bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P6-02-01: Screening mammography in women over age 75: Is it beneficial?
Authors: Cate SP , Kohli MK , Gillego A , Chadha M , Fulop T , Boolbol SK
Published: May 2016

Background:

In 2015 the U.S. Preventive Services Task Force (USPSTF) stated that there was insufficient evidence for the use of screening mammography in women aged 75 and older. This statement was based on the lack of randomized controlled trials demonstrating survival benefit in this population. As per the American College of Radiology, the acceptable cancer detection rate via screening mammography is at least 2.5 cases per 1000 examinations for an institution, with reported rates as high as 4.7 cases per 1000.

Aim:

In this study, we sought to examine our institution's practice of screening mammography for women 75 years and older. We aimed to determine the incidence of cancer detection in this age group through screening mammography.

Methods:

A search was performed to identify women aged 75 and above who underwent screening mammography at Mount Sinai Beth Israel Medical Center between January 1, 2013 and December 31, 2014. Patients classified as BIRADS 0 on initial screening were reclassified based on their subsequent diagnostic imaging, if performed. A chart review was performed for those patients who underwent breast biopsies to obtain their pathology results.

Results:

In this two year period, 2057 patients aged 75 and older underwent screening mammography. The majority of women in this age group had non-actionable results of their screening mammography, and were classified as BIRADS 1 or 2 (96%). There were a total of 49 patients who had BIRADS 3 final results (2.4%). Twenty-two patients had screening mammograms that were classified as BIRADS 4 (1.1%). Biopsies revealed 6 invasive ductal carcinomas, 4 cases of in situ carcinoma, 2 cases of duct ectasia, 2 intraductal papillomas, 3 fibrocystic biopsies, and 3 fibroadenomas. In total, 10 of 2057 patients were diagnosed with breast cancer (0.5%).

Mammography results from 2013-2014Final radiologic classificationNumber of patientsPercent of populationBIRADS 182940.3%BIRADS 2114755.7%BIRADS 3492.4%BIRADS 4221.1%BIRADS 500%BIRADS 0100.5%Total screening mammograms2057 

Conclusions:

In our institution, 98.4% of women aged 75 and older had screening mammography with benign results. Ten women in this group were found to have breast cancer. The breast cancer detection rate in this cohort was 4.9 per 1000 screening examinations, which is nearly double the cited recommendation put forth by the American College of Radiology. These results are certainly relevant when considering appropriateness of annual screening mammography in this age group.

Citation Format: Cate SP, Kohli MK, Gillego A, Chadha M, Fulop T, Boolbol SK. Screening mammography in women over age 75: Is it beneficial?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-02-01.
Abstract P6-11-06: Time and value of chemotherapy administration burden in a Swedish hospital
Authors: Nilsson A , Lundkvist J , Lindman H
Published: May 2016

Background

Administration of treatment for cancer patients can require substantial health care resources and differences in administration burden between treatments are therefore important to take into account when comparing them. Besides the direct personnel and bed time, the administration can also have broader consequences on the organisation and process of care delivery, as well as on the patients. How to value differences in these parameters is however not straightforward.

Nab-paclitaxel and paclitaxel are examples of two treatments with important differences in administration burden, and the objective of this study was to perform a time-motion study to compare time required for treatment administration.

Material and methods

Breast cancer patients vising the oncology day care unit at the department of oncology at Akademiska Hospital in Uppsala, Sweden, as part of their regular treatment-course with nab-paclitaxel (n=13) or paclitaxel (n=9) were included in the study.

Time data collection was based on a questionnaire answered by hospital staff. Time for infusions and the total patient time in hospital were measured for each patient.

Results

Mean infusion times per administration of nab-paclitaxel and paclitaxel were 42.1 (Standard deviation (SD) 20.7) minutes and 104.3 (SD 43.3) minutes, respectively. Total patient times in clinic per infusion were 82.2 (SD 40.9) minutes and 183.9 (SD 34.8) minutes, respectively.

A 12-week treatment course of nab-paclitaxel (every three weeks), nab-paclitaxel (weekly) and paclitaxel (weekly) would require in total 2.8, 8.4 and 20.9 hours of infusion time, respectively. The corresponding patient time in hospital would be 5.5, 16.4 and 36.8 hours, respectively.

Conclusion

There can be substantial differences in nurse and facility resources required for administration of chemotherapy, our data showed approximately a 7-fold difference in patient, personnel and facility time requirements between the compared treatments.

In a time with shortage of both hospital personnel and facilities, the valuation of these resources is not easy and may have broader impact on the organisation and delivery of care. Monetary valuation using rent cost or salaries may in a time of resource shortage underestimate the true opportunity cost, and more research and discussions on how to prioritise use of these resources versus other costs are therefore needed.

