bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-04-08: Identifying and characterizing human kinases for novel regulators of epithelial-mesenchymal transition in breast cancer cells
Authors: Li L , Azizian N , Li W 
Published: August 2014

Abstract
The epithelial-mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by breast cancer cells. Recently, a few kinases, such as FYN and c-Met, were reported to participate in regulating EMT. However, the roles of the majority of ∼700 human kinases in EMT and breast cancer progression are still unknown. Here we carried out human kinase cDNA screens to identify novel regulators of EMT. Many unknown EMT regulators and a few known ones such as PI3K, PDGFRA, FYN and c-Met, were found to up-regulate mesenchymal marker vimentin. Some also increase fibronectin and N-cadherin expression in kinase-transducted human mammary gland epithelial cells (HMLER). At the same time, these HMLER cells acquired mesenchymal phenotypes, such as increased in vitro migration activity, enhanced capability to survive and proliferate in growth factor deprivation condition or under drug treatments. RT-PCR results also exhibited increased expression of some EMT transcriptional regulators, such as ZEB1, Snail and Slug, which suggested our selected kinases may regulate EMT through these transcription factors. Interestingly, FACS analysis also showed a substantial increase in CD44hiCD24− population in these kinase-transducted HMLER cells. The increase of CD44hiCD24− mesenchymal phenotype could be attributed to increase of standard form CD44 (CD44s) and decrease of the variant form CD44 (CD44v8-10). And this alternation was associated with down-regulation of ESRP1 and ESRP2, two splicing factors that regulate CD44 splicing and EMT. Therefore, these selected kinases may be considered as novel regulators of EMT, and may aid the development of new prognostic markers or drug targets for breast cancer progression.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-04-08.
Abstract P5-08-01: Investigating the role of BRCA1 in sensitivity to GRN163L, a telomerase template antagonist
Authors: Phipps EA , Gryaznov SM , Herbert B-S 
Published: August 2014

Abstract
Background: BRCA1 is a tumor suppressor gene with a variety of functions related to safeguarding genomic integrity. The regulation of telomere length is also crucial in maintaining genomic stability, with critically short telomeres leading to telomere uncapping, end-to-end fusions, activation of the DNA damage response, and cell cycle arrest. The objective of this study was to determine whether GRN163L, a telomerase template antagonist currently in clinical trials, has enhanced activity in BRCA1 mutant breast or ovarian cancer cell lines compared to BRCA1 wild-type breast/ovarian cancer cell lines.
Methods: We utilized a panel of breast and ovarian cancer cell lines harboring both N-terminal and C-terminal BRCA1 mutations. This cell line panel included two isogenic cell line pairs reconstituted with wild-type BRCA1 (BRCA1 mutant: HCC1937 and UWB1.289; BRCA1 wild-type reconstituted: HCC1937+BRCA1 and UWB1.289+BRCA1). We assessed the effects of GRN163L or a mismatch oligonucleotide (MM) on telomerase activity and telomere length using the TRAP (Telomere Repeat Amplification Protocol) and TeloTAGGG (Roche) assays, respectively. Clonogenic survival assays, proliferation assays, and immunofluorescence were used to assess cellular responses to GRN163L and their molecular mechanisms.
Results: All cell lines tested exhibited a dose-dependent response to treatment with GRN163L, but not a mismatch control oligonucleotide. The majority of the cell lines tested showed gross morphological changes as early as 12 hours following inhibitor treatment. Progressive telomere shortening was evident after 3-week treatment with GRN163L, but not after treatment with MM. We observed differential sensitivity between BRCA1 mutant and wild-type isogenic cell line pairs to GRN163L in clonogenic survival assays. GRN163L pretreatment was synergistic with cisplatin in UWB1.289 and UWB1.289+BRCA1 cells. Simultaneous treatment with GRN163L and doxorubicin was synergistic in HCC1937 and HCC1937+BRCA1 cells. Long-term (12-week) treatment with GRN163L preferentially induced complete cell death in HCC1937 (BRCA1 mutant) breast cancer cells compared to HCC1937 cells reconstituted with wild-type BRCA1. One-week treatment with GRN163L was sufficient to induce γ-H2AX foci, with more γ-H2AX positive cells in the UWB1.289 BRCA1 mutant cell line.
Conclusions: Telomerase inhibition may be a viable treatment in BRCA1 mutant breast or ovarian cancers. These data provide insights into further investigations on the role of BRCA1 in the DNA damage response to GRN163L or combination treatment.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-08-01.
Abstract P5-10-09: Prediction of Trastuzumab treatment response for HER2-positive breast cancer by microRNA profiling
Authors: Sato F , Wang Z , Ueno T , Myomoto A , Takizawa S , Masuda N , Mikami Y , Shimizu K , Tsujimoto G , Toi M 
Published: August 2014

