bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-09-01: Central Ki67 analysis as a predictor for adjuvant capecitabine efficacy in early breast cancer (EBC) subtypes in US oncology trial 01062
Authors: O'Shaughnessy J , Koeppen H , Crockett M , Lackner M , Spoerke JM , Wilson T , Levin MK , Pippen J , Paul D , Stokoe C , Blum J , Holmes FA , Lindquist DL , Krekow L , Vukelja SJ , Sedlacek S , Rivera R , Brooks RJ , McIntyre KJ , Schwartz JE , Jones S 
Published: August 2014

Abstract
Background: USON 01062 (O’Shaughnessy J, et al. Proc SABCS, 2010, abst S4-2) showed no improvement in the primary endpoint of disease-free survival (DFS) (median FU 5 yrs: HR 0.84, 95% CI: 0.67-1.05; p = 0.125) with the addition of capecitabine (X) to standard adjuvant chemotherapy, but showed improvement in OS (HR 0.68, 95% CI: 0.51-0.92; p = 0.011). Exploratory analysis of local pathology-assessed Ki67 suggested benefit from adjuvant X in pts with more highly proliferative cancers with Ki67 ≥ 10% (Pippen J et al. Proc ASCO, 2011, abst 500). The objective of this study is to determine whether centrally-performed Ki67 IHC results corroborate or refute this finding.
Methods: 2610 pts with resected high risk EBC were randomized to receive 4 cycles of AC (doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2) IV every 3 wks for 4 cycles followed by either docetaxel 100mg/m2 IV or docetaxel 75mg/m2 IV plus X 825mg/m2 PO bid for 14 days every 3 wks for 4 cycles. Archival primary breast cancer tissue was collected on 2000 pts for predictive biomarker analyses. Central Ki67 IHC was performed using the anti-Ki67 monoclonal antibody SP6 and was read by one pathologist (HK) according to published recommendations (Dowsett M, et al. JNCI 103:1-9, 2011).
Results: Central Ki67 IHC has been performed on 1440 pts who had centrally-validated informed consents. The distribution of% Ki67-positive cells by locally-assessed ER/HER2 subtype is shown below. 45% of HR+ HER2- BCs had a Ki67 ≤ 10%, while 24% had a Ki67 11% to 20%, and 31% had a Ki67 &gt; 20%. The concordance between the local vs central Ki67 results was low at 46% for Ki67 &lt;10%, 49% for Ki67 10%-20%, and 76% for Ki67 &gt; 20%. The central Ki67 results tended to be higher than the local testing results. Central mRNA classifiers were developed for ER, PR, HER2 and Ki67 using Fluidigm Microfluidics Dynamic Arrays and correlate highly with central IHC assessment of these markers.
Conclusions: HR+ HER2- EBC is enriched for cancers with a low proliferative rate, a group of pts unlikely to benefit from the cell cycle-specific cytotoxic agent, capecitabine. Analyses of the impact of adjuvant X added to AC/T in EBC pts according to ER status, and according to Ki67 (analyzed as a binary and continuous variable) will be performed prior to SABCS, 2013.
Number of Patients% Ki67 Pos CellsTotal *HR+TNHER2+/HR+HER2+/ HR-0-104163622222711-151391066151016-20126871615821-3018411539201031-1005751403423555Total144081042510790*Totals do not equal sum of subtype categories due to missing HER2 information
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-09-01.
Abstract PD4-6: Combined analysis of gene expression, DNA copy number and mutation profiling data to display biological process anomalies in individual cancers
Authors: Shi W , Balazs B , Qi Y , Györffy B , Wang B , Liu C-G , Shiang CY , Valero V , Moulder-Thompson S , Avritscher R , Powis G , Hortobagyi GN , Natowicz R , Wali V , Weinstein J , Symmans WF , Pusztai L 
Published: August 2014