Citation Format: Nilsson A, Lundkvist J, Lindman H. Time and value of chemotherapy administration burden in a Swedish hospital. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-11-06.
Abstract P6-17-09: Whole brain radiation therapy (WBRT) with or without concurrent temozolomide for brain metastases in breast cancer patients
Authors: El-Sadda WM , Abdel-Halim II , El-Ibrashi MM , Magdi MM
Published: May 2016

Background:

Breast cancer remains the second leading cause of CNS metastases. HER2 positive and triple negative subtypes are especially and independently at higher risk of developing brain metastases. Although surgical resection and radiosurgery may play a role in the management of selected cases, whole brain radiation therapy remains the standard treatment but with limited efficacy. Temozolomide (TMZ); an oral alkylating agent that cross the blood brain barrier has shown radiosensitizing characteristics as well as synergistic effects of radiation therapy (RT).

The aim of the study was to assess the efficacy and safety of WBRT with concomitant TMZ in treatment of brain metastases in breast cancer patients.

Patients and methods:

A prospective randomized study included 60 patients with newly diagnosed brain metastases (BMs) from breast cancer not candidate for surgical resection or radiosurgery. All patients received WBRT 30 Gy/10 fractions with or without TMZ, administered at a dosage of 75 mg/m2/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment defined as partial response (PR) or complete response (CR) on brain MRI (WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurological symptoms and tolerability.

Results:

Between October 2011 and October 2013, 60 patients were enrolled in the study, 30 patients received WBRT+TMZ (group A) and 30 patients received WBRT (group B). Median age was 54 years (30-65), median follow up was 10.4 months (3-36). ORR was 80% in the WBRT+TMZ arm versus 50% in the WBRT (p = 0.017). The median PFS were 11.8 versus 5.8 respectively (p = 0.005). The median OS was 13.8 for group A and 10.8 for group B (p = 0.59). WBRT+TMZ was well tolerated with mostly grade 2 non-hematologic toxicity; headache, nausea & vomiting were 6%, 15% & 12% in group A versus 12%, 9% & 6% in group B, respectively. While the most evident hematologic toxicity recorded was lymphopenia grade 2 & 3 (15% & 12% in group A) and (12% & 9% in group B). No grade 4 toxicities were noted.

Conclusion:

WBRT plus TMZ improve local control and response rate of BMs from breast cancer, which was reflected by improved PFS.

Citation Format: El-Sadda WM, Abdel-Halim II, El-Ibrashi MM, Magdi MM. Whole brain radiation therapy (WBRT) with or without concurrent temozolomide for brain metastases in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-09.
Abstract PD2-07: Insulin receptor substrate (IRS) targeting by the tyrophostin NT157 inhibits breast cancer cell growth
Authors: Yee D , Temiz NA , Levitzki A , Yang Y
Published: May 2016

Insulin and insulin-like growth factor (IGF) signaling systems regulate the malignant phenotype. However, targeting of the type I IGF receptor (IGF-IR) has shown little activity in clinical trials. One potential reason for these disappointing results is that activation of the closely related insulin receptor (InR) could compensate for IGF-IR blockade. Since both receptors phosphorylate the insulin receptor substrates (IRS), perhaps a better strategy would involving targeting of this key post-receptor protein. Two IRS proteins are expressed in breast cancer cells. IRS-1 is regulated by estradiol in breast cancer cell lines, while IRS-2 is the predominant IRS species in hormone receptor negative cells. NT157, a small-molecule tyrphostin, binds IGF-1R but does not affect receptor autophosphorylation. Instead, it downregulates IRS proteins in several model systems. In primary breast cancers, IRS-1 was positively correlated to ERα expression in the TCGA database. In ERα+ and basal-like breast cancer cell lines NT157 treatment suppressed IRS protein expression in a dose dependent manner. Short term exposure to NT157 treatment did not affect IGF-I, IGF-II, and insulin induced activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), but longer exposure resulted in inhibition of these signaling pathways. NT157 resulted in serine phosphorylation of IRS proteins and was dependent on MAPK activation. Serine phosphorylation resulted in disassociation between IRS proteins and their receptors resulting in IRS degradation. NT157 decreased S phase fraction, monolayer, and anchorage independent growth after IGF/insulin treatment in ERα+ breast cancer cells. NT157 downregulation of IRS protein expression also sensitized ERα+ breast cancer cells to rapamycin. Moreover, NT157 inhibited the growth of tamoxifen resistant ERα+ breast cancer cells. In the basal-like breast cancer cells (MDA-MB-231), NT157 repressed the proliferation (G2/M abrogation) and migration through downregulation of IRS1/2 protein. Given that both IGF-IR and InR play a role in cancer biology, targeting of IRS adapter proteins could be a more effective inhibitory strategy compared to receptor-targeting approaches.

