-MB-231 triple negative breast cancer (TNBC) cellular proliferation, migration, colony formation, invasion, cell cycle progression, and apoptosis. Results showed that combined treatment with subeffective doses of γ-tocotrienol (8 μM) and vitamin D3 (10 nM) synergistically inhibited the growth of MDA-MB-231 cells, as determined by the MTT assay and isobologram analysis. Additional studies indicated that this combination treatment resulted in a significant inhibition in cancer cell migration and a significant reduction in cancer cell colony formation. Studies using the Matrigel invasion assay showed that combined treatment with subeffective doses of γ-tocotrienol and vitamin D3, significantly inhibited MDA-MB-231 invasiveness. Flow cytometry analysis showed that similar combined treatment of γ-tocotrienol and vitamin D3 significantly increased the percentage of cells found in G0/G1 phase, as compared to cells in the vehicle-treated control group. After 4 days of combined treatment with subeffective doses of γ-tocotrienol and vitamin D3, the percentage of cells in the G0/G1 phase of the cell cycle increased to 55% (p&amp;lt;0.05, all p values compared to untreated cells), as compared to 37.48% for cells in the vehicle-treated control group. In addition, combination treatment with subeffective doses of γ-tocotrienol and vitamin D3, significantly increased the number of apoptotic and necrotic cells, as comparted to cells in the vehicle-treated control group. In summary, these findings indicate that combined treatment with subeffective doses of γ-tocotrienol and vitamin D3 act synergistically to inhibit MDA-MB-231 human breast cancer cell growth and viability, and strongly suggest that combined treatment with these agents may provide some benefits in the treatment of TNBC in women. This study was supported in part by funding from the Louisiana Cancer Foundation. Citation Format: Md. R. Anwar, A.K.M.N. Hossian, Georgios Matthaiolampakis, Paul W. Sylvester. The anticancer effects of the vitamin E isoform, γ-tocotrienol, and vitamin D3 act synergistically to inhibit MDA-MB-231 triple negative breast cancer (TNBC) cell proliferation and viability in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2573.

“Waiting to Die”: Toxic Emissions and Disease Near the Denka Performance Elastomer Neoprene Facility in Louisiana's Cancer Alley

Background: Residents of census tract 708 in St. John Parish, Louisiana, face the highest nationwide cancer risk from air pollution due to chloroprene emissions from the Denka Performance Elastomer facility. The University Network for Human Rights worked with residents of this predominantly Black community in Cancer Alley to design and implement a survey-based health study of the area. The study aimed to (1) assess the relationship between household proximity to the facility and reported illness, and (2) advance the advocacy objectives of the community. Methods: The survey area consisted of households within a 2.5-km radius of the Denka facility. Sixty percent of the households within 1.5 km of the facility (“Zone 1”) and 20% of the households between 1.5 and 2.5 km from the facility (“Zone 2”) were randomly sampled. Survey implementers collected information on cancer diagnoses about all residents of each surveyed household. Information on chloroprene-linked medical symptoms was collected about respondents (those who took the survey) only. Results: Cancer prevalence among the survey sample is (1) significantly higher than what is considered likely using Monte Carlo simulations based on Surveillance, Epidemiology, and End Results prevalence data (p = 0.0306); and (2) associated with proximity to the facility, with significantly higher-than-likely prevalence in Zone 1 (p = 0.0032) and lower prevalence in Zone 2. Levels of medical symptoms among respondents are high and also associated with proximity to the facility. Discussion: Our findings highlight the need for action to compel Denka to reduce chloroprene emissions to Environmental Protection Agency-recommended limits. Conclusion: Our findings are consistent with Cancer Alley communities' lived experiences of the debilitating health consequences of the area's industrial emissions. The burden of proof must shift to polluting industries.

Women diagnosed with heptocellular cancer in louisiana have higher rates of treatment and better survival compared to men