Abstract
Background: The goal of this analysis was to develop a computational tool that integrates gene expression, DNA copy number and sequence abnormalities in individual cancers in the framework of biological processes.
Methods and Findings: We used the hierarchical structure of the Gene Ontology (GO) database to create a reference network and projected mRNA expression, DNA copy number and mutation anomalies detected in single samples into this space. We applied our method to 59 breast cancers where all three types of molecular data were available. Each cancer had a large number of disturbed biological processes. Locomotion, multicellular organismal process and signal transduction pathways were the most commonly affected GO terms but the individual molecular events were different from case-to-case. Estrogen receptor-positive and -negative cancers had different repertoire of anomalies. We tested the functional impact of 27 mRNAs that had overexpression in cancer with variable frequency (&lt;2-42%) using an siRNA screen. Each of these genes inhibited cell growth in at least some of 18 breast cancer cell lines.
Conclusions We developed a free, on-line software tool (http://netgoplot.org) to display the complex genomic abnormalities in individual cancers in the biological framework of the GO biological processes. We show that each cancer harbors a large number and unique combination of pathway anomalies, the individual molecular events that underlie the pathway level disturbances vary from case-to-case. Our in vitro experiments indicate that even rare case-specific molecular abnormalities can play a functional role and driver events may vary from case to case depending on the constellation of other molecular anomalies.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD4-6.
Abstract PD6-7: The prognostic relevance of disseminated tumor cells (DTC) form the bone marrow (BM) in different molecular subtypes of primary breast cancer (PBC) patients
Authors: Hartkopf AD , Taran F-A , Brucker S , Hahn M , Wallwiener D , Becker S , Solomayer E-F , Wallwiener M , Fehm T 
Published: August 2014

Abstract
Background:
The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (PBC) patients is associated with a worsened prognosis. This is the largest single-center study that determines the impact of DTC on disease free (DFS) and overall survival and compares it to predefined molecular subtypes of PBC.
Methods:
BM aspirates were collected from patients that underwent surgery for PBC at Tuebingen University Hospital, Germany between 01/2001 and 01/2013. DTC were identified by immunocytochemistry (pancytokeratin antibody A45/B3) and cytomorphology. Patients were divided into three subgroups based on immunohistochemical staining of the primary tumor: (1) hormone receptor-positive/HER2-negative (HR+/HER2-), (2) HER2-positive (HER2+), and (3) HR-negative/HER2-negative (HR-/HER2-) patients. The DTC-status was compared to other prognostic factors by use of the chi-squared test and survival was analyzed in an univariate (log-rank test) and multivariate analysis (cox regression).
Results:
3,141 patients were available for this retrospective analysis. Of these 803 (26%) were DTC-positive. DTC-positivity was associated with larger tumors (p&lt;0.001), positive lymph nodes (p = 0.001), ER-negative (p = 0.016) and PR-negative (p&lt;0.001) patients. DTC-positive patients were at an increased risk of death (median OS of DTC- vs. DTC+ patients: n. r. (not reached) vs. 115 (95% CI: 113-118) months, p = 0.004) and disease relapse (median DFS was n. r. in either groups, p&lt;0.001). Independent factors for OS / DFS were DTC-status, menopausal-status, tumor size, nodal-status, ER-status and PR-status / DTC-status, tumor size, nodal-status and ER-status. In the subgroup analysis (median OS was n. r. in either groups), the DTC-status had a significant impact on OS only within the HR+/HER2- subgroup (p = 0.004) and on DFS in the HR+/HER2- (p = 0.005) and the HER2+ subgroup (p&lt;0.001).
Conclusion:
This study confirms the strong and independent prognostic value of DTC-determination in primary breast cancer patients. With respect to analysis of different molecular subtypes, the DTC-status was found to be of prognostic significance especially in HR+/HER2- patients. The DTC-status might help to identify HR+/HER2- patients that are at an increased risk of death or disease relapse and thus in need for an aggressive adjuvant treatment.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-7.
Abstract PD6-8: Prognostic value of disseminated tumor cells according to ER/PR and HER2 status in non-metastatic breast cancer
Authors: Lee JS , Magbanua MJM , Moore AP , Esserman LJ , Park JW 
Published: August 2014

