bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between Histopathological Diagnosis and Real-Time Tissue Elastography Scores.
Authors: Nishiyama Y. , Sakaguchi U. , Matsushita K. , Kawagoe A. 
Published: December 2010

Abstract
Background“Hardness” is important characteristics of carcinoma. Recent invention of Real-time Tissue Elastography (EG) has made scaling the hardness possible. At 31st SABCS, we reported that B-mode ultrasound(US)+mammography(MMG)+EG demonstrated high sensitivity even for the malignancy of the mass-forming lesions of 1.1 cm or smaller in diameter. This results suggested that possibility of a mass-forming lesion being malignant is ignorable low when it is judged as “not malignant” by this combined method. In this study, we verified correlation between EG score and histopathological diagnosis.Method416 patients with mass-forming and non-mass-forming breast lesions (118 malignant, 298 benign) whose tissues were diagnosed by histopathologically from October 2007 to March 2009 were studied. The hardness was scored on a scale 1 to 5 on Tsukuba elasticity scoring system.ResultsIn mass-forming breast lesions, the mean overall score of malignant diseases was 4.1 (invasive carcinoma 4.3, noninvasive carcinoma 3.5), and the mean overall score of benign diseases was 2.4, and thus scores of malignant diseases were significantly high (&lt; 0.0001). On the other hand, in non-mass-forming breast lesions, the mean overall score of malignant diseases was 2.3 (invasive carcinoma 2.5, noninvasive carcinoma 2.4), and the mean overall score of benign diseases was 2.0, and thus no differences were seen between them. Furthermore, for examination by mass-forming lesions combined with non-mass-forming lesions the mean score of noninvasive carcinomas was 2.5.ConclusionIt was found that in mass-forming lesions, high scores suggest invasive carcinoma and low scores suggest benign diseases. However, as in non-mass-forming lesions, both invasive and noninvasive carcinomas almost show no high EG scores, it appeared necessary to look into invasive examinations such as biopsy for the diagnosis of non-mass-forming lesions.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5026.
MDCT Is Very Useful for Evaluating the Spread of DCIS.
Authors: Takayanagi H. , Kimijima I. , Yoshida K. 
Published: December 2010

Abstract
Introduction: Ductal carcinoma in situ (DCIS) may occasionally spread widely in the duct-lobular segment, thereby complicating the complete resection of the lesion in breast-conserving surgery. In order to perform a safe operation for DCIS, the lesion area must be precisely evaluated in the preoperative imaging studies. We performed multidetector-row computed tomography (MDCT) for patients with DCIS and investigated the potential of MDCT for detecting DCIS lesions.Patients and methods: A total of 74 patients with DCIS underwent MDCT. The size of the DCIS lesion in each patient was measured in the volume-rendering view, and these sizes were compared with the lesion sizes obtained by mapping from the pathological tests. The differences between the lengths obtained from pathological tests and those obtained from MDCT (L-path-L-CT) were calculated, and the relationships between the differences and some factors were investigated.Results: Among the 74 DCIS patients who underwent MDCT, DCIS was detected in 61 patients (82.4%). Among these 61 cases, 45.8% were cases of comedo-type DCIS, but the detection rates for comedo and noncomedo cases were not different. The L-path-L-CT values for histological grade I DCIS (1.55 cm) and grade II & III DCIS (0.23 cm) were statistically different. Higher-grade DCIS was more detectable than low-grade DCIS (p = 0.013). Among the other factors, the MDCT assessments and the pathological assessments for comedo-type DCIS and Her-2-positive cases were more consistent than the corresponding results for noncomedo DCIS and Her-2-negative cases. However, these differences were not significant.Conclusion: MDCT shows high efficiency in detecting DCIS. More aggressive types of DCIS, such as higher grade, comedo type, and Her-2-positive DCIS were more precisely detected by MDCT. In comparison with magnetic resonance imaging (MRI), the patient's position during MDCT testing is more similar to that during surgery. Therefore, MDCT is a highly useful presurgical imaging technique for the assessment of DCIS.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5029.
A Randomized Controlled Multicenter Trial of a Nutritional Formula in Women with Mastalgia Associated with Fibrocystic Breast Changes.
Authors: Mansel R. , Voss A. , Seth A. , Rushlow K. 
Published: December 2010