Presenter: Andrea Fa MD | Louisiana State University Health Science Center Background: Hepatocellular cancer (HCC) is a male-dominated disease, and clinicopathologic characteristics of women with HCC remain poorly defined. Louisiana ranks 5th in HCC incidence and 2nd in HCC mortality in the United States. We sought to better understand gender differences amongst HCC patients in Louisiana - one of the highest incidence and mortality states in the nation. Methods: HCC patients diagnosed in Louisiana between 2005 and 2015 were identified from the Louisiana Tumor Registry (LTR) using ICD-3-O primary site code 220 and histology codes 8170-8180. We excluded cases diagnosed by death certificate/autopsy and those for which HCC was not the patient’s first tumor. Incidence, demographics, treatment, and outcomes were compared between men and women. Patient clinicopathologic characteristics were compared using two-sample t-tests and chi-square tests. HCC-specific survival was analyzed via Cox proportional hazard models. Results: 2,627 patients were included in the analysis, 498 (19%) were women. During the study period, age-adjusted incidence of HCC was 15.8 per 100,000 men and 3.5 per 100,000 women . Women were older (65.1 vs. 61.3, p < 0.0001), but were more often diagnosed with early stage disease (AJCC I or II) (p = 0.0224) than men. The severity of comorbidities was not different between women and men (p = 0.1277). Women were more likely to have received liver-directed surgery (LDS) (27.5% vs. 22%, p = 0.009). Women had improved survival when compared to men (HR (95% CI): 1.15 (1.02,1.29)), after adjusting for stage, age, race, comorbidity score, and treatment location. This survival difference was no longer significant after controlling for LDS (HR (95% CI): 1.09 (0.97,1.22)). Multivariable factors associated with worse survival in women were advanced stage (p < 0.0001), treatment location (p < 0.0001) and no LDS (p < 0.0001). There was no affect on survival in women due to race or age as there was in men (See Table 1). Conclusion: There are significant clinicopathologic differences between the men and women with HCC. Women are diagnosed at an earlier stage, they have a greater likelihood of having LDS, and they have improved survival compared to men. These data can be used to direct public health resources to the most at-risk groups.

Multivariate mortality analyses in COVID-19: Comparing patients with cancer and patients without cancer in Louisiana.

This is the largest and only multivariate study evaluating the difference in mortality from coronavirus disease 2019 (COVID-19) between patients with cancer and patients without cancer in the United States. The objective was to assess COVID-19 mortality rates in patients with cancer versus patients without cancer and uncover possible statistically significant characteristics contributing to mortality. This retrospective study analyzed patients with cancer and patients without cancer who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 1 through April 30, 2020. This was a multicenter study in the state of Louisiana throughout the Ochsner Health System in both tertiary and nontertiary centers. Patients older than 18 years were eligible. Three hundred twelve patients with cancer were compared with 4833 patients without cancer. Mortality was found to be higher in the cancer group. Patients of advanced age with cancer had a significant increase in mortality (odds ratio [OR], 5.96; P < .001). Other significant risk factors for increased mortality were male sex (OR, 2.15), a history of chronic kidney disease (OR, 3.84), and obesity (OR, 1.30). In hospitalized patients with cancer, adverse vital signs on admission, decreased absolute lymphocyte counts, thrombocytopenia, elevated creatinine, lactic acidosis, and elevated procalcitonin all seemed to increase the risk of death. Among patients with cancer, active or progressive disease (P < .001) and recent therapy (OR, 2.34; 95% confidence interval, 1.08-5.08) were shown to increase mortality. Patients with cancer have increased mortality in the setting of infection with SARS-CoV-2 in comparison with patients without cancer. Patients with cancer who are 65 years of age or older and those with certain comorbidities have the greatest risk of death. Recent cancer-directed therapy and disease status also seem to play roles in mortality. This is the largest study of patients with cancer versus patients without cancer to date and is the first multivariate analysis study comparing these 2 patient populations. This study confirms the hypothesis that patients with cancer are at increased risk for mortality and that there are multiple characteristics posing the potential to risk-stratify these patients in the setting of a future outbreak.

A Comparison of Bayesian Accelerated Failure Time Models with Spatially Varying Coefficients

The accelerated failure time (AFT) model is a commonly used tool in analyzing survival data. In public health studies, data is often collected from medical service providers in different locations. Survival rates from different locations often present geographically varying patterns. In this paper, we focus on the accelerated failure time model with spatially varying coefficients. We compare three different types of priors for spatially varying coefficients. A model selection criterion, logarithm of the pseudo-marginal likelihood (LPML), is employed to assess the fit of the AFT model with different priors. Extensive simulation studies are carried out to examine the empirical performance of the proposed methods. Finally, we apply our model to SEER data on prostate cancer in Louisiana and demonstrate the existence of spatially varying effects on survival rates from prostate cancer.