Abstract
Background: Disseminated tumor cells (DTCs) in the bone marrow from breast cancer patients have been reported as a prognostic factor. We evaluated prognostic value of DTCs in non-metastatic breast cancer according to ER/PR and HER2 status.
Methods: Bone marrow aspirates were obtained from 607 non-metastatic breast cancer patients at the time of primary surgery between 1999 and 2012. DTCs were identified via immunomagnetic enrichment followed by flow cytometry (IE/FC) using anti-EpCAM monoclonal antibody (mAb). The relation between high DTC count and clinical outcome was analyzed with ER/PR and HER2 status. Patients whose DTC count is in the above 80th percentile were considered as higher DTCs.
Results: Median and mean DTC count were 7.2 and 24.5 cells/mL and 80th percentile was 18.5 cells/mL. Higher DTC group (&gt; = 18.5 cells/mL) showed impaired disease free survival (DFS; P = .019, log-rank) after median follow-up of 59 months. This poorer outcome in higher DTC group was observed mainly in ER(-) patients and triple negative patients with lower DFS (P = .002 and 018) and overall survival (OS; P = .004 and .012). There was no significant survival difference in ER(+), HER2(+), or ER(+)/HER2(-) patients.
Conclusion: High DTCs in non-metastatic breast cancer is associated with poor clinical outcome, especially in ER(-) or triple negative patients. However, DTCs is not related with prognosis in other ER/HER2 status groups.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-8.
Abstract S6-07: Genomic characterisation of metastatic samples from breast cancer patients using next generation sequencing
Authors: Bachelot T , Lefebvre C , Campone M , Levy C , Arnedos M , Bonnefoi H , Dieras V , Treilleux I , Goncalves A , Clapisson G , Jimenez M , Andre F 
Published: August 2014

Abstract
Background: Although several studies have reported genomic characterisation of primary breast tumors, little is known about the genomic alterations of the metastatic tissues. Breast cancer patients who were prospectively enrolled in a trial (SAFIR01) underwent a biopsy of metastasis. The primary aim of this biopsy was to drive the treatment according to the results of whole genome CGH arrays and sanger sequencing on two genes (PIK3CA and AKT1). The results of the clinical trial were previously reported (André et al ASCO 2013). The secondary goal of the biopsies was to perform genomic characterisation of metastases in breast cancer patients. Here we report the analyses of such metastatic samples using next generation sequencing (NGS) approaches.
Patients and methods: Two approaches were applied. In order to describe the incidence of targetable genomic alterations, we performed in depth targeted sequencing on 100 genes (200x coverage) using Illumina HiSeq 2000 (DNA vision). This analysis was performed on 240 metastatic samples. The second approach was more exploratory and aimed at discovering new genes involved in the metastatic process and/or resistance to therapies. In order to achieve this goal, we performed whole exome sequencing in 100 pairs of metastatic tissue (100x) and normal DNA (Integragen Inc, Hiseq platform). Finally, phosphor-S6K staining was performed in 300 samples in order to explore the activation status of mTOR pathway in metastatic disease, and to correlate with genomic data.
Results: Targeted sequencing was performed on 240 metastatic samples in order to report the prevalence of targetable genomic alterations in metastatic breast cancer. Results are available for the first 159 samples. In addition to the already reported PIK3CA (26%) and AKT1 mutations (4%), NGS identified mutations of PTEN (4%), ERBB2 (2%), K-Ras (1%), ATM (2%), CDH1 (2%), GATA3 (2%), PTPN11 (1%), PTPRD (1%), ROS1 (1%). Results on the 81 samples, together with whole exome sequencing (n = 100) and phosphoproteins are being analysed and results will be available mid-november 2013.
Conclusion: This is the first large study that aims at defining the genomic landscape of metastatic samples. Results will provide insights into the prevalence of targetable genomic alterations in metastatic tissue, together with candidate genes involved in the metastatic process and resistance to therapies.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S6-07.
Abstract A16: Promoting colorectal cancer screening in urban, minority populations with community health workers.
Authors: Sanchez Martha , Ashby-Thompson Maxine , Jacobson Judith S. , Hepburn Patricia , Grann Victor E. 
Published: August 2014

