bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-05-01: Low BRCA2 levels cause epigenetic activation of growth adaptive pathways without inducing recurrent genomic mutations
Authors: Gruber JJ , Snyder M 
Published: March 2017

Abstract
The development of therapeutics to prevent cancer onset is hindered by a lack of robust cell systems to study the earliest steps of malignant transformation. Significant barriers to studying cancer-initiating events include intrinsic cellular pathways to prevent cell proliferation in the setting of activating oncogenes or genomic instability. To circumvent this limitation, we studied in vitro transient depletion of breast cancer tumor suppressor genes followed by selective growth conditions to enrich for de novo mutations or stable epigenetic alterations that can confer a growth advantage to non-transformed breast epithelial cells. We report that transient BRCA2 depletion, but not depletion of other breast cancer genes, leads to a selective growth advantage in EGF-free media. This is due to a failure of BRCA2 inactivated cells to enact a mesenchymal-to-epithelial transition upon withdrawal of EGF. Genomic profiling and biochemical approaches indicate that transient loss of BRCA2 induces chromatin remodeling in concert with NF-κB signaling and histone H2B deacetylation to repress genes associated with the epithelial state. Notably, this process did not appear to require recurrent driver mutations, nor DNA methylation changes, but was dependent on ATR signaling. Overall, our work suggests that transiently low BRCA2 levels are sufficient to induce aberrant cell proliferation under certain conditions and that targeting epigenetic modifiers may be an approach to prevent BRCA2-induced malignancy.
Citation Format: Gruber JJ, Snyder M. Low BRCA2 levels cause epigenetic activation of growth adaptive pathways without inducing recurrent genomic mutations [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 P6-05-01.
Abstract P6-07-18: A pilot study of the impact of a single dose of zolendronic acid on biomarkers in breast cancer
Authors: Cho M , Gong J , Chen S , Yu H , Wong L , Kruper L , Mortimer J 
Published: March 2017

Abstract
Backgrounds: In randomized trials for early stage breast cancer, patients who received adjuvant zolendronic acid (ZA) had superior disease-free survival and greater tumor shrinkage. Preclinical data suggest that ZA has anti-cancer properties by modulating angiogenesis and tumor immune environment. This is the pilot study to assess changes in tumor biomarkers and immunological function in response to a single dose of ZA in paired tumor specimens (from core biopsy and definitive surgery).
Methods: Postmenopausal women with early stage invasive ductal breast carcinoma who have estrogen receptor and/or progesterone receptor positive tumor for which a lumpectomy or mastectomy was planned prior to systemic therapy were enrolled. A single dose of ZA 4mg IV was given 10-14 days prior to their planned definitive surgery. 14 biomarkers in tumor tissue was assayed; 10 by gene microarray (VEGF, IL1β, IL-6, MMP-1, MMP-2, MMP-9, TGF, Interferon α and STAT3)) and 4 by RT-PCR(P13K, PTEN, IGF-1-R, EGFR. Patient blood samples were drawn at baseline, at 48-72hrs after the single dose of ZA and at the time of surgery and assayed for cytokines and chemokines by using 30-plex Luminex panels.
Results: Eight patients were enrolled in the study (median age 65 and range (57-75); 4 caucatians, 2 hispanic and 1 asian; 6 stage I, 1 stage II and 1 stage III). 30-plex luminex assays showed MIG, IP-10 and IL-12 were found to increase in Day 1-3 of ZA therapy from baseline and normalized by Day 10-24. MCP-1, IL2R, MIP-1b and Eotaxin were found to have changes in Day 1-3 from baseline and mix outcome by Day 10-24. EGF, G-CSF, HGF, IFN-alpha and IFN-gamma and RANTES showed no clear pattern among eight patients. Tumor markers and proteomics from pair tumor samples will be presented.
Conclusions: Changes in multiple tumor biomarkers and immunological markers, MIG, IP-10, IL-12, MCP-1, IL2R, MIP-1b, Eotaxin, IFN-alpha and IFN-gamma are seen within 2 weeks of a single dose of ZA.
Citation Format: Cho M, Gong J, Chen S, Yu H, Wong L, Kruper L, Mortimer J. A pilot study of the impact of a single dose of zolendronic acid on biomarkers 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 P6-07-18.
Abstract P6-07-31: Molecular mechanism of alcohol-associated breast cancer
Authors: Zhong S , Zhang Y , Lei J , Li W , Wu Z , Shi G 
Published: March 2017