Abstract 5015: γ-Tocotrienol inhibition of metastatic phenotypic behavior is associated with a decrease in galectin-3 expression and distribution in the highly malignant mouse +SA mammary tumor cells

Abstract γ-Tocotrienol is a rare natural isoform of vitamin E that displays potent apoptotic and anti-metastatic activity against breast cancer. Galectin-3 is a protein that plays an important role in metastasis by binding to glycoconjugates on receptors and extracellular matrix proteins. Studies were conducted to investigate the effects of γ-tocotrienol on galectin-3 expression and activity in highly malignant mouse +SA mammary tumor cells. Computer-aided molecular modeling studies were carried out within the active site of galectin-3 based on the crystal structure (5EXO) obtained from the protein data bank with a known ligand, and anticancer agents (salirasib, γ-tocotrienol, and β-lactose) galectin-3 docking scores and amino acid interactions were determine. Treatment effects on galectin-3 expression and distribution was determined by Western blot analysis and immunocytochemical fluorescent staining, respectively. Treatment effects on +SA cellular migration and invasion was also determined. Results show that salirasib and β-lactose (known inhibitors of galectin-3) that share some pharmacophoric properties with γ- tocotrienol, with protein docking studies showing that salirasib (active binding -2.8) and γ- tocotrienol (active binding -2.87) had a similar binding score and binding moieties. Western blot analysis shows that γ-tocotrienol treatment induces a downregulation of galectin-3 expression, whereas immunocytochemistry studies shows that galectin-3 is highly expressed in +SA cells, and treatment with 5 μM γ-tocotrienol greatly reduced galectin-3 expression in these cells. Furthermore, galectin-3 was found to form globular structures on the outer membrane of +SA cells in the vehicle-treated control group, and +SA group, and a high level of fibronectin on the outside of +SA cells, and γ-tocotrienol greatly attenuated galectin-3 expression and distribution in +SA cells. Furthermore, treatment with 1.5 μM histamine significantly stimulated +SA mammary tumor cell migration, whereas combined treatment with 5 μM γ-tocotrienol completely blocked histamine-induced +SA cell migration. In summary, these results demonstrate for the first time that γ-tocotrienol treatment inhibits extracellular galectin-3 expression and disrupts galectin-3 carbohydrate binding, activation and migration of +SA mammary tumor cells. These findings also suggest that γ-tocotrienol may provide significant benefits in the prevention and/or treatment of metastatic breast cancer. This study was supported in part by funding from the Louisiana Cancer Foundation. Citation Format: Paul William Sylvester, Jessie Grazier, Mohammed R. Anwar. γ-Tocotrienol inhibition of metastatic phenotypic behavior is associated with a decrease in galectin-3 expression and distribution in the highly malignant mouse +SA mammary tumor cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5015.

Do rural patients with operable breast cancer fare worse than urban patients in Louisiana? Results of the Louisiana cancer consortium

BackgroundIt is unknown whether rural patients with operable breast cancer do worse than urban patients in Louisiana. We performed an analysis of breast cancer based on rural versus urban residencies and evaluate factors associated with worse survival. MethodsData on women diagnosed with stages I to III breast cancer from 2004 to 2016 were obtained from the Louisiana Tumor Registry. Overall survival and cancer-specific survival were compared between rural and urban residencies by sociodemographic, clinical-pathologic, and treatment variables. Kaplan-Meier method and the log-rank test were used to compare the survival curves. Cox regression model was used to assess independent factors associated with overall survival and cancer-specific survival. ResultsOf the 27,780 patients, 2,441 patients (8.7%) resided in rural areas. Compared with urban patients, rural patients tended to be older, underinsured, more impoverished, less likely to be treated at an American College of Surgeons accredited institution, and more likely to be treated at a low-volume center (P < .005 each). For stages I and II diseases, there was a statistically significant difference in overall survival favoring urban regions, but no difference in cancer-specific survival. For stage III disease, there was no difference in either overall survival or cancer-specific survival between the 2 cohorts. Overall survival and cancer-specific survival curves for the entire cohort were not different at the 5-year mark, but become statistically significant with greater time; although rural patients had a lower long-term overall survival (P = .0001) and cancer-specific survival (P = .049) compared with urban patients, the rural-urban differences in overall survival and cancer-specific survival were no longer different after adjusting for other covariates, indicating the observed differences in univariate analysis were attributable to sociodemographic, clinicpathologic, and treatment factors. ConclusionDespite rural patients with operable breast cancer having an overall lesser overall survival and cancer-specific survival than their urban counterpart, rural residence itself was not an independent predictor of outcome. In fact, particular socioeconomic factors increased the risk of death among patients residing in rural areas. Additional analysis at the patient-level is needed to understand the interactions between rurality and breast cancer outcomes in Louisiana.