bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD2-06: Mismatch repair deficiency induces endocrine therapy resistance in breast cancer
Authors: Haricharan S , Schmelz J , Schmidt C , Singh P , Holloway K , Anurag M , Suman V , Olson JA , Hunt K , Bainbridge MN , Ellis MJ 
Published: March 2017

Abstract
Estrogen receptor positive (ER+) breast cancer accounts for the majority of breast cancers diagnosed worldwide but fortunately, outcomes are markedly improved by pharmacological interventions that interrupt ER function. Unfortunately, suppression of relapse risk from early stage disease with endocrine therapy (anti-estrogens or aromatase inhibitors) is only ∼50%, and for advanced disease, pan endocrine therapy resistance is almost inevitable. While many mechanisms for intrinsic and acquired endocrine resistance have been explored, links between defects in DNA repair, the fundamental drivers of cancer pathogenesis, and endocrine therapy resistance have been understudied. Here we link mismatch repair (MMR) deficiency to poor clinical outcomes in ER+ breast cancer using whole exome DNA sequencing data and mRNA expression analysis. We subsequently demonstrate that MMR deficiency bypasses ER dependent cell cycle regulation through disruption of Chk2/p21-mediated feedback inhibition of CDK4 in breast cancer cell lines and tumor samples, as well as through correlations with human clinical data. We also show that pharmacological targeting of CDK4 significantly inhibits growth of MMR-deficient ER+ breast cancer cells in vitro and in vivo. This mechanism provides a new explanation for why endocrine therapy resistant ER+ breast cancers can respond to CDK inhibition and suggests that primary tumors exhibiting MMR deficiency are good candidates for adjuvant CDK4 inhibitor treatment.
Citation Format: Haricharan S, Schmelz J, Schmidt C, Singh P, Holloway K, Anurag M, Suman V, Olson JA, Hunt K, Bainbridge MN, Ellis MJ. Mismatch repair deficiency induces endocrine therapy resistance in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD2-06.
Abstract PD8-01: Race and age differences in PAM50 biomarker status in the Carolina breast cancer study
Authors: Troester MA , Sun X , Allott EH , Kit C-K , Thorne L , Mathews M , Cohen SM , Geradts J , Kirk E , Li Y , Hu Z , Robinson W , Hoadley KA , Reeder-Hayes K , Earp S , Olshan AF , Carey LA , Perou CM 
Published: March 2017

Abstract
Background: African American breast cancer patients have lower relative frequency of hormone receptor (HR)-positive/HER2-negative disease and higher subtype-specific mortality. However, few population-based studies have RNA-based subtyping data, and racial differences in the biology of HR-positive/HER2-negative tumors are not well understood.
Methods: Using data and biospecimens from the Carolina Breast Cancer Study (CBCS) Phase 3 (2008-2013), we classified approximately 1,000 invasive breast cancers according to PAM50 subtype and two risk of recurrence scores (ROR-P and ROR-PT). Relative frequency of Luminal A, Luminal B, Her2-enriched, and Basal-like subtypes and ROR scores (low/medium/high) were compared by race (blacks vs. whites) and age (≤50 years vs. &gt;50 years), overall and among HR-positive/HER2-negative cases.
Results: Black women of all ages had significantly higher relative frequency of Basal-like breast cancer (36 and 31% in blacks vs. 18 and 15% in whites; younger and older, respectively) and lower frequency of Luminal A breast cancer (26 and 34% in blacks vs. 43 and 52% in whites; younger and older, respectively). Frequency of Luminal B and HER2-enriched breast cancer did not vary by race or age. Among clinically HR-positive, HER2-negative cases, Luminal A subtype comprised only half of the cases among black women, and was significantly less common than among white women (51% vs 60% in whites, p&lt;0.05). Black women with HR-positive/HER2-negative disease also had significantly higher ROR scores (ROR-P medium or high 82% vs. 66% in whites, p=0.01; ROR-PT medium or high 85% vs. 69% in whites, p&lt;0.01).
Conclusions: Multi-gene assays highlight disparities in frequency of aggressive, poorer prognosis tumor subtypes and implicate differences in tumor biology as an important contributor to mortality disparities among HR-positive/HER2-negative patients.
Citation Format: Troester MA, Sun X, Allott EH, Kit C-K, Thorne L, Mathews M, Cohen SM, Geradts J, Kirk E, Li Y, Hu Z, Robinson W, Hoadley KA, Reeder-Hayes K, Earp S, Olshan AF, Carey LA, Perou CM. Race and age differences in PAM50 biomarker status in the Carolina breast cancer study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD8-01.
Abstract PL3: Global cost of cancer care
Authors: Bach PB 
Published: March 2017