Abstract
Epidemiological studies have indicated that alcohol consumption is an established risk factor for breast cancer. The association of alcohol consumption and breast cancer is more pronounced in ER+ cases than in ER- cases. However, this molecular mechanism remains to be determined. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, increasing translational capacity to promote cell transformation and tumor formation. Our results reveal that alcohol increases Pol III gene transcription in both normal and cancer breast cell lines. The induction of Pol III genes by alcohol in ER+ breast cancer cells is significantly higher than in ER- normal breast cells and ER- breast cancer cells. E2 causes slight increase in Pol III gene transcription. The addition of ethanol to this system produces a marked increase. Alcohol increases ERa expression to enhance the cellular levels of Brf1 protein and mRNA. In addition, ethanol markedly stimulates phosphorylation of JNK1. Inhibition of JNK1 decreases ERE-Luc reporter activity and represses expression of ERa, Brf1 and Pol III genes. Reduction of ERa by its siRNA represses Brf1 and Pol III gene transcription. Ethanol with E2 produces larger and more numerous colonies. Repression of ERa or Brf1 inhibits alcohol-induced cell transformation. More interestingly, human biopsies studies show that Brf1 expression is significantly increased in nuclei of breast cancer cells, compared to tissue adjacent to the carcinoma. Together, these results support the idea that alcohol increases ERa expression through JNK1 pathway to elevate Brf1 expression and Pol III gene transcription, leading to greater phenotypic changes. ERa mediates Pol III gene transcription through Brf1, suggesting that ERa play a critical role in alcohol-induced deregulation of Pol III genes in ER+ breast cancer development.
*: The project is supported by NIAAA/NIH grants: AA017288, AA021114 and AA02324 to S Zhong.
Citation Format: Zhong S, Zhang Y, Lei J, Li W, Wu Z, Shi G. Molecular mechanism of alcohol-associated 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 P6-07-31.
Abstract P6-09-55: “Quality, not quantity”: 10X hot-spot (HS) analysis of lymphocyte markers (CD3, CD8, CD4, CD20) in tumor-infiltrating lymphocytes (TILs) is superior to whole tumor (WT) analysis in triple-negative breast cancer (TNBC)
Authors: Cui X , McIntire PJ , Ginter PS , Irshaid L , Chen Z , Shin SJ 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P6-16-03: Phase 2 trial of everolimus and/or trastuzumab in hormone refractory, hormone receptor (HR)-positive, HER2-normal metastatic breast cancer (MBC)
Authors: Paplomata E , Gogineni K , Meisel J , Santa-Maria C , Yuan L , Kramer J , Bill Li X , Zelnak A , Pakkala S , Kaklamani V , O'Regan R 
Published: March 2017