Abstract
[Background and Aim] Although Trastuzumab has been used for HER2(+) breast cancer, the treatment response of Trastuzumab therapy depends on unknown mechanisms among individual cases. In order to avoid unnecessary adverse events and to lighten financial burden for patients, pre-treatment prediction of trastuzumab treatment response would be beneficial for patients. Thus, in this study, we develop a prediction algorithm using microRNA expression profile of breast cancer tissues. [Materials and Methods] Eighty-three breast cancer patients who underwent trastuzumab-chemo combined therapy before operations were enrolled with written informed consent. FFPE specimens of pre-treatment core needle biopsy samples were collected, and regions containing cancer and adjacent stromal cells were laser-microdissected. Total RNA samples extracted from the microdissected specimens were subjected for microRNA microarray (3D-Gene®, Toray, Japan) analysis. Among these 83 patients, 39 cases had pCR (complete response in IDC regions regardless presense of DCIS without lymphnode metastasis), and the other 44 cases did not. According to the pCR/non-pCR information, we develop a prediction model using 35 signature microRNAs by a SVM technique. Prediction accuracy assessed by Leave-one-out validation was AUROC=0.889. The 35 signature microRNAs for trastuzumab treatment response included 7 out of 8 let-7 family members and miR-125a-5p/b-5p. [Conclusion] microRNA profile could predict treatment response of trastuzumab-chemo combined therapy for HER2(+) breast cancer, and the developed prediction algorithm might be a useful tool for clinical decision making.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-09.
Abstract P5-12-02: Tangled in the Breast Cancer Web: An Evaluation of the Usage of Web-based Information Resources by Breast Cancer Patients
Authors: Nguyen SKA , Ingledew P 
Published: August 2014

Abstract
Background: Increasingly cancer patients are researching web-based information to inform their clinical encounter with physicians. The use of the internet by breast cancer patients is incompletely characterized in the literature. The purpose of this study was to characterize the use of the internet by breast cancer patients describing the way they search for, and the impact of, web-based information on the clinical encounter.
Methods: From September 2011 to January 2012, breast cancer patients presenting at a tertiary cancer centre waiting to see their oncologist completed a written 23-question survey. Answers were closed and open-ended. Mixed-methods were used to interpret the quantitative and qualitative data.
Results: 81 patients were approached and 56 completed the survey. Forty-five (80%) respondents used the internet and of those, 32 (71%) respondents searched for breast cancer information. Patients who searched for internet breast cancer information (users) were younger than those who did not use the internet (p = 0.01). All respondents used Google as their principal search engine and “breast cancer” was the most commonly used search term. Twenty (62%) users accessed sites from a reputable source and 19 (59%) users viewed top search engine hits. To evaluate quality, 15 (47%) users referred to website author credentials and 13 (41%) users examined references. All users sought information with respect to treatment and three-quarters sought information on prognosis. The internet influenced treatment decision making for 30 (66%) users. Twenty-six (80%) users felt the information increased their knowledge of breast cancer and it influenced treatment decision making for 16 (53%) patients.
Conclusions: This study highlights search patterns and factors used by patients in seeking web-based breast cancer information. Physicians must appreciate that breast cancer patients use the internet for information and address discrepancies between the information sought and that which is available.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-12-02.
Abstract P5-13-01: Does empowering patients improve accrual to breast cancer trials?
Authors: Arnaout A , Kuchuk I , Bouganim N , Verma S , Clemons M 
Published: August 2014

