bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiofrequency Ablation in Breast Cancer.
Authors: Tzoracoleftherakis E. , Sdralis E. , Maroulis J. , Ravazoula P. 
Published: December 2010

Abstract
Background: Radiofrequency ablation (RFA) of breast tumors is characterized by variable efficiency. Cell viability is principally evaluated by NADH-diaphorase and Hematoxylin-eosin (H&E) staining techniques.Methods: Twenty patients with breast cancer, 20.7 ± 9.14mm in diameter, underwent RFA of the tumor and of the margin of surrounding breast tissue. RFA was based on the radiofrequency impedance-switching algorithm. The algorithm was based on an internally cooled probe, which carried out algorithm-guided deposition of heat in a pulse-cycle fashion and under continuous monitoring of the desiccation status of the ablated site to avoid tissue charring (until its impedance level reached 30Ω above the baseline level or a maximum time interval (tmax) was reached). A minimum time interval of 5 seconds was set as the duration of time that the electrode must be off. If the cycles of power application occurred too rapidly, the power was diverted to the 150Ω resistance load for the remainder of the 5-second interval. Surgical resection was the next step. Sixteen patients underwent quardzantectomy (five with axillary lymph node dissection) and four unilateral total mastectomy. In fifteen patients SLNB was searched and identified (ten negative, four positive and one failure). The ablated tumor tissue was histologically examined and Ki67 immunohistological staining was applied to evaluate cellular proliferation, invasion and survival.Results: The mean time of operation was 119.47 ± 23.35minutes.The mean time of RFA was 12 - 15minutes. One patient had a post-operative complication (trauma infection). All twenty patients had a positive Ki67 immunohistochemical staining mean value of 28.79 ± 21.42, before RFA. The post-RFA Ki67 expression was zero in sixteen patients. In three patients no residual tumor cells were found and in one patient the Ki67 expression was under five percent. Recurrence developed in zero patients, to date (follow up time: 22.5 ± 2.3 months).Conclusion: Ki67 evaluation is a targeting indicator of viability of malignant cells after lesion RFA of breast tumors. RFA is able to provide satisfactory local control in breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2106.
Differences in Dielectric Properties between Malignant and Normal Breast Tissue: Preliminary Results of the MicroBlate® Study.
Authors: Chaudhry A. , Baruah B. , Goyal A. , Kink T. , Young P. , Douglas-Jones A. , Mansel R. 
Published: December 2010

Abstract
Background: Minimally-invasive microwave ablation techniques for the management of breast diseases are an emerging technology. These techniques rely, to a certain extent, on the difference in dielectric properties of normal and malignant human tissue. In our unit, we are currently studying the efficacy of a new microwave based technology, MicroBlate®, which has the unique feature of being able to measure tissue impedance and deliver microwave frequency impulse to tissues based on this impedance feedback. In this study we have compared the dielectric properties of normal and malignant breast tissues using this probe to establish proof of principle.Methodology:Impedance of freshly excised mastectomy and reduction specimens were measured ex-vivo using the MicroBlate® probe. This probe was attached to the end of the precision open-ended co-axial cable connected to an Agilent 4-port PNA-L Microwave network analyser (10MHz – 20 GHz). Impedance (Z) was intially recorded as two values which are vector quantities: real (R), which reflects the tissue resistance, and imaginary (X), a measure of tissue reactance. The overall impedance was then calculated using the standard mathematical formula, Z= √(R2+X2). Measurements were performed on adipose, glandular and malignant breast tissue immediately following surgical excision. Differences in the impedance values between these tissue types were calculated and the results analysed using appropriate statistical tests.Results:Our study shows a measurable difference in the dielectric properties of malignant and normal breast tissue. Our data supports the technological basis of MicroBlate®, a minimally invasive microwave ablation technology with impedance feedback, further ex-vivo studies are needed to determine its efficacy in ablating benign and malignant breast tissue. 28 patients undergoing elective mastectomy (n=26) and reduction (n=2) were included in this study between Feb – May 2009. Of the 26 patients undergoing mastectomy, 19 had invasive malignancy and the remaining 7 had in-situ malignancy only. The median age of the patients was 58 years (range 22-80 years). The average impedance of adipose tissue was 29.3 ± 6.9W, glandular tissue was 31.1 ± 6.1W and for malignant tissue was 49.6 ± 9.3W (Mann Whitney U p value &lt;0.001). The average difference between impedance of malignant and glandular tissue in individual patients was 19.6 ± 8.6W.Conclusions:Our study shows a measurable difference in the dielectric properties of malignant and normal breast tissue. Our data supports the technological basis of MicroBlate®, a minimally invasive microwave ablation technology with impedance feedback, further ex-vivo studies are needed to determine its efficacy in ablating benign and malignant breast tissue.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3099.
Evaluation of the Phytochemical Anethole as an Anti-Tumor Agent in MCF-7 Cells.
Authors: Chen C. , De Gasperi M. , Salcedo R. , Cavazos D. , deGraffenried L. 
Published: December 2010