Abstract
Background: Increased signaling through growth factor pathways including PI3K/Akt/mTOR and HER2 have been implicated in hormone resistance. Everolimus (EVE) improves outcomes when added to endocrine therapy for patients with HR-positive MBC. This study evaluated the efficacy of everolimus (EVE) and trastuzumab (TRAS) in hormone refractory HER2-normal metastatic breast cancer.
Methods: Eligible patients had HR-positive, HER2/neu-negative (IHC +1 or +2, HER2-non-amplified) MBC that had progressed within 6 months of the most recent endocrine therapy. Patients continued on the most recent endocrine therapy they received and were randomized to receive EVE 10 mg oral daily or TRAS IV (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks). At progression, the other agent was added (TRAS in the EVE arm and EVE in the TRAS arm). Patients were followed until disease progression or death.
Results: 54 eligible patients were included in the analysis, and were randomized to EVE (n=30) or TRAS (n=24). 33% of patients were on fulvestrant, 31% exemestane, 22% tamoxifen and 7% letrozole, which were continued. The median PFS was 5.7 months for EVE vs. 2 months for TRAS until first progression or death with hazard ratio of 0.45 (95% CI 0.25-0.81, p=0.008). Among 48 patients who had disease progression, EVE was added to 16 patients who were originally treated by TRAS, and TRAS was added to 12 patients who were originally treated by EVE; the median time to the second progression was 6.3 months for the arm where EVE was added vs. 3.1 months in the arm where TRAS was added. Three patients were taken off study due to decrease in ejection fraction.
Conclusions: This trial demonstrates the efficacy of EVE alone or in combination with TRAS in patients with hormone refractory HR-positive, HER2-negative metastatic breast cancer, who remained on the endocrine therapy they had experienced disease progression on. This suggests that mTOR inhibition has the potential of restoring sensitivity to endocrine therapy and potentially allows the re-use of endocrine agents. Updated results and correlative studies will be presented. Clinical trial information: NCT00912340.
Citation Format: Paplomata E, Gogineni K, Meisel J, Santa-Maria C, Yuan L, Kramer J, Bill Li X, Zelnak A, Pakkala S, Kaklamani V, O'Regan R. Phase 2 trial of everolimus and/or trastuzumab in hormone refractory, hormone receptor (HR)-positive, HER2-normal metastatic breast cancer (MBC) [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 P6-16-03.
Abstract PL2: Cell free plasma tumor DNA in breast oncology
Authors: Park BH 
Published: March 2017

Abstract
In the past decade, there has been great interest in the use of circulating cell-free DNA to help guide therapy decisions in clinical oncology. Recent work by our group and others suggests that circulating cell-free plasma tumor DNA offers advantages compared to tissue biopsies for mutation profiling. This concept of “liquid biopsy” may allow for a more global genomic picture of metastatic disease since blood serves as a reservoir for all metastatic sites. In addition, cell-free plasma tumor DNA can be measured serially and quantitatively, presenting the possibility of using circulating plasma tumor DNA as a biomarker to measure disease burden and response to therapies for both early and late stage disease. In this session, I will review historic and recent studies demonstrating the clinical potential of measuring cell-free plasma tumor DNA in breast cancer patients for early stage and metastatic disease. I will also outline future steps needed to translate liquid biopsies from research use to clinical practice, and recent work highlighting the first multi-institutional prospective clinical trial evaluating cell-free plasma tumor DNA in early stage breast cancer patients undergoing neoadjuvant chemotherapy.
Citation Format: Park BH. Cell free plasma tumor DNA in breast oncology [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 PL2.
Abstract S1-04: Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05)
Authors: Blok EJ , van de Velde CJH , Meershoek-Klein Kranenbarg EM , Putter H , van den Bosch J , Maartense E , van Leeuwen-Stok AE , Liefers G-J , Nortier JWR , Rutgers EJT , Kroep JR 
Published: March 2017