Citation Format: Yee D, Temiz NA, Levitzki A, Yang Y. Insulin receptor substrate (IRS) targeting by the tyrophostin NT157 inhibits breast cancer cell growth. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD2-07.
Abstract PD3-05: Inhibition of fatty-acid oxidation as a therapy for triple-negative breast cancer
Authors: Goga A , Camarda R , Zhou AY , Kohnz RA , Balakrishnan S , Anderton B , Mahieu C , Eyob H , Krings G , Nomura DK
Published: May 2016

Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC) compared to estrogen, progesterone and/or human epidermal growth factor 2 receptor-positive (RP) breast tumors. We and others have shown that MYC alters metabolism during tumorigenesis. However, the role of MYC in TNBC metabolism remains largely unexplored. We hypothesized that pharmacologic inhibition of MYC-driven metabolic pathways may serve as a therapeutic strategy for this clinically challenging subtype of breast cancer. Using an unbiased metabolomics approach, we identified fatty acid oxidation intermediates as dramatically up-regulated in MYC-driven models of TNBC. A lipid metabolism gene signature was identified in patients with TNBC in the TCGA and multiple other clinical datasets, implicating fatty acid oxidation as a deregulated pathway critical for TNBC metabolism. We find that MYC-overexpressing TNBC, including transgenic models and patient-derived xenografts (PDX), display increased bioenergetic reliance upon fatty-acid oxidation (FAO). Pharmacologic inhibition of FAO catastrophically decreases energy metabolism of MYC over-expressing breast cancer, blocks growth of a MYC-driven transgenic TNBC model and MYC-overexpressing patient-derived xenografts. In vivo inhibition of FAO induced proliferation arrest and increased cell death in PDX models of TNBC. Our results demonstrate that inhibition of FAO is a novel therapeutic strategy against TNBCs that over-express MYC.

Citation Format: Goga A, Camarda R, Zhou AY, Kohnz RA, Balakrishnan S, Anderton B, Mahieu C, Eyob H, Krings G, Nomura DK. Inhibition of fatty-acid oxidation as a therapy for triple-negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD3-05.
Abstract PD6-06: Somatic mutation patterns differentially affect survival in breast cancer molecular subtypes
Authors: Gyorffy B , Pongor L , Szabo A , Bottai G , Pusztai L , Santarpia L
Published: May 2016

Background: The prognostic effects of somatic gene mutations and correlated gene expression in breast cancer is argument of debate. In this study we analyzed the impact of specific mutations on gene expression and their relevance in the prognosis of breast cancer subtypes.

Materials and methods: Exome sequencing and RNA-seq data obtained from TCGA were analyzed. Data was processed using MuTect, MapSplice and RSEM. All together data from 757 patients (ER-/HER2- [n=143], HER2+ including ER positive and negative patients, [n=136], and ER+/HER2- [n=478]) were included. Univariate Receiver Operating Characteristic (ROC) analysis was performed for the top mutated genes (mutated in at least 5% of patients) using the ROC Bioconductor library in R to identify genes whose expression was significantly associated with a mutation. Then, the mean expression of the significant genes was designated as a metagene for each genotype. We assessed the correlation with survival for each metagene by Cox proportional hazards regression and by plotting Kaplan-Meier survival plots. A significance threshold of p<1E-04 was set for each gene to be considered in the survival analysis, and only the top 100 genes were used when there were more than 100 genes significant.

Results: In the overall population only few mutated genes including TP53 (HR=1.66), CDH1 (HR=0.61), AKT1 (HR=0.54), ATM (HR=1.76), NF1 (HR=0.58), KMT2D (HR=2.32), and UBR5 (HR=1.94) were significantly associated with survival. In ER-/HER2- mutant samples the PIK3CA (HR=2.79) and MAP3K1 (HR=2.98), and in HER2+ mutant samples the ARID1A (HR=0.26) and PIK3CA (HR=0.27) metagenes were associated with survival, respectively. Overall, using the combined metagene the majority of the significant mutated genes retained their prognostic power. Mutations of specific genes impacted their own expression and prognosis. The expression of TP53 (AUC=0.609, p=2.60E-06), and MAP3K1 (AUC=0.617, p=6.07E-03) was higher in samples with a mutation while the expression of CDH1 (AUC=0.684, p=2.72E-07), PTEN (AUC=0.687, p=1.47E-04), and BRCA1 (AUC=0.608, p=2.24E-02) was lower.

Conclusions: Our finding support that specific mutated genes may differentially impact prognosis in breast cancer subtypes. Further efforts are required to understand the biological and prognostic role of specific activating and inactivating mutations across molecular breast cancer subtypes.

Citation Format: Gyorffy B, Pongor L, Szabo A, Bottai G, Pusztai L, Santarpia L. Somatic mutation patterns differentially affect survival in breast cancer molecular subtypes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD6-06.
Abstract A80: The Affordable Care Act dependent coverage expansion and cancer stage at diagnosis among young adults in the United States
Authors: Xiong Ka Zang , Jemal Ahmedin , Han Xuesong
Published: May 2016

Objective: To examine whether the proportion of cancers diagnosed at early stage has increased after the implementation of the Affordable Care Act-Dependent Coverage Expansion provision (ACA-DCE) in 2010, which allows young adults to be covered under their parents' health insurance plan until age 26.