Abstract
Background: Chinese herbal medicines have gained considerable interest from the cancer community as potential anti-tumor agents. Both clinical as well as pre-clinical studies have demonstrated that certain Chinese herbal medicines can improve survival, increase tumor response, improve quality of life, and reduce chemotherapy toxicity. The specific mechanisms by which these compounds mediate their effects remain largely unknown, inhibiting their development as clinical agents. One such compound is anethole. Anethole is an aromatic compound that occurs widely in nature as a component of anise, fennel anise myrtle, licorice, and star anise and is used in traditional Chinese medicine as an anti-inflammatory agent. Anethole has been identified as one of the potential phytochemicals with anti-cancer activities that could be developed into clinical treatments for breast cancers.Objective: In this current study, we evaluated the effect of anethole on physiological responses and specific survival pathways in human breast cancer MCF-7 cells.Results: Cell proliferation and cell survival were suppressed in a dose-dependent manner in response to anethole treatment, but these dosages had differential effect on specific pro-survival pathways. Anethole increased the cleavage of Poly (ADP-ribose) polymerase (PARP), suggesting an increase in apoptotic activity, but concurrently increased the expression of pro-survival proteins Bcl-2 and p21 while decreasing the expression of tumor suppressor protein p53. Phosphorylation of Akt kinase and S6 pro-survival proteins were modulated in an alternating pattern with increasing concentrations of anethole. Studies were also conducted to investigate the effect of anethole on the sensitivity of MCF-7 cells to tamoxifen treatments. The effect of tamoxifen on cell proliferation was not affected significantly by co-treatment with anethole but importantly the suppression of cell survival by tamoxifen was enhanced when anethole is present at a concentration of 10-5 M. Preliminary data suggest that one mechanism by which anethole is mediating some of its suppressive effects is through modulation of ER activity, as measured by luciferase assays. Studies are on-going to evaluate the relevance of this modulation to the inhibitory effects of anethole on the MCF-7 cells, as well as the modulation of the signal transduction pathways indicated on survival.Conclusion: These data suggest that the anethole is a potential anti-tumor agent, and that co-treatment of tamoxifen and anethole is a potential approach to sensitize human breast MCF-7 cells to tamoxifen treatments.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3100.
Oncological Outcome and Patient's Satisfaction of Skin-Sparing Mastectomy and Immediate Breast Reconstruction: A Prospective Observational Study.
Authors: Anderson A. , Burgoyne G. , Mokbel K. 
Published: December 2010