Abstract
BACKGROUND Many international oncology professional and patient advocacy groups recommend that a minimum of 5% of eligible new patients should be entered into a clinical trial. Unfortunately, physician and patient related barriers translates to a much lower accrual rate in reality. We performed a prospective single arm pilot study evaluating the efficacy of implementing various physician and patient related strategies in enhancing clinical trial accrual.
METHODS All patients with newly diagnosed breast cancer seen at the breast surgery clinic were eligible for the study. Patients were offered information packages by their surgeons on non-surgical clinical trials that they might be eligible for, prior to their initial oncologist visit. Oncologists were informed of the information given to the prospective patient consultation via email and chart flagging. Patient were then given a questionnaire assessing the feedback on this method of introducing clinical trials. The primary outcome was the number of patients consenting to clinical trials. Secondary outcomes included the number of patients actually enrolling in clinical trials, screen failure rate, and overall patient satisfaction with this method of potentially enhancing accrual to clinical trials.
RESULTS 36 patients consented to this pilot study. 51% of oncologists mentioned the clinical trials to the patients. For those patients with which clinical trials were discussed, 72% went on to consent for a trial of which 31% were ultimately found to be ineligible (screen failure rate). The overall 14% clinical trial enrolment was significantly higher than our historical average of 7%. 100% of the patients found that the information package very helpful and was noted to reduce anxiety (39%) and empower (31%) the patients. 19% of the patients felt that this information should have been offered by the oncologist during the initial consultation as opposed to the surgeon prior to the oncology visit.
CONCLUSIONS The findings of this study could have a major impact on the way that cancer centres across the world approach patients for clinical trial options. Physicians remain an important barrier to trial accrual. The results of this study demonstrate that combined patient and physician centered approach to clinical trial enrolment may be the most effective.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-13-01.
Abstract P5-14-01: Accrual of underrepresented minority women to breast cancer clinical trials in Inland Empire, California.
Authors: Yuan Yuan , Uppala Padma Tadi , Morgan John W , Garberoglio Carlos A , Lum Sharon 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-14-01.
Abstract P5-15-01: Cost-effectiveness of gene expression profiling for ductal carcinoma in-situ (Oncotype DCIS Score)
Authors: Alvarado MD , Harrison BL , Solin LJ , Ozanne EM 
Published: August 2014

Abstract
BACKGROUND: Ductal carcinoma in-situ (DCIS) affects nearly 50,000 women each year. More than 75% of women who receive lumpectomy (BCS) for DCIS undergo whole breast radiation (XRT), which is known to prevent local recurrences. A molecular assay for DCIS has recently been validated, that identifies low-risk biology and may give insight into the need for adjuvant XRT. We sought to determine the cost-effectiveness of the Oncotype DCIS Score™ for risk stratification in newly diagnosed DCIS.
METHODS: We conducted a cost-effectiveness analysis of using this molecular assay (validated in the E5194 study) compared to standard clinical assessment to determine treatment recommendation for XRT. A Markov model was developed in TreeAge Pro 2011 and simulated relevant outcomes over a lifetime horizon for 55-year-old women. For those in the intervention arm who are stratified by the assay, it was assumed that 75% of women (low DCIS score) did not receive XRT and had local risk of recurrence (LRR) of 12%; 25% were intermediate or high risk by the DCIS score (LRR of 26%) and received 6 weeks of XRT with an assumed LRR of 13%. For those in the standard care arm who are stratified by clinical assessment, an assumed 25% did not receive XRT and had LRR of 15.4%; 75% received 6 weeks of XRT with an estimated LRR of 7.7%. Recurrence rates were based on ECOG 5194 and assumed 50% reduction with XRT. Utilities were derived from literature. Direct medical costs were obtained from Medicare fee schedule; indirect costs (time and transportation for XRT) were ascertained.
RESULTS: On average, the intervention (assay) strategy was less costly than the clinical assessment strategy by approximately $1000/patient, with similar life expectancies (17.15 vs 17.11, respectively) and quality-adjusted life-years (QALYs) (16.777 vs 16.789). The incremental cost-effectiveness ratio (ICER) for changing strategy from the assay to clinical assessment was approximately $95,000/QALY, at the upper limit of the societal accepted willingness-to-pay threshold.
CONCLUSIONS: Based on the conservative assumptions that the benefit of XRT is independent of biology and that at least 75% of patients in E5194 would typically be offered XRT, the assay strategy is more cost-effective than standard clinical assessment. Additional research is needed to better understand health state utilities associated with less treatment as it pertains to risk of recurrence. Further validation studies of the assay are needed to accurately assess radiation benefit across all risk groups.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-01.
Abstract P5-15-03: Cost-effectiveness of ‘radioguided occult lesion localization’ (ROLL) versus ‘wire-guided localization’ (WGL) in breast conserving surgery for non-palpable breast cancer: results from a randomized controlled multicentre trial
Authors: Postma EL , Koffijberg E , Verkooijen HM , Witkamp AJ , van den Bosch MA , van Hillegersberg R 
Published: August 2014

