bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P6-10-19: Clinicopathologic features of breast cancers that develop in women with previous benign breast disease
Authors: Visscher DW , Frost MH , Hartmanan LC , Frank RD , Vierkant RA , McCullough AE , Winham SJ , Vachon C , Ghosh K , Brandt KR , Farrell AM , Tarabishy Y , Hieken TJ , Haddad TC , Kraft RA , Radisky DC , Degnim AC
Published: May 2016

Background

Women with benign breast disease (BBD) have an increased risk for breast cancer (BC). Almost 30% of all BCs develop in women with prior BBD. Information about the features of the expected BCs after BBD would enable individualized surveillance and prevention strategies for these women. We sought to characterize BCs developing in a large cohort of women with BBD.

Methods

Our cohort includes 13,485 women who underwent breast biopsy for mammographic or palpable concern between 1967-2001. Biopsy slides were reviewed and classified as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH). BCs were identified by follow-up questionnaires, medical records, and Tumor Registry data. BC tissues were obtained and reviewed.

Results

With a median follow-up of 15.8 years, 1273 women developed BC. Most BCs were invasive (81%), among which 61% were ductal, 13% mixed ductal/lobular, and 14% lobular. Two thirds were intermediate or high-grade, and 29% were node positive. Cancer characteristics were similar across the three histologic categories of BBD, with similar frequency of DCIS and invasive disease, tumor size, time to invasive BC, histologic type of BC, nodal positivity and HER2 positivity. Women with AH had a higher frequency of ER+ BC (91%) vs women with PD (80%) or NP (85%), p=0.02.

Conclusion

A substantial proportion of all BCs develop in women with prior BBD. We show that the majority of BCs after BBD are invasive tumors of ductal type, with a substantial proportion node positive. 84% of cancers were ER-positive. Chemoprevention should be strongly encouraged in higher-risk women with BBD.

Citation Format: Visscher DW, Frost MH, Hartmanan LC, Frank RD, Vierkant RA, McCullough AE, Winham SJ, Vachon C, Ghosh K, Brandt KR, Farrell AM, Tarabishy Y, Hieken TJ, Haddad TC, Kraft RA, Radisky DC, Degnim AC. Clinicopathologic features of breast cancers that develop in women with previous benign breast disease. [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 P6-10-19.
Abstract P6-11-01: Cost-effectiveness of pertuzumab in HER2+ metastatic breast cancer
Authors: Qian Y , Durkee BY , Pollom EL , King M , Dudley SA , Shaffer JB , Chang DT , Gibbs IC , Goldhaber-Fiebert JD , Horst KC
Published: May 2016

Purpose

The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab (P) to docetaxel and trastuzumab (TH) as first-line treatment for patients with HER2 overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of the addition of pertuzumab to docetaxel and trastuzumab.

Patient and Methods

We developed a decision-analytic Markov model to evaluate the cost-effectiveness of TH with or without P in U.S. patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included: stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. One-way and multi-way deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions.

Results

Modeled median survival was 39.4 months (TH) and 56.9 months (THP). The addition of pertuzumab resulted in an additional 1.81 life years gained (0.62 QALYs) at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost-effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost-effectiveness at a willingness-to-pay of $100,000 per QALY gained.

Conclusion

The addition of pertuzumab to docetaxel and trastuzumab in patients with metastatic HER2+ breast cancer is unlikely to be cost-effective in the United States.

Citation Format: Qian Y, Durkee BY, Pollom EL, King M, Dudley SA, Shaffer JB, Chang DT, Gibbs IC, Goldhaber-Fiebert JD, Horst KC. Cost-effectiveness of pertuzumab in HER2+ metastatic 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 P6-11-01.
Abstract P6-13-12: Comparative similarity of ABP 980 and trastuzumab: Results of functional similarity and human pharmacokinetic assessment
Authors: Hanes V , Born T , Chow V , Zhang N , Howard M , Schulz A , Markus R
Published: May 2016

Background: ABP 980 is being developed as a biosimilar to trastuzumab, a monoclonal antibody (mAb) that binds human epidermal growth factor receptor 2 (HER2), resulting in proliferation inhibition (PI) and induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Biosimilar mAbs are likely to have minor differences with the reference product due to variances in expression systems, bioprocess, and purification; demonstration of analytical, pharmacologic, and pharmacokinetic (PK) similarity is the foundation for biosimilarity. Functional (PI, ADCC, and tumor xenograft models) and PK similarity between ABP 980 and EU-authorized trastuzumab reference product has been previously evaluated.

Objective: To demonstrate functional and PK similarity between ABP 980 and FDA-licensed trastuzumab reference product.