Abstract
INTRODUCTION: The management of early breast cancer with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) is not based on evidence from randomised controlled trials. The purpose of this study is to evaluate the oncological safety, post-operative morbidity and patients' satisfaction with SSM and IBR using the latissimus dorsi (LD) myocutaneous flap and/or breast prosthesis. METHODS: One hundred and twenty five consecutive women underwent 137 SSMs with IBR (12 bilateral), using the LD flap plus implant (n=85) or implant alone (n=42), indications included breast cancer (n=130)and prophylaxis (n=7). Most tumours (99.2%) were Tis, T1, or T2 and only one tumour was T3 stage. Nipple reconstruction was performed in 69 patients, using a small local flap technique (n=61), nipple sharing (n=6), free skin graft (n=1) or Monocryl mesh (n=1). Thirty patients underwent contra-lateral surgery in order to optimise symmetry, including 19 augmentations and 11 mastopexy/reduction mammoplasties. Patient satisfaction with the outcome of surgery was assessed on a linear visual analogue scale ranging from 0 (not satisfied) to 10 (most satisfied). RESULTS: There was no local recurrence (LR) after a mean follow-up of 33.2 months (range=3-98 months). Overall survival was 99.2%, seven patients developed distant disease and one patient died of metastatic breast cancer. No case of partial or total LD flap loss was observed. Morbidities included infection, requiring implant removal in two patients and one patient developed marginal ischaemia of the skin envelope. Significant capsule formation, requiring capsulotomy, was observed in 87% of patients who had either PMR or prior RT compared with 13% for those who did not have RT. Eighty two (65.6%) of 125 patients completed the questionnaire with a median satisfaction scores of 9 (range=5-10). CONCLUSION: SSM with IBR is associated with low morbidity, high levels of patient satisfaction and is oncologically safe for T(is), T1 and T2 tumours without extensive skin involvement.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3113.
Adherence of Adjuvant Hormonal Therapies in Post-Menopausal Hormone Receptor Positive (HR+) Early Stage Breast Cancer: A Population Based Study from British Columbia.
Authors: Chan A. , Speers C. , O'Reilly S. , Pickering R. , Chia S. , Chia S. 
Published: December 2010

Abstract
Background: Adjuvant hormonal therapies for early-stage breast cancer significantly reduce the risk of recurrence, incidence of contralateral breast cancer and death from breast cancer. Optimal compliance to prescribed therapies is associated with improved patient outcomes. However, non-adherence to adjuvant tamoxifen and aromatase inhibitors (AIs) has been reported to range from 17-49% and 19-31% respectively.Objective: To evaluate medication adherence for a large population of post-menopausal women with HR+ early stage breast cancer that were prescribed initial adjuvant hormonal therapies in a publicly funded health care system, and to assess for predictive factors associated with higher rates of non-adherence.Methods: A retrospective cohort of post-menopausal patients diagnosed with HR+ stage I-III breast cancers referred to the BCCA between 2005-2008 whom were prescribed initial adjuvant hormonal therapies (either tamoxifen or an AI) were identified using the British Columbia (BC) Breast Cancer Outcomes Unit database. Cases were matched with the provincial BCCA pharmacy data repository to evaluate patterns of prescription filling. Factors including age, stage, tumor characteristics, use of chemotherapy, hormonal agent prescribed, and prescribing physician were pre-identified as potential factors predicting for non-adherence. Non-adherence was defined as less than 80% of days covered with a prescription.Results: A total of 4,592 patients were prescribed adjuvant hormonal therapies through the BCCA from 2005-2008. 2,414 patients were available for analysis after applying pre-defined inclusion criteria. Overall non-adherence rate was 40%, with non-adherence to tamoxifen and aromatase inhibitors at 42% and 37% respectively. The non-adherence cohort were older, had smaller tumor size, less nodal involvement, lower grade and lower rate of initial chemotherapy (all p&lt;0.001). Non-adherence rates specific to individual physician prescribers ranged from 16% to 67% (p&lt;0.001), and non-adherence rates between specialist provider groups were 34% among medical oncologists compared with 47% in radiation oncologists (p&lt;0.001).Conclusion: Overall non-adherence to adjuvant tamoxifen and AIs in this large population of postmenopausal women with HR+ positive early stage breast cancer was 40%. This likely represents a true reflection of both non-adherence and multiple factors associated with non-adherence given the population size, public health care setting and follow-up strategies. The non-adherent cohort may be the group that is most likely to benefit from hormonal therapy (lower tumor grade) and require hormonal therapy (less adjuvant chemotherapy). Future directions should include interventions directed at physicians in addition to patients given the discrepancy in non-adherence rates among prescribers.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 36.
CYP-2C19*2 Predicts Favorable Outcome of Tamoxifen Treatment for Advanced Breast Cancer.
Authors: Berns P. , Kok M. , Sweep F. , Look M. , Seynaeve C. , Lindemans J. , vantVeer L. , Span P. , Sleijfer S. , Foekens J. , Linn S. , van Schaik R. 
Published: December 2010