Abstract
Despite the success of adjuvant endocrine therapy in early breast cancer, approximately 50% of all recurrences still occur after the initial 5 years of follow-up. Earlier studies confirmed that endocrine therapy extension after 5 years of adjuvant tamoxifen with either tamoxifen or aromatase inhibitors up to 10 years leads to an improvement in survival. However, aromatase inhibitors are currently standard of care in the initial 5 years of adjuvant therapy, and the benefit of extended use beyond 5 years of AI based therapy is still debated. The randomized phase III IDEAL trial was designed to study the optimal duration of extended adjuvant endocrine therapy after the initial 5 years of any endocrine therapy.
Between April 2007 and November 2011, 1824 postmenopausal, HR-positive early breast cancer patients were included by 74 hospitals in the Netherlands. Enrolled patients earlier received 5 years of any endocrine therapy (87.9% AI based),completed this treatment no longer than 2 years before randomization, and did not have any recurrence at the moment of inclusion. The included patients were randomly allocated to either 2.5 or 5 years of extended letrozole (daily 2.5mg). Primary outcome was disease free survival (DFS), secondary endpoints were overall survival (OS), distant disease free survival (DDFS), contralateral breast cancer and safety.
Results & Discussion: Results will become available soon.
Citation Format: Blok EJ, van de Velde CJH, Meershoek-Klein Kranenbarg EM, Putter H, van den Bosch J, Maartense E, van Leeuwen-Stok AE, Liefers G-J, Nortier JWR, Rutgers EJT, Kroep JR. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006-05) [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 S1-04.
Abstract S2-01: Breast cancer risks associated with mutations in cancer predisposition genes identified by clinical genetic testing of 60,000 breast cancer patients
Authors: Couch FJ , Hu C , Lilyquist J , Shimelis H , Akinhanmi M , Na J , Polley EC , Hart SN , McFarland R , LaDuca H , Huether R , Goldgar DE , Dolinsky JS 
Published: March 2017

Abstract
Clinical genetic testing panels are broadly used to gather information about cancer predisposition in individuals with personal and/or family history of breast cancer. However, the involvement of several of the genes on clinical testing panels in predisposition to breast cancer, such as MRE11A and RAD50, has recently come into question. In addition, accurate risk estimates for breast and other cancer are not well defined for the majority of genes on testing panels. We studied 60,000 women diagnosed with breast cancer who were tested for germline cancer predisposing mutations using hereditary cancer gene panels. Information on personal and family cancer history, age of diagnosis, and ethnicity of patients was obtained from test requisition forms. Greater than 90% met National Comprehensive Cancer Network HBOC testing criteria. To estimate gene-specific risks for breast cancer, case-control analyses were performed comparing the frequencies of pathogenic mutations from Caucasian cancer cases with frequencies from Caucasian, non-Finnish, non-TCGA controls from the Exome Aggregation Consortium (ExAC) database. Mutations were detected in 9% of breast cancer patients. Twelve genes displayed a significant association (p&lt;0.05) with breast cancer. Nine of these genes, including ATM, RAD51D, NF1, and MSH6, were associated with moderate risk (RR&gt;2.0) of breast cancer and three genes (BRCA1, BRCA2, PALB2) were associated with high risk (RR&gt;5.0) of breast cancer. Cumulative age-dependent risk models were developed for each gene. This large clinical testing dataset of 60,000 women with breast cancer provides useful data for many predisposition genes previously lacking risk estimates, and should prove useful for clinical risk management of patients with inherited mutations in these genes.
Citation Format: Couch FJ, Hu C, Lilyquist J, Shimelis H, Akinhanmi M, Na J, Polley EC, Hart SN, McFarland R, LaDuca H, Huether R, Goldgar DE, Dolinsky JS. Breast cancer risks associated with mutations in cancer predisposition genes identified by clinical genetic testing of 60,000 breast cancer patients [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 S2-01.
Abstract A08: Leveraging technology to promote smoking cessation in primary care medical offices
Authors: Saad-Harfouche Frances G. , Rodriguez Elisa M. , Twarozek Annamaria Masucci , Widman Christy A. , Erwin Deborah O. , Underwood Willie , Fox Chester , Mahoney Martin C. 
Published: March 2017