Abstract
Background: Colorectal cancer (CRC) is the third most common cancer and cause of cancer-related death in the United States. Screening prevents not only mortality but also the occurrence of CRC. Our group reaches out to and educates members of our predominantly low-income Hispanic and African American community about cancer treatment, research, and prevention by establishing partnerships with community-based organizations (CBOs) and training community health workers (CHWs). In 2010, we learned that relatively few CBO clients had been screened or intended to be screened for CRC, and that the CHWs also were not well informed about CRC.
Methods: We developed an enhanced training program about CRC for CHWs and their clients. We renewed two of our CBO partnerships, added one more, retrained some previously trained CHWs, and recruited and trained CHWs from the new CBO. We developed a new pre- and post-training 10-question instrument to evaluate what the CHWs already knew and what they learned from our training. We compared the CHWs' average scores (proportions of correct answers) before and after the training. Further training was conducted to reinforce CHWs' knowledge. Using focus groups and community-based participatory research methods with the CHWs, we then developed two educational interventions that the CHWs will implement in the coming months.
Results: Fifteen CHWs were trained or retrained. Most of the participating CHWs had previously received our training. All of them answered at least 6 of the 10 questions correctly both before and after the training, but average scores improved from 75% correct before the training to 82% correct afterwards.
Next steps: Each CHW will educate 20 clients (n=300) aged 50+ years about CRC screening and attempt to schedule them for screening. In the two intervention groups, we will compare proportions of clients who receive CRC screening. Results will be disseminated to the community in our quarterly community newsletter, a report to the CBOs, and a press release to the local media.
Citation Format: Martha Sanchez, Maxine Ashby-Thompson, Judith S. Jacobson, Patricia Hepburn, Victor E. Grann. Promoting colorectal cancer screening in urban, minority populations with community health workers. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A16.
Abstract A32: Do theoretical mediators differentiate adherent and nonadherent American Indian mammographic screeners? Preliminary results from one tribe.
Authors: Petersen Wesley , Nicometo Ann M. 
Published: August 2014

Abstract
Purpose: The study purpose is to learn whether theoretical mediators (Planned Behavior/Reasoned Action, Social Norms, Social Support, Social Networks, Health Beliefs, Health Literacy) can be used to distinguished American Indian women who are adherent with Indian Health Service (IHS) mammographic screening guidelines from those who are not adherent with these guidelines. Women in the Bemidji Area of the Indian Health Service have mammographic screening rates much lower than the IHS average for all IHS areas. Bemidji Area women are diagnosed at later stage and have higher mortality than is seen in the overall IHS. Our ultimate goal is to develop interventions to increase adherence among non-adherent screeners. Experimental procedures: In phase one, we have identified 64 women for interviews. Based on women's risk factors and screening histories, women were assigned to one of four groups: high risk/adherent, low risk/adherent, high risk/non-adherent, and low risk/non-adherent. Our goal is to have 16 women in each group. Currently, we have interviewed and conducted preliminary analysis of 19 women (4 higher risk/ adherent; 7 lower risk/non-adherent, 4 higher risk, non-adherent, 4 lower risk/adherent). Interview responses have been coded for themes, then categorized and descriptively quantified. Preliminary results: Adherent and non-adherent mammographic screeners can be differentiated by: 1) Theory of Planned Behavior (personal attitudes toward screening; perceived attitudes of family/friends and tribe toward annual screening; and past screening behavior). 2) Social Norms (perceptions of general health of respondents, family/friends, and tribe; health behaviors; barriers to screening; influences on attitudes and behaviors; healthy behaviors; health values; perceptions of common cancers among tribal members and women; the mammography experience; and influential members within social networks). 3) Social Support (emotional support for worry and fear and companionship. 4) Health Beliefs (susceptibility and severity of cancer). In other regards, these mediators and Health Literacy do not distinguish between adherent and non-adherent screeners. Conclusions: Theoretical mediators may be a useful way to distinguish between adherent and non-adherent screeners and point to potential avenues to intervene in the non-adherent population of American Indian women.
Citation Format: Wesley Petersen, Ann M. Nicometo. Do theoretical mediators differentiate adherent and nonadherent American Indian mammographic screeners? Preliminary results from one tribe. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A32.
Abstract A37: Discovery of novel luteinizing hormone releasing hormone (LHRH) peptides as a nanotherapeutic targeting drug delivery system for prostate, ovarian, breast, and cervical cancers.
Authors: Olivos David J. , Saunders Mary R. , Li Yuanpei , Awwad Nasir Al , Lam Kit S. 
Published: August 2014