Methods: Potency of ABP 980 and FDA-licensed trastuzumab was compared by measuring PI and recombinant HER2 (rHER2) binding affinity. PI activity was evaluated using BT-474 cells. Surface plasmon resonance analysis was used to determine the equilibrium binding affinity (Kd) to rHER2. PK similarity was evaluated in a randomized, single-blind, single-dose, parallel-group study in healthy adult men. Primary endpoints were area under the serum concentration-time curve from time 0 to infinity (AUCinf) and maximum observed serum concentration (Cmax). Secondary endpoints were safety, tolerability, and immunogenicity.

Results:

ABP 980 displayed PI and rHER2 binding activities comparable to trastuzumab. The range of relative potency by PI was 82%–114% for ABP 980 and 91%–116% for trastuzumab. The Kd ranged from 75–79 pM for ABP 980 and 67–80 pM for trastuzumab. PK similarity was demonstrated for the comparison of ABP 980 with trastuzumab. The geometric mean (GM) ratios for Cmax and AUCinf were 1.04 (90% CI, 0.995–1.079) and 1.06 (90% CI, 0.997–1.117). Both CIs fell within the standard prespecified bioequivalence criteria of 0.80–1.25. After 6 mg/kg intravenous infusion, the GM of Cmax and AUCinf were 135.90 µg/mL and 34061.43µg·h/mL for ABP 980 and 131.19µg/mL and 32271.67µg·h/mL for trastuzumab. The incidence of treatment-emergent adverse events (TEAEs) was comparable between treatment groups. TEAEs occurred in 84% subjects receiving ABP 980 and 75% of subjects receiving trastuzumab; no anti-drug antibodies were detected.

Conclusions: ABP 980 has been shown to be similar to FDA-licensed trastuzumab in functional tests and binding affinity to antigen, as well as in a phase 1 human PK study.

Citation Format: Hanes V, Born T, Chow V, Zhang N, Howard M, Schulz A, Markus R. Comparative similarity of ABP 980 and trastuzumab: Results of functional similarity and human pharmacokinetic assessment. [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 P6-13-12.
Abstract P6-19-03: Overexpression of FOXM1 is a potential prognostic marker in male breast cancer
Authors: Rahal K , Abdeljaoued S , Bettaieb I , Bouzaiene H , Adouni O , Miladi S , Goucha A , Bouaziz H , Makhlouf R , Hechiche M , Benna F , Boussen H , El May A , Gamoudi A
Published: May 2016

Background

The Forkhead box M1 (FOXM1) transcription factor is known to play an important role in the development and progression of many cancer types including breast cancer. The important role of FOXM1 in cancer affirms its significance for clinical use and therapeutic intervention. Elevated expression of FOXM1 in female breast cancer correlates with undifferentiated tumor phenotype and negative clinical outcome. However, whether FOXM1 has any indication for prognosis in male breast cancer (MBC) patients is still unknown. The purpose of this study was to examine the expression levels of FOXM1 in MBC and to identify the relationship between FOXM1 expression and patient survival.

Methodsl

Immunohistochemical analysis for FOXM1 was performed in a total of 80 male breast cancer specimens, all with linked clinical outcome data. Kaplan-Meier method and Cox proportional hazards analysis were used to relate FOXM1 expression to clinicopathological variables and overall survival (OS).

Results

We observed high expression of the FOXM1 protein in 39 % of MBC samples (31/80). FOXM1 overexpression was significantly associated with higher histological grade (p=0.05), lymph node metastasis (p=0.04), tumor size (p=0.05), and estrogen receptor expression (p=0.04). Patients with FOXM1 expression had a significantly poorer overall survival than those without FOXM1 expression (p=0.02). Multivariate analyses indicated that FOXM1 positivity was an independent prognostic factor for OS (p=0.03).

Conclusion

These results show that FOXM1 may represent a novel MBC marker with prognostic significance that could be included into the limited marker panels for MBC.

Citation Format: Rahal K, Abdeljaoued S, Bettaieb I, Bouzaiene H, Adouni O, Miladi S, Goucha A, Bouaziz H, Makhlouf R, Hechiche M, Benna F, Boussen H, El May A, Gamoudi A. Overexpression of FOXM1 is a potential prognostic marker in male 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 P6-19-03.
Abstract PD3-04: PAK-1 amplified breast cancer cell lines are preferentially sensitive to PAK inhibition with G-5555
Authors: Ong CC , Blackwood E , Jakubiak D , Daemen A , Ramaswamy S , Heise C , Schmidt M , Sanders L , Wilson TR , Huw L , Ndubaku C , Rudolph J , Hoeflich KP , Friedman L , O'Brien T
Published: May 2016