Abstract
Tamoxifen is metabolised by cytochrome P450 (CYP) enzymes to active metabolites. CYP2D6 and CYP2C19 genotypes have been reported to be associated with therapy outcome of adjuvant tamoxifen for breast cancer. Effects, however, were inconsistent and no data for advanced disease is available.We studied the association of functional polymorphisms in CYP2C19 and CYP2D6 with outcome of tamoxifen for advanced breast cancer.This multicenter study was performed on genomic DNA of 499 estrogen receptor (ER)-positive, retrospectively collected, primary breast tumor specimens of patients treated with first-line tamoxifen therapy for advanced disease.Primary endpoint was the time to treatment failure (TTF). Genomic DNA was analysed with Taqman allele-discrimination assays.A pooled analysis of three independent patient cohorts showed a longer TTF for CYP2C19*2 carriers, encoding lower enzymatic activity, compared to non-carriers (Hazard ratio (HR) (95% Confidence Interval (CI)): 0.71 (0.57-0.90), p=0.004). Neither the ultra-active CYP2C19*17 nor the inactive CYP2D6*4 allele were associated with TTF.In a pooled multivariable analysis, stratified for centre and time between primary diagnosis and occurrence of metastases, corrected for menopausal status at treatment start, adjuvant chemotherapy and CYP2D6*4 status, CYP2C19*2 was independently associated with TTF (HR (95% CI): 0.73 (0.58-0.91), p=0.007).CYP2D6*4 and CYP2C19*2 gene status were not prognostic for breast cancer outcome.In conclusion, CYP2C19*2 is associated with a longer time to treatment failure in breast cancer patients treated with tamoxifen for advanced disease.Our finding on the involvement of CYP2C19 in tamoxifen metabolism opens new avenues for further treatment individualisation and new management strategies.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4036.
Outcome Prediction in Node-Negative Breast Cancer Based on ASCO-Recommended Biomarkers uPA/PAI-1 Using the Final 10-Year Analysis of the Randomized Multicenter Chemo N0 Trial Compared to Adjuvant Online™.
Authors: Harbeck N. , Meisner C. , Ravdin P. , Kates R. , Friedel C. , Schmidt M. , Untch M. , Lisboa B. , Jaenicke F. , Schmitt M. , Thomssen C. ,   on Behalf of Chemo N0 Study Group
Published: December 2010

Abstract
Background: Based on interim analysis of Chemo N0, the first prospective multicenter randomized clinical trial using biomarkers uPA/PAI-1 for risk stratification and chemotherapy selection in N0 breast cancer, uPA/PAI-1 are now recommended for routine use by ASCO and AGO guidelines. Final 10-year follow-up of Chemo N0 has validated the clinically relevant long-term prognostic and predictive impact of uPA/PAI-1 in N0 breast cancer. To quantify the clinical utility of this impact, outcomes in subgroups defined by these biomarkers were compared to predictions of Adjuvant Online™, the leading validated tool based on established clinical factors. Methods: In Chemo N0, patients (n=647, 1993-98) were prospectively stratified according to uPA/PAI-1: High-risk patients were randomized (6x CMF vs. observation), low-risk patients observed. Retrospectively, we divided recruited patients into two groups (chemotherapy vs. no adjuvant therapy) and stratified using uPA/PAI-1 (low vs. high). Individual 10-year OS was calculated by www.adjuvantonline.org (Version 7.0); these estimated values were compared to the observed Chemo N0 10-year OS. Results: 383/647 patients have complete 10-year follow-up data. Median 10-year OS estimated by Adjuvant Online™ was 80.5% taking into account administered adjuvant therapy; 10-year Chemo N0 follow-up revealed observed 10-year OS of 74.7% (97/383 died). 77.8% (298/383) did not receive chemotherapy: In high-risk, untreated patients (n=137), 10-year OS was 72.3% vs. estimated 81.1%. In CMF-treated patients (all high-risk, n=85), observed OS was 61.2% vs. estimated 76.4%. Conclusions: For the first time, risk assessment by novel biomarkers is compared to that by Adjuvant Online™ in final data from a randomized prospective clinical trial. In patients with high uPA/PAI-1, the individual 10-year risk calculated by Adjuvant Online™ seems to be underestimated compared to observed patient outcome. Tumor-biological information provided by validated biomarkers thus has the potential of enhancing epidemiology-based risk estimation using only established factors.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4038.
Prognostic and Predictive Impact of Intrinsic Biological Classification by Immunohistochemistry (IHC) and QPCR for Adjuvant Tamoxifen in Pre-Menopausal Breast Cancer: Results from the NCIC CTG MA.12 Trial.
Authors: Chia S. , Ung K. , Bramwell V. , Tu D. , Perou C. , Ellis M. , Bernard P. , Vickery T. , Mardis E. , Cheang M. , Pritchard K. , Shepherd L. , Nielsen T. 
Published: December 2010