Methods: A total of 44,669 young adults, including 12,016 aged 19-25 and 32,653 aged 26-34, newly diagnosed with cancer in 2007-2009 and 2011-2012 were identified from the 18 registries of the Surveillance, Epidemiology, and End Results Program (SEER). We conducted a difference-in-differences analysis to examine changes in the proportion of stage I disease in young cancer patients aged 19-25 from 2007-2009 (pre-ACA-DCE) to 2011-2012 (post-ACA-DCE), using the corresponding changes in patients aged 26-34 as a control group. Both unadjusted and adjusted linear probability models were fitted for total cancer cases and specific cancer sites controlling for sex, race/ethnicity, absolute age at diagnosis, urban/rural residence, marital status at diagnosis and county-level education.

Results: The uninsured rate (95% confidence interval [95 CI]) in cancer patents aged 19-25 years decreased from 9.9 (8.4, 9.8) % pre-ACA-DCE to 7.7 (6.9, 8.4) % post-ACA-DCE, while it increased from 6.6 (6.2, 6.9) % to 7.2 (6.8, 7.7) % in patients aged 26-34 years. The proportion of stage I disease (95 CI) increased from 51.6 (50.4, 52.8) % to 54.0 (52.9, 55.4) % in patients aged 19-25 years, whereas it decreased from 55.1 (54.4, 55.8) % to 54.9 (54.0, 55.7) % in patients aged 26-34 years, resulting in a net change of 2.6 (0.5, 4.7) percentage-points (P = 0.0155). The net change in multivariate analysis was 2.7 (0.6, 4.8) percentage-points (P=0.0123). When analysis was stratified by specific cancer site, significant changes were confined to carcinoma of cervix and uterus and cases with Osseous & Chondromatous Neoplasms, with an adjusted net change of 11.23 (0.67, 21.79) percentage-points (P=0.0371) and 14.39 (0.3, 28.5) percentage-points (P=0.0453), respectively.

Conclusions: These early observations suggest positive benefits of the ACA-DCE in cancer stage at diagnosis among young adults 19-25 years old. Monitoring cancer outcomes in populations targeted by the ACA will be important for assessing the short- and long-term effects of the policy on population health.

Citation Format: Ka Zang Xiong, Ahmedin Jemal, Xuesong Han. The Affordable Care Act dependent coverage expansion and cancer stage at diagnosis among young adults in the United States. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A80.
Abstract B08: Highlighting the maturation of the MSI/NCI P20 South Carolina Cancer Disparities Research Center Partnership
Authors: Ford Marvella E. , Watson Dennis K. , Stukes James , Ahmed Mahtabuddin , Turner David P. , Knowell Ashley Evans , Findlay Victoria J. , Harrison Anita L. , Knight Kendrea D. , Varner Heidi , Cannady Kimberly , Salley Judith D.
Published: May 2016

The South Carolina Cancer Disparities Research Center (SC CaDRe), funded by the NIH/NCI Center to Reduce Cancer Health Disparities (CRCHD) in 2011, is a formal collaboration between the Medical University of South Carolina (MUSC) and South Carolina State University (SCSU, an historically black university). The SC CaDRe focuses on biological mechanisms of disparity in hormone-related cancers (breast and prostate cancer). The Sea Island population plays a prominent role in the three SC CaDRe research projects. The Sea Islanders are an African American ethnic group indigenous to the coastal southeast, with low rates of European American genetic admixture; as such they are ideal for inclusion in biomedical research. Each SC CaDRe research project includes Multiple PIs from MUSC and SCSU. The first research project is titled Biological Implications of DNA Glycation in Prostate Cancer Disparities; the second is titled MicroRNA Mediated Negative Regulation of Caveolin 1 as a Biological Mechanism Driving Breast Cancer Disparities; and the third is titled Feasibility Study of Breast Cancer Candidate Genes in Three Population Groups in South Carolina. The design and results of each project will be presented. The P20 SC CaDRe has led to two funded NIH R21 grants, an R01 grant, an R25E grant, and a DOD research training grant. Three undergraduate students from SCSU and four graduate students from MUSC have participated in SC CaDRe cancer research training, resulting in peer-reviewed publications and presentations at national scientific meetings. As a next step, the SC CaDRe investigators plan to submit an NIH/NCI CRCHD U54 grant application in 2016.