The small GTP-binding proteins Rac1 and Cdc42 stimulate activity of the serine/threonine kinase p21-activated kinase-1 (PAK-1) to drive growth factor signaling networks and Ras-driven tumorigenesis. Genomic amplification and over-expression of PAK1 are prevalent in luminal breast cancer and correlate with poor clinical outcome. Here we use a novel and selective small molecule inhibitor, G-5555, of the group I PAKs (PAK1, 2, and 3) to evaluate the importance of PAK1 in promoting growth of PAK1 amplified breast cancer cells. Cell lines with amplification of PAK1 were found to be more sensitive to PAK1 inhibition than non-amplified cell lines. Additionally, reverse phase protein array (RPPA) was used to assess the effects of PAK1 inhibition on a wide range of signaling pathways in both amplified and non-amplified cell lines. Reduced levels of phosphorylation of MEK S298 was observed in all cell lines exposed to G-5555 irrespective of amplification status, consistent with PAK1 inhibition in these cell lines. However, modulation of this downstream PAK1 substrate did not correlate with inhibition of cell proliferation or induction of cell death. Cell lines that showed inhibition of proliferation in response to G-5555 also showed enhanced levels of cell death along with apoptosis. Moreover, G-5555 reduced tumor growth in the PAK1 amplified MDA-MB-175 xenograft tumor model. Finally, we compared the in vitro activity of G-5555 with palbociclib, a recently approved inhibitor of the cyclin-dependent kinases CDK4 and CDK6, in PAK1 amplified luminal breast cancer cell lines. Our data supports PAK1 as an attractive target in PAK1 amplified cells and tumors and suggests that inhibiting PAK1 rather than CDK4/6 in this context may be a more attractive therapeutic strategy.

Citation Format: Ong CC, Blackwood E, Jakubiak D, Daemen A, Ramaswamy S, Heise C, Schmidt M, Sanders L, Wilson TR, Huw L, Ndubaku C, Rudolph J, Hoeflich KP, Friedman L, O'Brien T. PAK-1 amplified breast cancer cell lines are preferentially sensitive to PAK inhibition with G-5555. [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 PD3-04.
Abstract PD4-04: Psychosocial factors related to interruptions in adjuvant hormonal therapy among women with breast cancer: The breast cancer quality of care study (BQUAL)
Authors: Hershman DL , Kushi LH , Hillyer GC , Coromilis E , Buono D , Lamerato LE , Bovbjerg DH , Mandelblatt8 JS , Tsai W-Y , Jacobson JS , Wright JD , Neugut AI
Published: May 2016

Background. Adjuvant hormonal therapy (HT) for hormone-sensitive breast cancer decreases risk of breast cancer recurrence and improves survival. However, some women are non-adherent to this life-saving treatment.

Methods. In a cohort of women recruited at diagnosis of breast cancer in an integrated healthcare system, we investigated factors related to HT interruption (≥90 day gap). Serial interviews were conducted at baseline and during treatment to examine psychological factors as well as sociodemographic factors, tumor characteristics, and treatment factors. A series of multivariate models assessed potential predictors of HT interruptions.

Results. Of the 569 women in our cohort who initiated HT, 137 (24%) interrupted it, including 18 (3%) who did so prior to the first follow-up interview. In a multivariate analysis of clinical and demographic factors, only household income remained associated with HT interruption (OR 0.42, 95%CI 0.24-0.76). At first follow-up, after controlling for income, race and age, lower scores on all quality of life subscales, lower scores on global treatment satisfaction, and poorer scores on the intrusive and avoidant thought subscales of the Impact of Events scale were associated with higher odds of HT interruptions (P<0.001 for all predictors). Scores on social support and on interpersonal processes of care measures were not associated with HT interruptions. However, a higher score on the single question "How often did your doctor speak too fast?" was associated with higher risk of HT interruptions (OR 1.32, p=0.02).

Conclusions: Patients under greater duress and those with lower physical, functional, emotional or social quality of life appeared to be at the highest risk of HT interruption and thus received poorer quality care. A better understanding of psychological factors that can result in poor quality care may pave the way to targeted interventions to improve adherence.

Citation Format: Hershman DL, Kushi LH, Hillyer GC, Coromilis E, Buono D, Lamerato LE, Bovbjerg DH, Mandelblatt8 JS, Tsai W-Y, Jacobson JS, Wright JD, Neugut AI. Psychosocial factors related to interruptions in adjuvant hormonal therapy among women with breast cancer: The breast cancer quality of care study (BQUAL). [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 PD4-04.
Abstract A01: The efficacy of a diabetic registry to improve survival rates in under-resourced environments
Authors: Anderson Tania , Maynor Alexis , beech Derrick , Alema-Mensah Ernest
Published: May 2016

Purpose: African Americans are disproportionately affected by diabetes and the associated complications of metabolic syndrome compared to Caucasians. Diabetes is the seventh leading cause of death in the United States thus contributing to over 300,000 deaths in the U.S. annually. Thirteen percent of those diagnosed are African Americans. Factors associated with optimally managing diabetes include periodic measures of Fasting Blood Glucose (FBG), Hemoglobin A1c (HgbA1c) and Body Mass Index (BMI). We hypothesize that a Diabetes/ Metabolic Disease Registry is an effective way to assess the management of diabetes and will assist in controlling and ultimately reducing morbidity and mortality rates, particularly in underserved communities.