Abstract
Luteinizing hormone releasing hormone receptors (LHRHR) are overexpressed on cancer cell surfaces of the prostate, ovary, breast, and cervix'each of which reflect a health disparity in the African American, Latino, and Asian communities. Chemotherapy in combination with surgery, radiation, and hormone therapy is commonly used to treat these cancer types. Novel LHRH analogues have been discovered and optimized to selectively deliver cytotoxic agents to the tumor mass as a means to improve therapeutic index and efficacy while sparing normal tissues. We have synthesized several generations of 20% down-substituted One Bead One Compound (OBOC) focused libraries composed of select D- and L- amino acids, carboxylic acids, sulfonyls, and isocyanates, and screened under highly stringent conditions against LHRHR positive, negative, and overexpressing cell lines. Our novel LHRH analogues out performed clinical LHRH analogues [d-Trp6] LHRH and [d-Lys6] LHRH in binding affinity against LHRHR in vitro. Cell adhesion ligands for prostate (PC3N, PC3M), breast (MDA MB-231, MCF7), ovarian (A2780), and cervical cancer (HeLa, SiHa) have been discovered, and their use as tumor-homing agents for diagnostic and therapeutic purposes is being explored in xenograph models. Our preliminary studies utilizing our docetaxel loaded disulfide cross-linked nanoparticle platform demonstrate a therapeutic efficacy against PC3M-luc subcutaneous xenograft. We believe these drug loaded nanocarriers will be able to target and kill cancer cells more efficiently while minimizing side effects compared to current treatments when decorated with our highly specific and high affinity LHRH ligands. This approach is a promising strategy for future clinical development.
Citation Format: David J. Olivos, III, Mary R. Saunders, Yuanpei Li, Nasir Al Awwad, Kit S. Lam. Discovery of novel luteinizing hormone releasing hormone (LHRH) peptides as a nanotherapeutic targeting drug delivery system for prostate, ovarian, breast, and cervical cancers. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A37.
Abstract A61: Characterizing inflammatory breast cancer among Arab Americans in the California, Detroit, and New Jersey Surveillance, Epidemiology and End Results (SEER) registries (1988-2008).
Authors: Hirko Kelly A. , Soliman Amr S. , Banerjee Mousumi , Ruterbusch Julie , Harford Joe B. , Chamberlain Robert , Graff Jon J. , Merajver Sofia D. , Schwartz Kendra 
Published: August 2014

Abstract
Introduction: Inflammatory breast cancer (IBC) is characterized by an apparent geographical distribution in incidence, being more common in North Africa than other parts of the world. Despite the rapid growth of immigrants to the United States from Arab nations, because a racial category is rarely appropriated for this group, little is known about disease patterns among Arab Americans. The aim of this study was to describe the proportion of IBC among different racial groups, including Arab Americans from the Detroit, New Jersey and California Surveillance, Epidemiology and End Results (SEER) registries.
Methods: We utilized a validated Arab surname algorithm to identify women of Arab descent from the SEER registries. Differences in the proportion of IBC out of all breast cancer and IBC characteristics by race and menopausal status were evaluated using chi-square tests for categorical variables, t-tests and ANOVA tests for continuous variables, and log-rank tests for survival data. We modeled the association between race and IBC among all women with breast cancer using hierarchical logistic regression models, adjusting for individual and county-level variables.
Results: Statistically significant differences in the proportion of IBC out of all breast cancers by race were evident. In a hierarchical model, adjusting for age, estrogen and progesterone receptor, human epidermal growth receptor 2, registry and county-level socioeconomic position, Arab-Americans (OR=1.5, 95% CI=1.2,1.9), Hispanics (OR=1.2, 95% CI=1.1,1.3), Non-Hispanic Blacks (OR=1.3, 95% CI=1.2, 1.4), and American Indians/Alaskans (OR=1.9, 95% CI=1.1, 3.4) had increased odds of IBC, while Asians had decreased odds of IBC as compared to Non-Hispanic Whites (OR=0.6, 95% CI=0.6, 0.7).
Conclusions: IBC may be more common among certain minority groups, including Arab American women. Understanding the descriptive epidemiology of IBC by race may generate hypotheses about risk factors for this aggressive disease. Future research should focus on etiologic factors that may explain these differences.
Citation Format: Kelly A. Hirko, Amr S. Soliman, Mousumi Banerjee, Julie Ruterbusch, Joe B. Harford, Robert Chamberlain, Jon J. Graff, Sofia D. Merajver, Kendra Schwartz. Characterizing inflammatory breast cancer among Arab Americans in the California, Detroit, and New Jersey Surveillance, Epidemiology and End Results (SEER) registries (1988-2008). [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A61.