Citation Format: Marvella E. Ford, Dennis K. Watson, James Stukes, Mahtabuddin Ahmed, David P. Turner, Ashley Evans Knowell, Victoria J. Findlay, Anita L. Harrison, Kendrea D. Knight, Heidi Varner, Kimberly Cannady, Judith D. Salley. Highlighting the maturation of the MSI/NCI P20 South Carolina Cancer Disparities Research Center Partnership. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B08.
Abstract B31: A new approach to targeted therapy for obesity-related pancreatic adenocarcinoma
Authors: Tchio Cynthia Ines Mantho , Harbuzariu Adriana , Harmon Tia L. , Beech Derreck J. , Gonzalez-Perez Ruben R.
Published: May 2016

Background: Obesity is an important risk factor of Pancreatic Adenocarcinoma (PA) and it is characterized by the accumulation of excessive body fat and a Body Mass Index (BMI) value greater than 30. Obesity is also characterized by high levels of leptin, which has been consistently associated with the development of many different cancer including pancreatic cancer. Obesity can also alter the epigenome via epigenetics changes as DNA methylation and histones acetylation. Histone lysine residues can be acetylated by Histone Acetyltransferases or deacetylated by Histone Deacetylases (HDAC). Leptin can induce the proliferation of Pancreatic Cancer Stem Cells (PCSC), which are responsible for chemoresistance, invasiveness and reoccurrence of PA. PCSC express specific cell markers and can form tumorspheres in vitro. Our lab developed a leptin antagonist named LPrA2, which was bound to iron oxide nanoparticle (IONP-LPrA2) in order to increase its effectiveness and bioavailability.

Methods: The adjuvant effects of IONP-LPrA2 in combination of chemotherapeutic drugs on PCSC and tumorspheres formation in low attachment plates were determined. Additionally, the effects of IONP-LPrA2 in combination with chemotherapeutic drugs on the differential expression of epigenetic markers HDAC-1, HDAC-2, and HDAC-8 were investigated. The PA cells were cultured in vitro and treated with leptin, IONP-LPrA2, and chemotherapeutics. Then, the expression of epigenetic and PCSC markers, cell proliferation and survival were determined via Nexcelom cellometer or Guava EasyCyte flow cytometer analyses. Results were assessed by western blot analysis.

Results: Leptin affects the level of some HDACs and PCSC markers. That was abrogated by IONP-LPrA2. Chemotherapeutics showed differential effects on the epigenetic and PCSC markers and on tumorspheres formation by PA cells.

Conclusion: These findings suggest that IONP-LPrA2 could be useful to design new PA therapies in combination with chemotherapeutics. Furthermore, IONP-LPrA2 may increase the efficiency of chemotherapeutic drug Gemcitabine. These results could be most relevant for obese patients that show the highest incidence of PA and lowest survival rate.

Citation Format: Cynthia Ines Mantho Tchio, Adriana Harbuzariu, Tia L. Harmon, Derreck J. Beech, Ruben R. Gonzalez-Perez. A new approach to targeted therapy for obesity-related pancreatic adenocarcinoma. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B31.
Abstract B84: Influence of acculturation, ethnic identity, and Latino origin on barriers to colonoscopy in low-income Latinos: A longitudinal study
Authors: Santiago-Rivas Marimer , Jandorf Lina , DuHamel Katherine
Published: May 2016

Objectives: Colorectal cancer (CRC) screening rates continue to be lower than projected, particularly in Latinos. Fear of colonoscopy preparation and procedure, worry about colonoscopy results, CRC fatalism, CRC preventability and curability, and CRC perceived risk have been identified as CRC screening barriers in Latinos. The study purpose was to examine change in level of fear of colonoscopy, worry, CRC fatalism, preventability, and perceived risk using longitudinal data of Latinos who participated of a randomized control trial to test the impact of a culturally targeted and theoretically based psycho-educational print intervention designed to increase CRC screening via colonoscopy. Participants were assessed with study measures before and at 4- and 8-months after randomization.

Methods: Our sample included 250 Latinos between the ages of 50 and 81 years who had no personal or immediate family history of CRC, no colonoscopy in the past 5 years before participating in the study, received a referral for colonoscopy, and completed a colonoscopy by the end of the study. Interviews were performed, and data were analyzed using repeated measures MANCOVA to control for acculturation level and ethnic identity score, and to conduct group comparisons by Latino origin.

Results: A significant repeated measures MANOVA, F (16, 180) = 4.13, p<.001, showed an overtime decrease in fear of colonoscopy (p<.001), and worry (p<.01). An initial repeated measures MANCOVA, F (16, 173) =1.74, p<.05, showed a significant association between time and ethnic identity, but not with acculturation or Latino origin. A follow-up repeated measures MANCOVA (with ethnic identity as covariate), F (16, 176) =1.79, p<.05, also showed a decrease in fear (p<.05) and worry (p<.05).

Discussion: We found an association between change in fear and worry scores, and ethnic identity. Interventions that address negative emotions regarding CRC screening procedures/results should also consider addressing the influence of individual characteristics (e.g., commitment and sense of belonging to their ethnic group) on CRC screening among Latinos referred to colonoscopy.