Methods: A diabetes metabolic disease registry was created based on best-practice clinical parameters. Demographic factors, co-morbidities and overall health maintenance were assessed. The instrument was evaluated using 52 de-identified patients' information from local Atlanta hospitals. The registry consisted of a comprehensive questionnaire with content pertinent to the diagnosis and management of diabetes such as BMI, HgbA1c and FBG. After inputting data, Statistical Analysis Software (SAS) was used for analysis. Lastly we evaluated the data input devices (smartphone versus computer) for ease and efficiency.

Results: In this study, the mean age of the patients was 59 years of age. Eighty-eight percent were female. Over 60% of the patients were classified as obese or morbidly obese. Greater than 70% had persistently elevated levels of HgbA1C and over 65% had mildly or significantly elevated levels of FBG. Cholesterol and LDL levels were normal for about 80% of patients which indicates that those factors are not pertinent to managing diabetes.

Conclusion: A Metabolic Disease Registry is an effective way to analyze diabetes management in underserved communities. Data was accurately entered at the exact same rate for both devices suggesting that both means of data entry (computers and smartphones) are equally as efficient. The elevated levels of HgbA1c and FGB in the majority of patients indicate that the serum glucose was not being controlled effectively, in spite of the fact that the majority of patients were under long-term care of a physician and had well defined care plans. We hope that this study will assist in controlling diabetes and lower the rates among those in underserved areas.

Citation Format: Tania Anderson, Alexis Maynor, Derrick beech, Ernest Alema-Mensah. The efficacy of a diabetic registry to improve survival rates in under-resourced environments. [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 A01.
Abstract A05: Biological factors associated with cancer health disparity - a high-throughput approach using big data
Authors: Yu Kaixian , Xu Yun , Tang Ke , Steppi Albert , Zhang Jinfeng
Published: May 2016

The accumulation of public available high-throughput experimental data has made analyzing the data a bottleneck in scientific discovery. In this study, we explore a computational, high-throughput approach for identifying biological factors associated with cancer health disparity using the data available at the Cancer Genome Atlas (TCGA). We developed an integrative genomic analysis (IGA) tool, which performs multiple analysis tasks, including gene/protein level comparison, gene set level comparison and network/pathway level comparison. Several data types can be analyzed, including RNAseq, DNA methylation, miRNAseq, and protein expressions. By varying cancer types, race groups, and data types, we are able to generate a large set of novel findings, which may shed light on the biological factors associated with cancer health disparity for various cancer types and race groups. Interactive reports are generated to facilitate further exploration of the biological significance of the findings. With this high-throughput approach, the bottleneck for us now shifts to publishing the results. We invite researchers in cancer health disparity community to collaborate with us to publish the findings.

Citation Format: Kaixian Yu, Yun Xu, Ke Tang, Albert Steppi, Jinfeng Zhang. Biological factors associated with cancer health disparity - a high-throughput approach using big data. [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 A05.
Abstract A18: Exploration of Florida blacks' understanding of precision medicine for cancer care and treatment
Authors: Redwine Christina L. , Odedina Folakemi , Lyon Debra , Nguyen Jennifer
Published: May 2016

Background and Objective: African-Americans in the US have the highest cancer mortality rates. Recognizing the need to address this disparity via technological and scientific innovation, In January 2015, President Obama introduced the Precision Medicine Initiative in his State of the Union Address. Allocating $215 million dollars in the 2016 budget, precision medicine should address these cancer health disparities. Yet, little is known about self-identified African-Americans/Blacks' knowledge of precision medicine.

Strategy: The objective is to understand Floridan African American men and women's knowledge of Precision Medicine and ability to successfully explain underlying concepts relative to the Precision Medicine Initiative. Using a cross-sectional design, Florida Blacks' were recruited at health forums, barbershops, salons, and churches in the state of Florida. Participants completed a self-administered survey that asked about their demographics, knowledge of precision medicine and ability to explain PMI concepts. Participants who completed the study were given either a $5 gift card of a shirt.

Results: A total of 132 participants completed the self-administered survey. Majority of the participants were female (64%) and Native U.S Blacks (85% African American of African descent). 62% were college trained and 71% were currently employed. 7% of participants had been diagnosed with cancer before and roughly 62% of them had private insurance. Well over 70% of participants have never heard of the concepts precision medicine, and pharmacogenomics. Over 50% of participants had never heard of personalized medicine, individualized medicine, and genomic sequencing. Participants were more familiar with the terms clinical trials, abnormal genes, hereditary risk, and genetic abnormality. They were also able to successfully describe the four terms that they were more familiar with. 73% participants stated that they did not know whether or not the use of precision medicine would improve cancer care and treatment.

Conclusion: The findings suggest that majority of participants are unaware of precision medicine. There was little to no understanding about the role of precision medicine in cancer care and treatment. There is a great need to educate minority populations about the Precision Medicine Initiative and identify facilitators and barriers to engagement in order to address health disparities effectively and efficiently.