Abstract
Background: Accurate pre-operative localization of non-palpable breast cancer is essential to achieve complete resection. Radio-guided occult lesion localization (ROLL) has been introduced as an alternative for wire-guided localization (WGL). Although efficacy of ROLL has been established in a RCT, cost-effectiveness of ROLL compared with WGL is not yet known.
Objective. To determine whether ROLL has acceptable cost-effectiveness compared with WGL.
Methods. An economic evaluation was performed alongside a randomized controlled trial (ClinicalTrials.gov, number NCT00539474). Women (&gt;18 years) with histologically proven non-palpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomized to ROLL(n = 162) or WGL (n = 152). Empirical data on direct medical costs was collected, and changes in quality of life were measured over a 6 months period. Bootstrapping was used to assess uncertainty in cost-effectiveness estimates, and sensitivity of the results to the missing data approach was investigated.
Results. In total, 314 patients with 316 invasive breast cancers were enrolled. On average ROLL required the same time as WGL for the initial procedure (119 vs. 118 min.), resulted in a 7% higher re-interventions risk (27% vs. 20%, p = 0.163), a 13% higher complication risk (30% vs. 17%, p = 0.006) but showed similar health effects (difference 0.00 QALYs 95%CI (−0.04 to 0.05). Total costs were also similar for ROLL and WGL (+ €26 per patient 95% CI-250 to 311).
Conclusion. ROLL is comparable to WGL with respect to both costs and quality of life, and will therefore not lead to more cost-effective medical care.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-03.
Abstract P5-17-01: Bevacizumab (B) in the adjuvant treatment of breast cancer - first toxicity results from Eastern Cooperative Oncology Group trial E5103.
Authors: Miller KD , O'Neill A , Dang C , Northfelt D , Gradishar W , Sledge GW 
Published: August 2014