Citation Format: Marimer Santiago-Rivas, Lina Jandorf, Katherine DuHamel. Influence of acculturation, ethnic identity, and Latino origin on barriers to colonoscopy in low-income Latinos: A longitudinal study. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B84.
Abstract C24: An integrative review of psychosocial concerns among young African American breast cancer survivors
Authors: Nolan Timiya S. , Frank Jennifer , Gisiger-Camata Silvia , Meneses Karen
Published: May 2016

Background: African American women are more likely to be diagnosed with breast cancer at an early age, more likely to experience morbidity after treatment, and disparities in survivorship. While psychosocial well-being is well known among breast cancer survivors, data are few regarding minorities such as African Americans, particularly those who are young.

Objective: This integrative review examines psychosocial concerns in survivorship among young African American breast cancer survivors (YAABCS) using a holistic quality of life framework.

Methods: Pubmed, CINHAL, and Scopus were searched for articles exploring psychological or social well-being in YAABCS.

Results: The search yielded 264 articles. Thirty-six articles were retrieved and reviewed for relevance. Of these, 14 articles were selected based on inclusion/exclusion criteria. Themes of YAABCS psychosocial concerns were sexuality, mood, social support, and spirituality.

Conclusions: The review demonstrated need for further research in YAABCS quality of life to adapt a more fitting quality of life model and to develop culturally-appropriate survivorship interventions.

Implications for Practice: Clinicians, researchers, and YAABCS must partner to increase knowledge of the multidimensional survivorship of YAABCS. With knowledge, we may be able to decrease health disparities among YAABCS.

The project was funded by an American Cancer Society Doctoral Degree in Nursing Scholarship, Jonas Nurse Leadership Scholarship, and Gladys F. Colvin Doctoral fellowship. Additional support received from a Komen Graduate Training in Disparities Research Award.

Citation Format: Timiya S. Nolan, Jennifer Frank, Silvia Gisiger-Camata, Karen Meneses. An integrative review of psychosocial concerns among young African American breast cancer survivors. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C24.
Abstract C29: Racial disparities in endometrial cancer epidemiology and mortality-to-incidence ratios in South Carolina
Authors: Babatunde Oluwole Adeyemi , Adams Swann Arp , Eberth Jan M. , Wirth Michael D. , Choi Seul Ki , Hebert James R.
Published: May 2016

Background: Endometrial cancer (EC) exhibit striking racial disparities with higher mortality in African Americans (AA) compared to European Americans (EA). The mortality-to-incidence rate ratio (MIR) gives a population based measure for survival which accounts for incidence. The objective of this study was to map EC MIRs by race for eight health regions within South Carolina (SC) and chart EC incidence by race and grade across the four cancer stages.

Methods: Data on EC incidence and deaths were obtained from the South Carolina Central Cancer Registry, and Vital Registry respectively to construct MIRs. ArcGIS 10.1 software was used to map EC MIRs by race for eight health regions within South Carolina. Four classes of MIR were derived using the national MIR for EC among EAs as the reference.

Results: When stratified by tumor stage, AAs had higher levels of poorly differentiated tumors across all stages. The incidence and mortality were consistently higher among AAs. Striking racial differences were observed with incidence and mortality consistently higher among AAs. In all eight health regions, AAs were in the highest MIR category. By contrast, EA MIRs were more evenly represented over the 4 classes.

Conclusions: The MIR proved useful for identifying disparities in EC incidence, mortality and virulence among AA and EA women in SC. Cancer surveillance programs may use the MIR to monitor disparities across racial/ethnic groups and geographic regions going forward. MIRs have the potential to serve as an indicator of the long-term success of cancer surveillance programs.

Citation Format: Oluwole Adeyemi Babatunde, Swann Arp Adams, Jan M. Eberth, Michael D. Wirth, Seul Ki Choi, James R. Hebert. Racial disparities in endometrial cancer epidemiology and mortality-to-incidence ratios in South Carolina. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C29.
Abstract C32: Native American genetic ancestry is protective against prostate cancer in African Americans and European Americans
Authors: Murphy Adam , Batai Ken , Shah Ebony , Kittles Rick A.
Published: May 2016

Prostate cancer (PCa) incidence and mortality varies by racial/ethnic groups in the U.S. African American (AA) men have a 60% higher incidence and twice the mortality rate of European America (EA) men, while Hispanic Americans and Native Americans have lower incidence rates than EA men. Several genetic admixture studies have examined the role of west African ancestry on prostate cancer risk in AA men, however the influence of Native American ancestry on PCa risk has not been explored. Here we evaluated the relationship between individual genetic ancestry proportions and the likelihood of PCa diagnosis and aggressiveness.

Methods: We recruited 40-79 year old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for genotyping of 105 ancestry informative markers. West African, European, and Native American genetic ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the likelihood of having high-risk PCa relative to controls, adjusting for age and family history of PCa.