Citation Format: Christina L. Redwine, Folakemi Odedina, Debra Lyon, Jennifer Nguyen. Exploration of Florida blacks' understanding of precision medicine for cancer care and treatment. [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 A18.
Abstract A27: Recruitment methods for engaging rural African American populations in community-based research
Authors: Scott Michelle , Huff Tamara , Albertie Monica , Colon-Otero Gerardo
Published: May 2016

There is a paucity of data on African Americans in community-based research secondary to difficulties in recruitment. These challenges include transportation, outreach barriers, fear and mistrust of researchers, lack of knowledge about disorder/issue under study, and lack of incentives. We hypothesized that we could improve recruitment in rural African American women by engaging community centers such as churches, community health centers, and doctor's offices.

Over a 1 month period, we sought to recruit 40 women for a community based research project with a primary outcome of increasing activity in rural African American women (45-70 years old) with knee pain. The outlets used to recruit these women included: five churches with a community liaison, many primary care physicians' offices, and a newspaper ad. In 1 month, 67 women expressed interest in our program by initiating contact. Of those 67 women, 42 were eligible and 37 were enrolled. Of the 42 eligible women, 24 were recruited from churches, 11 through word of mouth, 3 from physicians' offices, and 3 from the newspaper ad.

Lack of literature on how to recruit in rural African American communities is a significant barrier to research participation among African Americans. In this project, we provide a reproducible recruitment process for engaging rural African American women in community based research. While our primary focus was knee pain, this recruitment process can easily be translated into other areas of community based research including cancer and cardiovascular disease among others.

Citation Format: Michelle Scott, Tamara Huff, Monica Albertie, Gerardo Colon-Otero. Recruitment methods for engaging rural African American populations in community-based research. [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 A27.
Abstract A58: Interaction of diabetes and obesity in postmenopausal breast cancer risk among black women
Authors: Sanderson Maureen , Lipworth Loren , Shen-Miller David , Shrubsole Martha J. , Beeghly-Fadiel Alicia , Nechuta Sarah , Shu Xiao-ou , Zheng Wei
Published: May 2016

Purpose: Meta-analyses of the association between diabetes and postmenopausal breast cancer have been conducted primarily among white women with summary relative risks [RR] of approximately 1.15 (95% confidence interval (CI) 1.07-1.24). The only related prospective cohort study among black women reported a RR of 0.93 (95% CI 0.73-1.19). We conducted a case-control study to examine whether diabetes was associated with subsequent breast cancer among postmenopausal black women and whether obesity modified this association.

Methods: Women diagnosed with incident postmenopausal breast cancer between September 2009 and December 2012 were identified through statewide cancer registries in Georgia, South Carolina and Tennessee. One control per case, individually matched on age at enrollment, state and household income, were selected from Southern Community Cohort Study participants. Women whose breast cancer and diabetes were diagnosed within one year of each other were excluded to minimize detection bias resulting in 839 cases and 839 controls for analysis. Data on diabetes (cases n=244, controls n=336) and obesity (cases n=468, controls n=466) were obtained from baseline surveys; data on breast cancer histologic subtype (estrogen receptor (ER) positive n=556, ER negative n=216) were from cancer registry records.

Results: Using conditional logistic regression with further adjustment for educational level and health insurance coverage, there was a reduced risk of breast cancer associated with self-reported diabetes (odds ratio (OR) 0.63, 95% CI 0.49-0.80). Obesity did not significantly modify the effect of diabetes on breast cancer, but there was a stronger risk reduction among non-obese women (OR 0.51, 95% CI 0.34-0.77) than obese women (OR 0.69, 95% CI 0.50-0.94) (p for interaction=0.25). The inverse association was more pronounced for ER positive breast cancer (OR 0.51, 95% CI 0.37-0.70) than ER negative breast cancer (OR 0.84, 95% CI 0.51-1.37). However, the difference was not statistically significant.

Conclusions: In this large case-control study among black women, we found the first evidence suggesting a significant inverse association between diabetes and postmenopausal breast cancer risk. Future studies are needed to confirm our findings and to evaluate the underlying mechanisms, particularly regarding metformin use.

Citation Format: Maureen Sanderson, Loren Lipworth, David Shen-Miller, Martha J. Shrubsole, Alicia Beeghly-Fadiel, Sarah Nechuta, Xiao-ou Shu, Wei Zheng. Interaction of diabetes and obesity in postmenopausal breast cancer risk among black women. [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 A58.
Abstract A61: Deleterious consequences of BRCA1 or BRCA2 mutations via CRISPR-Cas9 in ancestrally distinct triple-negative breast cancer cell lines
Authors: Spears Marcus , Ricks-Santi Luisel , McDonald John Tyson
Published: May 2016