Abstract
Background: A previous feasibility trial (E2104 – Ann Oncol 23(2):331–7,2012) suggested incorporation of B into anthracycline-containing adjuvant therapy was feasible but ongoing cardiac monitoring was required to define the true impact of B on cardiac function.
Methods: Patients (pts) were assigned 1:2:2 to one of three treatment arms. In addition to doxorubicin and cyclophosphamide followed by weekly paclitaxel, patients received either placebo (Arm A – AC&gt;T) or B during chemotherapy (Arm B - BAC&gt;BT), or B during chemotherapy followed by B monotherapy (15 mg/kg q3wk) for an additional 10 cycles (Arm C – BAC&gt;BT&gt;B). Randomization was stratified and B dose adjusted for choice of AC schedule (classical q3wk − 15 mg/kg; dose dense(dd) q2 wk − 10 mg/kg). When indicated, radiation and hormonal therapy were administered concurrently with B (for Arm C pts). The primary cardiac endpoint was the incidence of clinically apparent cardiac dysfunction (CHF)defined as symptomatic decline in left ventricular ejection fraction (LVEF) to below the lower limit of normal (LLN) or symptomatic diastolic dysfunction as assessed by independent review. Cumulative toxicity data as of Jan 23, 2012 are presented.
Results: From 11.07 to 2.11, 4994 pts were enrolled. Median age was 52; 80% received ddAC. Chemotherapy associated toxicities including myelosuppression (Grade 4 neutropenia 16/20/19%) and neuropathy (Grade ≥ 3 8/8/8%) were similar across all arms. Grade ≥ 3 hypertension/thrombosis/proteinuria/hemorrhage was reported by 7/3/&lt;1/&lt;1% of B-treated pts. 99 pts developed CHF, most commonly reported at the post-AC or post-T evaluation. After a median follow-up of 26 months, the cumulative incidence of clinical CHF at 15 months from randomization in Arm A/B/C was 1.0/1.7/2.9% respectively. Median age of CHF pts was 57; median baseline LVEF of CHF pts was 60.

Conclusion: Incorporation of B into anthracycline and taxane containing adjuvant therapy results in a significant but small increase in clinical CHF. The rate of clinical CHF is similar to that predicted by E2104 (2.5–2.9%) and reported In the FDA label for anthracycline pre-treated pts(3.8%). No unexpected toxicities were encountered.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-01.
Abstract P5-17-07: Influence of bevacizumab on local-regional recurrence in triple negative breast cancer
Authors: Prendergast BM , De Los Santos JF , Barrett OC , Forero A , Falkson CI , Urist MM , Krontiras H , Bland KI , Meredith RF , Keene KS , You Z , Carpenter JT 
Published: August 2014

Abstract
Background: Triple negative breast cancer (TNBC) comprises 15–20% of newly diagnosed invasive breast cancers and has been associated with an elevated risk of both local-regional recurrence (LRR) as well as distant failure. Bevacizumab (BEV) has been shown to improve pathologic complete response rates in the setting of neoadjuvant chemotherapy (NCT), but its effect on LRR remains undefined. This study reports the impact of adding BEV to standard breast cancer therapy in TNBC patients treated at a single institution.
Methods: One hundred and eighty-five consecutive TNBC patients treated at the University of Alabama Birmingham from May 2005 to August 2010 were reviewed. Thirty-one TNBC patients treated with chemotherapy (CT) and BEV on prospective studies were matched (1:2) with 62 TNBC patients treated with CT alone, controlling for age, stage, and use of radiation (RT). The Kaplan-Meier method was used to estimate LRR, distant metastasis-free survival (DMFS), and overall survival (OS), and cohorts were compared using Cox proportional hazards models and the 2-sided log-rank test.
Results: Mean age was 47 and 46 years in the cohorts with and without BEV, respectively. Stage in each cohort was as follows: 32% stage I, 61% stage II, and 7% stage III. Use of adjuvant RT was 81% in each cohort (25/31 BEV, 50/62 no BEV). BEV was delivered with NCT in 17 patients (55%) and with adjuvant CT in the remaining 14 patients (45%). Eleven patients (35%) completed an additional 1 year of maintenance therapy with BEV. LRR occurred in 2 (6%) patients treated with BEV vs. 16 (26%) treated with CT alone (HR = 0.25, 95% CI 0.06–1.07, p = 0.04). Distant recurrence occurred in 3 (10%) patients treated with BEV vs. 11 (18%) patients in the CT group HR=0.6, 95% CI 0.2–1.8, p = 0.48). There were 2 (6%) deaths in the BEV group vs. 12 (19%) in the CT alone group (HR = 0.55, 95% CI 0.13–2.3, p = 0.19).
Conclusions: In a matched-pair analysis of TNBC patients, the addition of BEV to conventional breast cancer management was associated with a reduction in LRR. Further prospective study is necessary to examine the impact of BEV on local-regional control in TNBC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-07.