Abstract
According to a 2014 IMS health report, cancer drugs represent 26% of specialty drug spending, more than $32B in the US in 2014, and specialty drug spending is growing faster than any other sector of healthcare. Unsurprisingly, cancer drugs are the largest sub-segment. These price rises are not just an economic curiosity. Because of the structure of many insurance products, the co-insurance on these expensive drugs is crippling, impacting access on a large scale. A recent study reported that more than 10% of Medicare beneficiaries with a cancer diagnosis face out of pocket expenses exceeding their incomes. In a nationally representative survey conducted in 2006, twenty-five percent of patients reported exhausting all or most of their savings. In a recent analysis of discontinuation rates among patients taking Gleevec and other highly effective drugs for Chronic Myeloid Leukemia, patients with high copayments were 42% more likely to be nonadherent.
Dr. Bach has researched this problem with a data-driven set of related projects that aim to achieve substantive change to pricing of and access to specialty drugs, beginning with cancer drugs because of established expertise, but expanding to other analogous areas rapidly.
In 2009, Dr. Bach's team began tracking the launch prices of new cancer drugs, a project which has shown a 100-fold increase in introductory cancer drug prices, after adjusting for inflation. A follow-on study found that the increase in price is not accompanied in an increase in clinical value, with the cost of a year of life increasing by $8,500 a year.
In 2012, on behalf of Memorial Sloan Kettering Cancer Center, Dr. Bach publicly rejected the pricing of the cancer drug, Zaltrap, by announcing the hospital's position in the New York Times. In response, the company lowered its price by 50%, proving that the price is not tied to any specific metric (i.e. R&D costs), but is rather determined by what the market can bear.
Dr. Bach launched a project in 2015 called the DrugAbacus (drugabacus.org), an interactive web based tool that allows users to manipulate various metrics to determine the ‘value’ of cancer drugs. DrugAbacus shifted the conversation of value-based pricing from one of theory to one more focused on implementation, and has been cited as a source of pricing for both CVS and Express Scripts. The Zaltrap stance, the DrugAbacus, and much of his work has made MSKCC a leader in using evidence to shift the discussion on drug pricing, a consistent theme of which has been that the price a manufacturer sets is a product of the marketplace, not a product of the costs of their business or something else structural.
Citation Format: Bach PB. Global cost of cancer care [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PL3.
Abstract A06: All Nations Breath of Life: A culturally tailored smoking cessation program for heterogeneous urban American Indian communities
Authors: Gunville Jordyn , Goeckenr Ryan , Hale Jason , Smith T Edward , Nazir Niaman , Daley Sean , Choi Won , Daley Christine M. 
Published: March 2017

Abstract
Prevalence of cigarette smoking is highest among American Indians, yet few culturally appropriate smoking cessation programs have yet been developed and tested for multi-tribal American Indian adult populations. This study tested for effectiveness the All Nations Breath of Life culturally tailored smoking cessation program in multi-tribal urban and suburban American Indian communities in 7 locations across 5 states (N=312).
This single-arm implementation effectiveness study used community-based participatory research to conduct a 12-week intervention. Participants were followed through month 6 in person and month 12 via telephone. The primary outcome was continuous abstinence from recreational cigarette smoking at 6 months post-baseline, verified through voluntary provision of salivary cotinine levels.
At program completion, 53.3% of program completers remained abstinent; using an intent-to-treat analysis labeling those lost to follow-up as smokers resulted in a 41.4% quit rate. At 6 months post-baseline, 31.1% of retained participants quit smoking (p&lt;0.0001 compared to the highest quit rates among multi-tribal populations reported in the literature, 7%); final quit rate was 22.1% using an intent-to-treat analysis (p=0.002). Retention rate at endpoint was 71.2%. 12-month follow-up was attempted with all participants and had a retention rate of 49.0%. Of those participants reached, 34.0% were smoke-free; using an intent-to-treat analysis, the quit rate at 12 months post-baseline was 16.7%.
All Nations Breath of Life is an effective smoking cessation program for multi-tribal urban American Indian communities. It can be successfully implemented in a variety of urban settings.
Citation Format: Jordyn Gunville, Ryan Goeckenr, Jason Hale, T Edward Smith, Niaman Nazir, Sean Daley, Won Choi, Christine M. Daley. All Nations Breath of Life: A culturally tailored smoking cessation program for heterogeneous urban American Indian communities. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A06.
Abstract A37: Outcomes of a Randomized Community Trial to Increase Pap Testing among Pacific Islanders in Southern California
Authors: Tanjasiri Sora Park , Weiss Jie W. , Mouttapa Michele , Santos Lola Sablan 
Published: March 2017