There is a critical need to identify additional viable treatment options for triple negative breast cancer (TNBC) that is more likely to develop in African American (AA) women who have a lower incidence of BCa, in general, but have a higher mortality from all invasive BCa subtypes compared to Caucasian (CA) women. The ground-breaking genomic editing CRISPR-Cas9 technology was used to better understand cancer driving mutations amongst two different genetic backgrounds. Using this tool, potentially deleterious mutations in the BRCA1 or BRCA2 DNA repair genes were introduced in triple negative breast cancer (TNBC) lines from African or Caucasian ancestries. The dependence of the tumor protein p53 (TP53) activity due to the R248Q mutation was also be examined by reverting that mutation to wild-type. As a positive control, we also targeted the “187delAG” mutation in the BRCA1 gene. This mutation is a two base-pair deletion (AG), causing a frameshift mutation resulting in a stop codon and premature truncation leading functional loss of BRCA1. Following successful introduction of this variant in two TNBC cell lines (AA: HCC70 & CA: HCC1143), two other variants identified previously by next generation sequencing of 32 high risk patients (young African American women with breast cancer) were also tested. To introduce the variants, guide RNA (gRNA) sequences were designed using the online CRISPR design tool (http://crispr.mit.edu). Three optimal gRNAs were chosen to limit off-target effects, mismatches close to the PAM site and minimize the distance to the target site. To ensure homologous recombination repair, template donor sequences (100bp) were designed with the target variant as well as a silent mutation site to introduce either an Hpy8I or SsiI cut site. Cells were transfected via Lipofectamine Messenger Max with the donor sequence, mRNA for the Cas9 protein and gRNA from the GeneArt CRISPR T7 Strings system. The most efficient gRNA was chosen for further optimization. Finally, the R248Q TP53 mutation in both cell lines was reverted to wild-type. The introduction of these mutations were tested for the effects on cell survival in response to ionizing radiation and bleomycin to determine the functional consequences. Future studies will introduce variants of unknown significance for functional testing to better understand potential drug targets in precision medicine.

Citation Format: Marcus Spears, Luisel Ricks-Santi, John Tyson McDonald. Deleterious consequences of BRCA1 or BRCA2 mutations via CRISPR-Cas9 in ancestrally distinct triple-negative breast cancer cell lines. [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 A61.
Abstract B07: Design and preliminary outcomes of a study to reduce cancer-associated reactive metabolite levels in breast cancer survivors – The RCAM Study
Authors: Ford Marvella E. , Turner David P. , Gregoski Mathew J. , Peterson Lindsay L. , Knight Kendrea D. , Hilton Ebony J. , Magwood Gayenell
Published: May 2016

Breast cancer (BCa) is the 2nd leading cause of cancer death in women in the US. African American (AA) women have higher BCa mortality rates and higher obesity rates compared to other women. It is well known that exercise and a healthier diet can improve prognosis among BCa survivors but little is known about their positive effects on common biological pathways involved in BCa recurrence. The RCAM Study is a 1-year study designed to identify bio-behavioral pathways that may impact BCa recurrence. The study evaluates the effect of the intervention on a novel biomarker associated with cancer recurrence advanced glycation end products (AGEs). The intervention, adapted from the highly successful Diabetes Prevention Program (DPP), consists of a 12-week physical activity and dietary counseling program. The supervised physical activity component is conducted twice a week at a local health system's cardiopulmonary rehabilitation center; the individualized dietary counseling component is conducted weekly at the health system's weight management center. The study participants consist of overweight or obese women who received surgery for invasive BCa and who are within 36 months of diagnosis. In addition, adjuvant therapy must have been received at least four weeks prior to study enrollment. To date, 10 participants have completed the 12-week intervention and will be followed for 1 year. Preliminary ELISA data from blood samples collected pre- and post-12 week intervention show significant post-intervention reductions in inflammatory biomarker levels. Commensurate decreases in body mass, resting heart rate, and blood pressure were also seen. The average pre-/post-intervention decrease in AGE levels was not as dramatic for the AA participants, most of whom were morbidly obese at enrollment, as for the European American (EA) women, most of whom were overweight at enrollment. These data demonstrate the high potential of the RCAM intervention in improving prognosis among BCa survivors and show the need to tailor the intervention to meet the specific needs of AA women.

Citation Format: Marvella E. Ford, David P. Turner, Mathew J. Gregoski, Lindsay L. Peterson, Kendrea D. Knight, Ebony J. Hilton, Gayenell Magwood. Design and preliminary outcomes of a study to reduce cancer-associated reactive metabolite levels in breast cancer survivors – The RCAM 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 B07.
Abstract B09: Fetuin-A, an emerging biomarker for breast and prostate cancer
Authors: Nangami Gladys , Ochieng Josiah , Appah Ebenezer , Lammers Philip E.
Published: May 2016

We hypothesized that fetuin-A, a liver derived glycoprotein would be a useful biomarker to follow for the progression of prostate and breast cancer particularly in African American patients. For many years, conflicting reports have appeared in the literature regarding the role of fetuin-A in the progression of a number of solid tumors. The majority of the studies have reported that the serum levels of fetuin-A drops as tumors progress, suggesting a tumor suppressive role for the protein. We on the other hand, demonstrated that it is a significant tumor growth promoter in vitro. In the recent past, a number of laboratories, including ours, have indicated that fetuin-A is actively synthesized by high grade tumors.