Results: In AAs, NAA ranged from 0.4% to 28.8%. Mean NAA was 4.6% in AA cases, while controls had mean NAA of 6.6%. NAA ranged from 0.5% to 17.4% in EAs. Mean NAA was 5.1% in cases and 6.8% in controls. NAA was negatively associated with PCa diagnosis. AA men in the highest quartile of NAA had significantly reduced odds of PCa diagnosis compared to men in the lowest quartile of NAA (OR 0.47, 95% C.I.: 0.29-0.77). Similarly, EA men in the highest quartile of NAA had significantly reduced odds of PCa diagnosis compared men in the lowest NAA quartile (OR 0.36, 95% C.I.: 0.21-0.61). Additional adjustment of body mass index, education, smoking, alcohol use, and marital status did not change the results. NAA was also negatively associated with diagnosis of high risk PCa in EAs (P=0.04) and also trending in the same direction in AAs however not significant.

Conclusions: Our study reveals that NAA is protective against PCa diagnosis and high-risk PCa. Hispanic Americans and Native Americans have lower PCa incidence rates than AAs and EAs, and the identification of inherited genetic or environmental factors that are associated with high NAA may improve PCa risk prediction and/or help to develop prevention strategies.

Citation Format: Adam Murphy, Ken Batai, Ebony Shah, Rick A. Kittles. Native American genetic ancestry is protective against prostate cancer in African Americans and European Americans. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C32.
Abstract IA13: Understanding and preventing breast cancer disparities in Latinas
Authors: Thompson Beti , Beresford Shirley AA , Coronado Gloria D. , Neuhouser Marian , Li Christopher I. , Cook Linda S. , Porter Peggy
Published: May 2016

Background: Although Latinas have lower breast cancer rates compared to non-Hispanic Whites (NHW), breast cancer is the top cancer killer of Latinas. There are many reasons for this, some involve biology, types of breast cancer found in Latinas, metabolic increases thought to be due to adoption of western diets, and lack of screening for early detection. In a large breast cancer program examining such cancers in Latinas, we overcame a number of challenges in each of four studies examining the fore-named factors.

Methods: Four projects and four cores made up our Center for Population Health and Health Disparities (CPHHD). Using a community-based participatory research (CBPR) model, we recruited Latinas to participate in studies investigating the various factors related to breast cancer. Projects used robust methodologies to assess the relationship between elevated risks of triple negative breast cancers; the effects of a typical US diet compared to a traditional Mexican diet; the role of genetic ancestry on breast cancer in Latinas; and the effectiveness of a lay health worker intervention to increase breast cancer screening. As part of the program, we asked investigators to identify challenges encountered and how they were resolved.

Results: All four projects were completed on time. Overall results of each project will be presented. Challenges in each project will be described as well as how the challenges were overcome. The role of the Community Advisory Board will be described and how its suggestions for sending results back to participants were adopted and incorporated in the program.

Discussion: Embarking on a large transdisciplinary program to understand Latinas' breast cancer risks and to translate those risks to the population of interest has been stimulating and thought-provoking. Addressing challenges as they emerged and finding solutions required a team effort. By obtaining perspectives from a variety of disciplines, we were able to solve the challenges. This team approach is recommended for similar studies.

Citation Format: Beti Thompson, Shirley AA Beresford, Gloria D. Coronado, Marian Neuhouser, Christopher I. Li, Linda S. Cook, Peggy Porter. Understanding and preventing breast cancer disparities in Latinas. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA13.
Abstract A55: Exosome-associated microRNAs as plasma biomarkers for breast cancer
Authors: Hannafon Bethany N. , Trigoso Yvonne D. , Lum David H. , Welm Alana L. , Dooley William C. , Ding Wei-Qun
Published: May 2016

Introduction: microRNAs are promising candidate biomarkers due to their cancer-specific expression profiles. However, efforts to develop circulating breast cancer biomarkers are challenged by the heterogeneity of microRNAs in the blood. To overcome this challenge, we aimed to develop a molecular profile of microRNAs specifically secreted from breast cancer cells. The key to identifying breast cancer-derived microRNAs relies on capturing and analyzing the contents of exosomes, which are small secretory vesicles that selectively encapsulate microRNAs indicative of their cell of origin.

Methods: Exosomes were collected from the conditioned media of breast cancer cell lines, breast ductal fluids, mouse plasma from patient-derived breast tumor orthotopic xenograft models (PDX), and from human plasma samples. Exosomes were verified by electron microscopy and western blot analysis. Cellular and exosome microRNAs from breast cancer cell lines were profiled by next-generation small RNA sequencing. Plasma exosome populations were selected by immunoaffinity isolation utilizing antibodies against CD63 and MUC1. Exosome microRNA expression was measured by qRT-PCR.

Results: Small RNA sequencing and qRT-PCR analysis showed that several microRNAs are selectively expressed in breast cancer exosomes. Importantly, human breast cancer specific microRNAs were detectable in PDX mouse plasma. The microRNA expression patterns in the MUC1-precipitated plasma exosomes differed between breast cancer patients and control subjects. These results provide a potential new strategy to selectively analyze plasma breast cancer microRNAs that may be indicative of the presence of breast cancer.