Abstract
Background: Pap tests comprise an essential cervical cancer prevention and detection method for women in the U.S. Unfortunately, the Pap test remains significantly underutilized among many ethnic/racial groups, particularly Pacific Islanders (PIs) who have low rates of Pap testing and high rates of cervical cancer incidence and mortality.
Methods: A randomized community trial tested the efficacy of a social support-informed culturally developed intervention on increasing Pap testing among Chamorro, Samoan and Tongan women in Southern California. Using community-based participatory research (CBPR), Pacific Islander women and their husbands/partners were recruited from social organizations (churches and clans) that had been randomly assigned to receive the intervention or control education. Three waves (pretest, posttest and 6-month follow-up) of data collection included demographics, cervical cancer beliefs, social support between women and their husbands/partners, and Pap test attitudes and behaviors.
Results: CBPR recruitment resulted in a total of 81 social organizations recruited that included n=575 Pacific Islander women and n=461 husbands/partners. Significant differences between groups at baseline included acculturation and health insurance coverage. Six month follow-up found that all women from baseline significantly increased knowledge and decreased fatalistic attitudes towards Pap testing. Women who were not adherent to Pap test guidelines in the intervention group had significantly higher rates of Pap testing compared to controls at six month follow-up. No differences were found in either women's perceived social support nor men's provision of social support for Pap testing.
Conclusion: CBPR-informed behavioral interventions can increase cervical cancer screening in Pacific Islander women. Although social support did not mediate the relationship between women's knowledge and behavior, it did inform the development of a culturally tailored intervention for Chamorro, Samoan and Tongan women. Future studies can build upon these results by addressing other early detection (e.g., mammograms, colorectal exams, etc) and prevention (e.g., HPV vaccination) in these and other disparity populations.
Citation Format: Sora Park Tanjasiri, Jie W. Weiss, Michele Mouttapa, Lola Sablan Santos. Outcomes of a Randomized Community Trial to Increase Pap Testing among Pacific Islanders in Southern California. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A37.
Abstract B47: Combating cancer with combination therapy in underserved populations
Authors: Homayouni Tina , Mokhtari Reza Bayat , Tyker Albina , Kazemi Parandis , Morgatskaya Zhenya , Baluch Narges , Dhalla Sara , Rekhi Shreya , Kumar Sushil , Yeger Herman 
Published: March 2017

Abstract
Combination therapy is an emerging treatment modality that combines two or more agents to produce a therapeutic effect. The combined use of therapeutic agents enhance efficacy compared to the monotherapy approach because it characteristically targets main key pathways with a synergistic or an additive effect. This approach potentially reduces drug-resistance, while simultaneously producing therapeutic anti-cancer benefits, such as the potential in reducing tumor growth and metastasis, arresting the cell cycle, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rate for most cancers are still quite low, and the process of developing a new anti-cancer drug is long and extremely time consuming. Therefore, new strategies that target the survival pathways while providing efficient and effective results, as well as affordability, are being considered.
One such approach incorporates the testing of therapeutic agents initially used for the treatment of different diseases on cancer. This approach is effective primarily when the FDA approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA approved and requires less funding to research, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy and reduces the price of treatment, benefiting the “medically underserved”. In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics have shown promising results in mitigating tumor size and volume.
Note: This abstract was not presented at the conference.
Citation Format: Tina Homayouni, Reza Bayat Mokhtari, Albina Tyker, Parandis Kazemi, Zhenya Morgatskaya, Narges Baluch, Sara Dhalla, Shreya Rekhi, Sushil Kumar, Herman Yeger. Combating cancer with combination therapy in underserved populations. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B47.
Abstract C02: Electronic personal health records, minorities and prevention
Authors: Raska Paola , Schneider Katherine , Zivoder Jordan , Steele Scott , Abraham Jame 
Published: March 2017