In the present study, we investigated the appearance of fetuin-A autoantibodies in the sera of 12 prostate and breast cancer patients, 60% of whom were African Americans. We demonstrated the presence of fetuin-A auto antibodies in all except two of the tumor serum specimens. Blood of normal tumor free individuals do not show fetuin-A autoantibodies. We also subjected tissue microarrays of prostate and breast tumors to immune-histochemical analysis of fetuin-A. Our data show a dramatic increase in the synthesis of fetuin-A in the TMA particularly in high grade tumors. Taken together, these results suggest that as tumors become more aggressive they may synthesize fetuin-A which then presents as a new antigen in the blood that provokes the synthesis of auto-antibodies, which could be a biomarker of advanced or metastatic disease. Furthermore, the study suggests that fetuin-A itself could be a significant surrogate marker of aggressive tumors of the prostate or breast particularly in African Americans.

Citation Format: Gladys Nangami, Josiah Ochieng, Ebenezer Appah, Philip E. Lammers. Fetuin-A, an emerging biomarker for breast and prostate cancer. [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 B09.
Abstract B12: Macrophage inhibitory cytokine-1 as a potential biomarker for racial disparity in prostate cancer
Authors: Karan Dev , Dubey Seema , Wick Jo , Tawfik Ossama , Sonpavde Guru , VanVeldhuizen Peter
Published: May 2016

Macrophage inhibitory cytokine-1 (MIC-1) has drawn significant attention due to its association with the development and progression of prostate cancer (PCa). Recent studies have projected MIC-1 as a potential biomarker for various disease conditions including PCa. Given evidence for more aggressive disease among African American (AA) men, we aimed to investigate if MIC-1 was differentially expressed among AA and Caucasian men. We measured serum MIC-1 levels by sandwich ELISA in samples collected during the diagnosis of PCa (pre-surgical). Our data consists of information on 40 Caucasian and 40 AA men between the ages of 43 and 75 years (Median = 60 years). Based on the analysis of log transformation of the data, significant differences among the two races were found, with AA having higher MIC-1 expression (Median 1220.4 versus 790.8, p=0.0001), Gleason scores (Median 7 versus 6, p=0.0009) and PSA (Median 6.72 versus 6.35 ng/ml, p = 0.04) than Caucasians. No differences in age or pathological stage of disease were observed between groups (p > 0.05). Higher levels of MIC-1 and Gleason scores were associated (p<0.001 and p<0.05, respectively) with older patients among Caucasians. In contrast, among AA samples, MIC-1 and Gleason scores were not differentially expressed based on age. This phenomenon was not observed when examining PSA expression levels by age among AA and Caucasians. Altogether, these observations indicate that MIC-1 may play a role in more aggressive disease among younger AA men and addition of MIC−1 may help to improve the discrimination of aggressive disease at least in AA men. Further analysis of the mechanism of activity of MIC-1 and validation in a larger dataset is required.

Citation Format: Dev Karan, Seema Dubey, Jo Wick, Ossama Tawfik, Guru Sonpavde, Peter VanVeldhuizen. Macrophage inhibitory cytokine-1 as a potential biomarker for racial disparity in prostate cancer. [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 B12.
Abstract B13: Differential expressions of stress proteins and miRNAs in circulating exosomes in prostate cancer health disparities
Authors: Khan Salma , Stiff TessaRae , Simpson Jennifer , Lynch James C. , Leaf Patrick , Gonda Amber , mirshahidi saeid , Sanchez Tino , Casiano Carlos A. , Wall Nathan R.
Published: May 2016

African American men are about 1.5 times more likely to develop prostate cancer and about 2.5 times more likely to die from prostate cancer. However, there's no known cause of increased rate of morbidity and mortality in these population. Stress is well known factor for the causation of health disparities. Stress is a known inducer of post-transcriptional modification in cellular levels. Survivin, a member of the inhibitor of apoptosis family can get alternatively spliced both transcriptionally and post-transcriptionally. We have shown that survivin and its splice variants are secreted from cells via exosomes, small membrane-bound vesicles used in cell-cell and cell-extracellular communication (1,2). MicroRNAs (miRNA) are small RNA, play regulatory role in tumor development and prognosis. Main objective of the present study is to find out differential expression patterns of stress proteins and miRNA from circulating exosomes deived from prostate cancer in African American (PCa-AA) and Caucasian (PCa-CC) patient populations. This is a novel way of establishing non-invasive early detection intervention that can be tailored to Americans of different ethnicities. In this study, exosomes are collected from sera of PCa-AA and PCa-CC using the commercially available ExoQuick kit. miRNAs are extracted from the exosomes using QIAGEN miRNA kit. Differential expressions of IAPs, wild type survivin and its splice variants are noted in the exosomes of AA-prostate cancer patients' sera compared to CC-prostate cancer sera. Differentially expressed miRNAs are identified by sequencing analysis. We find that this observation will ultimately pave the way for future studies focused on analyzing these biomarkers in larger cohorts of ethnically diverse cancer patients.