Abstract
Background: Aside from the estrogen receptor (ER), there is no other validated predictive biomarker for the magnitude of benefit from tamoxifen. Gene expression profiling has clearly demonstrated that breast cancer is a heterogeneous disease, and has re-classified breast cancer into intrinsic subtypes. We have utilized material from a prospective randomized trial of tamoxifen versus placebo in pre-menopausal women with primary breast cancer who have completed adjuvant chemotherapy (NCIC CTG MA.12 Trial) in order to evaluate the prognostic and predictive significance of intrinsic subtypes as classified by both IHC and qPCR.Methods: A tissue microarray (TMA) was constructed from 492/672 (72%) of the study population. A panel of six IHC antibodies (ER, PR, HER2, EGFR, CK 5/6 and Ki67) was utilized with established cut-offs to define the intrinsic subtypes of luminal A, luminal B, HER-2 and basal. Total RNA from 403/672 (60%) patients was sufficient for intrinsic subtyping with a 50 gene predictor (PAM50) by qPCR. In 354 cases intrinsic subtyping was performed by both methods.Results: There were no significant differences between the initial study population and the TMA series in baseline characteristics. Within the TMA series 39% (n=190) were classified as luminal A, 31% luminal B (n=143) [20% by Ki67 and 11% by HER2], 7% HER2-enriched and 17% basal-like by IHC. Intrinsic subtypes were prognostic with luminal A (5 year 93% OS) having the best outcome and basal-like (5 year 71% OS) the worst (p=0.0086 Wilcoxon). Tamoxifen appeared to benefit the luminal B cancers most (5 year DFS HR 0.67; 95% CI 0.39-1.16: p=0.077) when compared to placebo, however no subtype, nor ER status alone, predicted benefit of tamoxifen in this correlative study. Data for concordance for subtyping by IHC and qPCR as well as prognostic/predictive impact by qPCR subtyping will be presented.Conclusions: Intrinsic biological classification of breast cancer is important for prognosis and may have predictive value for relative benefit to tamoxifen. Further validation of these results are required.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4056.
High Frequency of BRCA1 Founder Mutations in the Bahamas.
Authors: Donenberg T. , Lunn J. , Turnquest T. , Curling D. , Krill-Jackson E. , Royer R. , Narod S. , Hurley J. 
Published: December 2010

Abstract
The frequency of mutations in the BRCA1 and BRCA2 genes differs among ethnic groups, due to regional founder effects. The Bahamas is an island nation of 305,000 people, with a complex history of immigration from the 1600s-1800s including English, Americans and African slaves. An initial survey by our group demonstrated that 48% of breast cancers in the Bahamas are diagnosed in women under 50 suggesting an inherited cause for many. In a follow up study, we identified four distinct BRCA1 mutations in 9 of 19 high risk Bahamian breast and ovarian cancer families (47.36%). A fifth mutation has been previously published in a Bahamian family and is a confirmed African founder mutation. In the current study, we sought to estimate the prevalence of these mutations among unselected breast and ovarian cancer patients from the Bahamas. We have enrolled 135 unrelated women with breast (n = 133) or ovarian cancer (n=2) attending public and private clinics in the Bahamas and Miami. A detailed family history was obtained from each patient and a saliva sample was obtained for DNA analysis. DNA samples were tested by mutation specific assay for the presence of five BRCA1 mutations (IVS13+1G&gt;A, M1775R, IVS16+6A&gt;C, 4730insG and 943ins10). Twenty-three mutations were detected, representing 17% mutation prevalence in this population, including IVS13+1G&gt;A (14 times), IVS16+6A&gt;C (two times), M1775R (three times), 4730insG (three times) and 943ins10 (once). This reflects a very high rate of genetic breast cancer in this population with a strong founder effect. This important finding raises the possibility of developing an inexpensive genetic screen for inherited susceptibility to breast cancer in the Bahamas and the need to mount an effective cancer prevention strategy for this population at high risk.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4078.