Abstract
Introduction:
Cancer outcome disparities are in large part attributable to impediments to access to care for minority populations and individuals of lower socio-economic status. The use of electronic personal health records (ePHR) such as myChart, which allow patients to directly interact with their health record and their healthcare providers, has been drastically increasing with cancer patients overall but disproportionately less so in the underserved. We need to better understand the factors that underlie disparities in usage of ePHR, particularly for prevention, in order to be better able to leverage on this technology to improve access to care.
Methods:
In 2012 Cleveland Clinic implemented an opt out program where every patient is given a myChart activation code at check in. This has resulted in close to a million “newly active” patients and almost half a million activated MyChart users. All patients with an email address on file were invited to participate in a survey inquiring about patient knowledge, use and preferences for myChart. We used logistic regression to test for differences across ethnicity after controlling for factors that confound factors such as age and illness.
Results:
A total of 18,599 369 myChart users responded to the survey. 633 (3%) responders self-identified as Hispanic (His) and 1265 (7%) as African American (AA). Both His and AA tended to be younger and healthier (less chronic conditions) than non-Hispanic White (WHI) responders (AA OR=1.4, p = 0.001, His OR 2.0, p = 0.001). Despite this His and AA have higher frequencies of visits to their PCP and to the ER after controlling for chronic conditions and age. Although younger WHI responders were more likely to say that they would use myChart more if they visited their PCP more, this was not the case for His and AA. Instead we find that His and AA are more likely to say that they do not discuss preventative measures with their PCP (AA OR =1.3, p=0.01, His OR = 1.5, p = 0.002)
Conclusion: Our results suggest that adding functionality to ePHR that will more actively promote discussion and planning of prevention between primary care providers and His and AA may be a way to improve the impact of this technology on how minorities engage with prevention.
Citation Format: Paola Raska, Katherine Schneider, Jordan Zivoder, Scott Steele, Jame Abraham. Electronic personal health records, minorities and prevention. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C02.
Abstract C32: MicroRNA mediated megative regulation of caveolin 1 as a biological mechanism driving breast cancer disparities
Authors: Turner David P. , King Brooke , Guo Qi , Blake Bobbie , Nogueira Lourdes M. , larue amanda c. , salley judith d. , ford marvella e. , evans-knowell ashley , Findlay Victoria J. 
Published: March 2017

Abstract
In South Carolina, mortality differences between African American (AA) and non-Hispanic white (NHW) women breast cancer patients are amongst the highest in the country. Evidence suggests that the observed racial disparity exists independent of socioeconomic and standard of care issues, suggesting a potential biological factor may be involved. The loss of Caveolin-1 (Cav1) in the tumor stromal compartment has emerged as a novel biomarker for predicting poor clinical outcome in all of the most common subtypes of breast cancer, however the mechanism of Cav1 loss is unknown. We identified miR-510 as a novel oncomir and propose that its elevated expression in breast tumors results in stromal Cav1 loss and a subsequent worse outcome. In this study we used luciferase, western blot and quantitative PCR analysis to study Caveolin-1 as a direct target of miR-510. We used a co-culture system to assess crosstalk between epithelial and stromal compartments in vitro and a mouse model to assess this in vivo. Our research shows that Cav1 is a direct target of miR-510 and that overexpression of miR-510 leads to downregulation of Cav1 protein expression, specifically in the stromal compartment. This may be racially significant as our studies also show that miR-510 levels are elevated and Cav1 levels are reduced in AA breast cancer patients compared to their NHW counterparts. Data from our in vivo studies shows that cancer-associated fibroblasts (CAFs) isolated from miR-510 expressing epithelial derived tumors lead to more aggressive tumor growth when co-injected with breast tumor epithelial cells when compared to scrambled control CAF co-injections and breast tumor epithelial cells alone. Our results suggest that elevated miR-510 expression in breast epithelial cells leads to stromal Cav1 loss and is a mechanism driving racial disparity in breast cancer.
Citation Format: David P. Turner, Brooke King, Qi Guo, Bobbie Blake, Lourdes M. Nogueira, amanda c. larue, judith d. salley, marvella e. ford, ashley evans-knowell, Victoria J. Findlay. MicroRNA mediated megative regulation of caveolin 1 as a biological mechanism driving breast cancer disparities. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C32.