Abstract
Purpose of the Study: While smoking represents the leading preventable cause of premature morbidity and mortality in the U.S., research has demonstrated that only a limited scope of cessation services are delivered to patients in many medical offices. We examined the use of an automated voice recognition (AVR) messaging intervention among smokers from primary care practices located in underserved urban and rural communities as a strategy to promote smoking cessation.
Methods: We utilized community-based participatory research (CBPR) involving smokers as a foundation for creating AVR messaging and partnered with urban and rural primary care medical office sites (n=7), including community clinics and federally qualified health centers. Current smokers, 18 years and older, who had an office visit within the previous 12 months, from these sites were used to create a smoker's registry (n=5,872). Between 2012 and 2014 participants were contacted over six month intervals using the AVR system. Smoker's registry data including demographic variables, medical office, and phone contact information. AVR results from each practice were aggregated and analyzed to assess cessation outcomes.
Results: Of the seven practice sites, a total of 5,872 smokers were accrued of whom 1,899 (32%) were reached through the AVR system. The average number of calls to smokers was 44 (median 51). 28% of the smokers reached were African American, 79% were age 40 and over, and 57% were female. Self-reported quit rates among reached smokers were 30%; quit rates were variable across selected variables.
Conclusions: An AVR based smoking cessation intervention provided added value beyond typical tobacco cessation efforts available in these primary care offices. This intervention required no additional clinical staff time and served to satisfy a component of patient center medical home requirements for many of these practices. Building partnerships with primary care medical offices can aid in the development and testing of community-based interventions such as smoking cessation delivered to medically underserved and diverse patient populations.
Citation Format: Frances G. Saad-Harfouche, Elisa M. Rodriguez, Annamaria Masucci Twarozek, Christy A. Widman, Deborah O. Erwin, Willie Underwood, III, Chester Fox, Martin C. Mahoney. Leveraging technology to promote smoking cessation in primary care medical offices. [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 A08.
Abstract A62: [Advocate Abstract:] Breast Cancer Screening Among African Immigrants and Refugees
Authors: Richards-Waritay Oni 
Published: March 2017

Abstract
“Breast Cancer Screening Among African Immigrants and Refugees” provides insight into the community-based breast cancer education and access to screening activities of the African Family Health Organization (AFAHO) for African women living in the greater Philadelphia area. The poster provides information about client recruitment; age, primary language and country of origin of clients; awareness about breast cancer before and after our educational activities and screening activities.
Citation Format: Oni Richards-Waritay. [Advocate Abstract:] Breast Cancer Screening Among African Immigrants and Refugees. [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 A62.
Abstract A65: Identifying perceptions of cancer prevention education needs and outreach strategies among young population in Puerto Rico
Authors: Ramos Francisco , Ramos Axel , Castro Eida , Jimenez Julio 
Published: March 2017

Abstract
Cancer is leading cause of death worldwide. It's well established that educating young population in prevention is better and more cost-effective, yet insufficient educational programs aimed at this population continues in Puerto Rico. Focus groups were developed to examine the opinions, perceptions and beliefs about cancer and cancer prevention education, and outreach strategies among young adults. The final goal of this study is to establish bases to develop a cancer educational program tailored to young population in Puerto Rico.
This qualitative study developed four focus groups (n=40), divided by age (18-20/21-24) and sex. The objectives listed were explored using 7 open-ended questions. The sessions were recorded, transcribed and analyzed with a content analysis perspective, using the constant comparative method, was performed to identify key themes. A thematic framework was established to classify and organize data according to key themes, concepts, and categories.
Four categories emerged from the transcribed material: concept related to cancer, concepts related to cancer prevention, need for cancer prevention education among young population, and challenges to cancer education among young population. When describing their perception of cancer, the participants mentioned words such as: death, horrible, suffering and struggle. Participants perceived prevention as a way to care for oneself and cancer prevention education as an educational strategy. They acknowledge the importance of cancer prevention education and recognized some of the challenges that educators face when educating young population. Suggested strategies included: social media, media, apps, classrooms, art and public figures. Strategies that don't work included: written materials, flyers, traditional workshops, radio campaigns.
These results confirm the importance of educating young population in cancer prevention. This study shows the relevance of to incorporate adolescent and young adults during the process to develop cancer prevention education programs under the community based participatory research approach.
Note: This abstract was not presented at the conference.
Citation Format: Francisco Ramos, Axel Ramos, Eida Castro, Julio Jimenez. Identifying perceptions of cancer prevention education needs and outreach strategies among young population in Puerto Rico. [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 A65.