Conclusions: Several microRNAs are selectively enriched in breast cancer exosomes, which can be detected in the plasma of PDX mice and breast cancer patients. MUC1 is a viable membrane protein candidate for selective capture of circulating breast cancer specific exosomes from the plasma. These results suggest that selective capture and molecular analysis of breast cancer specific circulating exosomes is a promising strategy for breast cancer biomarker development.

Citation Format: Bethany N. Hannafon, Yvonne D. Trigoso, David H. Lum, Alana L. Welm, William C. Dooley, Wei-Qun Ding. Exosome-associated microRNAs as plasma biomarkers for breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A55.
Abstract A37: Yes-associated protein 1 (YAP) in the growth and tumorigenesis of ovarian granulosa cells.
Authors: Lv Xiangmin , He Chunbo , Hua Guohua , Dong Jixin , Davis John S. , Wang Cheng
Published: May 2016

Ovarian granulosa cells are essential for successful follicle development. Dysregulation of granulosa cell proliferation and differentiation may lead to impairment of female fertility or development of ovarian tumors. Although studies indicate that the Hippo signaling pathway plays critical roles in both development and tumorigenesis of several organs, its role in ovarian physiology and pathology remains largely unknown. The present study aims to investigate the role of YAP in ovarian granulosa cell proliferation, differentiation and transformation. Immunohistochemical analyses showed that the active form of YAP (nuclear YAP) was highly expressed in proliferative granulosa cells, whereas the inactive form of YAP (cytoplasmic YAP) was detected mainly in terminally-differentiated luteal cells, indicating that YAP may be involved in proliferation and differentiation of ovarian granulosa cells. Knockdown of YAP or pharmacological inhibition of YAP activity in human granulosa cells suppressed cell growth and reduced cell survival in both traditional 2D cell culture system and a novel 3D hanging-drop culture system, suggesting that YAP is essential for the growth and survival of human granulosa cells. In addition, ectopic expression of wild-type or constitutively active YAP impaired gonadotropin-induced differentiation of granulosa cells and stimulated the rapid growth and transformation of granulosa cells, findings which were reflected by increased colony formation in soft agar assay and growth of tumors in a xenograft mouse model. Injection of verteporfin (a selective antagonist of YAP) into female CD1 mice inhibited granulosa cell growth, induced GC apoptosis, and disrupted mouse ovarian follicle development, leading to severe subfertility. Consistently, mice with ovarian granulosa cell-specific expression of constitutively active YAP demonstrated disruption of granulosa cell differentiation and failure of ovarian follicle development. In conclusion, our studies demonstrate that homeostatic YAP expression and activation are essential for ovarian granulosa cell proliferation, differentiation and survival. YAP is a novel therapeutic target for treatment of ovarian diseases associated with granulosa cell dysregulation.

Citation Format: Xiangmin Lv, Chunbo He, Guohua Hua, Jixin Dong, John S. Davis, Cheng Wang. Yes-associated protein 1 (YAP) in the growth and tumorigenesis of ovarian granulosa cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A37.
Abstract A58: Bispecific anti-CD3-folate for the treatment of ovarian cancer.
Authors: Xia Jinming , deDios Kristine , Rodrigo Evelyn , Humphreys Robin , Wahl Alan , Gymnopoulos Marco
Published: May 2016

Folic acid receptor 1 (FOLR1, FRα) is highly expressed in 80% of ovarian tumors and has a low nanomolar affinity for folic acid. Although ovarian tumors are intrinsically immunogenic, immune reactions to them are inhibited by a suppressive environment. We are developing a bispecific anti-CD3-folate to redirect T cells to engage with and kill tumor cells. Folic acid was site-specifically conjugated to a FAb fragment of an anti-CD3 antibody through an engineered linkable non-natural amino acid. Anti-CD3-folate bispecific FAb is able to engage T cells and exert cytotoxicity in a variety of tumor cell lines including ovarian; OV-90, OVCAR3, and breast cancer; SKOV-3. Cytotoxicity assays generated EC50 in the femtomolar range. This cytotoxicity could be modulated by varying folic acid concentrations in the assay medium. T-cell activation was confirmed by appearance of activation markers on the cell surface and secretion of pro-inflammatory cytokines after treatment of tumor cells in combination with human PBMC's. T cell activation and subsequent cytokine release is dependent on simultaneous binding of tumor and T cell to anti-CD3-Folate. In a xenograft mouse model of ovarian cancer, anti-CD3-folate significantly inhibited tumor growth, and increased life span (ILS)of 30% and 50% for SKOV-3 and OV-90, respectively when compared to control treated animals. These data suggest that anti-CD3-folate bispecifc FAb- mediated T cell engagement could be a powerful tool for immune-ablation of ovarian cancer.

Citation Format: Jinming Xia, Kristine deDios, Evelyn Rodrigo, Robin Humphreys, Alan Wahl, Marco Gymnopoulos. Bispecific anti-CD3-folate for the treatment of ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A58.