Citation Format: Salma Khan, TessaRae Stiff, Jennifer Simpson, James C. Lynch, Patrick Leaf, Amber Gonda, saeid mirshahidi, Tino Sanchez, Carlos A. Casiano, Nathan R. Wall. Differential expressions of stress proteins and miRNAs in circulating exosomes in prostate cancer health disparities. [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 B13.
Abstract B23: Neuroendocrine differentiation in prostate cancer and development
Authors: Sanders Danielle N. , Grabowska Magdalena , Matusik Robert
Published: May 2016

Introduction: It is now recognized that androgen deprivation therapy (ADT) can induce neuroendocrine (NE) differentiation (NED) in prostate cancer (PCa) as well as histologically distinct NE cancer in >25% of castrate resistant prostate cancer (CRPCa). Neuroendocrine cells, which are present but rare in the normal prostate, secrete growth factors but the mechanism of normal NED in the developing prostate is largely unknown. We hypothesize that the neuroendocrine phenotype, seen in CRPCa, recaptures events that occurs during normal prostatic development in response to the androgens. The purpose of these experiments is to determine if NED occurs in the development of the normal mouse prostate in response to androgen.

Methods: 8-10 week old male mice (n=7 per group) were castrated and 2 weeks post-castration were treated with androgens (DHT) or oil (control), and then euthanized 1, 2 or 4 hours after treatment. Prostate lobes were then dissected, analyzed by immunohistochemistry for synaptophysin, a marker of NED, and scored blindly (Table 1). Intensity and distribution were then summed and analyzed using the Mann-Whitney test.

Score Intensity Distribution

0 No expression No expression

1 Weak Antibody expression in 0-33% of epithelial cells

2 Mild Antibody expression in 33%-66% of epithelial cells

3 Strong Antibody expression in 66%- 100% of epithelial cells

Table 1: Immunohistochemistry scoring system

Results: No significant difference in synaptophysin staining was found in the epithelium between oil and DHT treated samples in the anterior, dorsal, and lateral prostate. There was a significant difference in synaptophysin staining found between oil and DHT treated samples at the 1 hour time point in the ventral prostate (p < 0.05). This difference disappeared in subsequent time points in the ventral prostate.

Conclusion: Androgens induce rapid and transient NED in the murine ventral prostate epithelium, indicated by a spike in synaptophysin at the 1 hour time point. By 2 hours, there is no significant difference in synaptophysin staining between the oil and DHT treated samples. This transient elevation in a NED marker is only observed in the ventral lobe. This indicates that CRPCa may recapture events that occur in the growth of the normal prostate.

Citation Format: Danielle N. Sanders, Magdalena Grabowska, Robert Matusik. Neuroendocrine differentiation in prostate cancer and development. [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 B23.
Abstract B67: Increasing access to cancer prevention and early detection screenings among racial/ethnic minorities: An innovative same-day result model
Authors: Brown Jameisha B.
Published: May 2016

Purpose: Cervical cancer is detected among more than 12,000 women, annually. Some age groups are affected disproportionately, at nearly 25% higher rates of new cases than other women. Following recommended pap screening guidelines, cervical cancer can essentially be eliminated. Likewise, when breast cancer is detected at earlier stages the greater the likelihood of 5-year survival, 98%. The See, Test & Treat® Houston screening model provides free breast and cervical cancer screenings with same-day results to communities identified as underserved.

Methods: Through a multidisciplinary volunteer collaboration, this novel screening model targeted medically underserved women between ages 21-65 with 1) breast and cervical cancer screenings, 2) same-day results, 3) health education counseling, 4) and the connection to follow-up care in a culturally and linguistically competent setting at no cost to the women served.

Results: Over 750 women attended the free special screening programs over a 3-year period. Of those that participated, 673 women who had never or rarely been screened received a pelvic and breast examination and a Pap test through the program. Of these women, 55 had abnormal Pap tests and 28 of these underwent same day colposcopy and 9 completed a LEEP. Seventy-six mammograms were performed. Two Breast Fine Needle Aspirations were provided on-site for women with a palpable breast mass. Four breast malignancies were detected. The population served were predominately minorities, low income, uninsured or under-insured, and between 40-49 years.

Conclusions: Findings suggest that additional dissemination of same-day screen, result and treat models are promising to reach demographics most affected by breast and cervical cancer disparities. As health seeking behavior plays a pivotal role in the outcome of any disease, including a health education component in all screening programs can continue to promote proactive preventive screening seeking behaviors and better provision of culturally-sensitive community screening programs.

Citation Format: Jameisha B. Brown. Increasing access to cancer prevention and early detection screenings among racial/ethnic minorities: An innovative same-day result model. [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 B67.