Abstract
Objective: Nodularity is a problem for clinical and radiological evaluation of the breast. A randomized, controlled, double-blinded trial was performed in women with cyclic breast pain (mastalgia) associated with fibrocystic breast changes to determine the effect of a liquid nutritional formula on breast pain and nodularity.Study Design: Following a one month baseline assessment, women were randomly assigned to receive 4 ounces per day of an experimental (EXP) or control liquid nutritional formula (CONT) for three months. The EXP contained 1 gram of gamma linolenic acid (GLA) (as borage oil), 750 mcg of iodine (as potassium iodide), and 70 mcg of selenium (as sodium selenate). The CONT was an isonitrogenous, isocaloric formula prepared with high-oleic safflower oil in place of borage oil, and without additional GLA, iodine, or selenium. Women were asked to record breast pain, supplemental medications, and menstrual signs daily using an interactive voice-response system (IVRS). Physical breast exams were performed by a healthcare professional at baseline and at the end of the study for a determination of nodularity.Results: A total of 503 women were screened for eligibility from 21 centers distributed across the United States. From this group, 188 women were randomized to receive the EXP or CONT intervention. The groups were similar at baseline. Peak breast pain scores were reduced from baseline similarly in the EXP (-32.2%) and CONT (-33.1%) groups (p=0.64). Among women who continued to take non-prescription pain medication for management of breast pain, the amount of medication was significantly less in the EXP group (p=0.0143). In addition, there was a greater reduction in breast nodularity in women taking the EXP compared to the CONT (p=0.03 vs. p=0.64). Both groups reported similar average weight at baseline, but women in the EXP lost an average of 2.6 lbs. of body weight, while those in the CONT gained an average of 3.6 lbs by the end of the study. Both formulas were well tolerated and willingness to consume the nutritional intervention was 82.7% in the CONT and 90.4% in the EXP as calculated by the number of voluntary withdrawals from the study and discontinuation of treatment for any reason. Women were considered compliant if the consumed at least 70% of the study product (daily reported by IVRS).Conclusion: These results indicate that the daily liquid nutritional formula containing GLA, iodine, and selenium may provide a safe nutritional alternative for reducing both nodularity and nonprescription medication use associated with cyclic breast pain in women with fibrocystic breast changes. Reduction in nodularity may improve physician and mammographic evaluation of the breast.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5034.
A Multicenter Randomized Phase II Study of Sequential Epirubicin/Cyclophosphamide Followed by Docetaxel with or without Celecoxib or Trastuzumab According to HER2 Status, as Primary Chemotherapy for Localized Invasive Breast Cancer Patient.
Authors: Pierga J. , Delaloge S. , Giacchetti S. , Brain E. , Savignoni A. , Sigal-Zafrani B. , Mathieu M. , Bertheau P. , Guinebretière J. , De Cremoux P. , Spyratos F. , Marty M. 
Published: December 2010

Abstract
Purpose: To assess anti tumor activity of sequential epirubicin/cyclophosphamide followed by docetaxel with the randomized addition of celecoxib In Her2-ve patients or trastuzumab in Her2+ve patients versus no additional treatment, in terms of pathological complete response (pCR), defined as absence of residual invasive breast carcinoma and of nodal involvement.Patients and methods: 340 patients with stage II and III breast adenocarcinoma, with tumors ineligible for breast conservative surgery received 8 sequential 3 weekly cycles with epirubicin (75mg/m2)-cyclophosphamide (750mg/m2) for 4 cycles followed by docetaxel (100 mg/m2) for 4 cycles. According to HER2 status (IHC + FISH) they were randomized to receive together with docetaxel, in HER2 negative group (220 patients) celecoxib 800 mg/day during cycles 5-8 or no additional treatment and in HER2 positive group (120 patients) trastuzumab (8mg/kg then 6mg/kg) infused together with docetaxel or no additional treatment. All patients except eight with HER2+ tumor received adjuvant trastuzumab for a cumulative duration of 12 months.Results: In the HER2 negative group, pCR (grade 1 and 2 of Chevallier's classification) was observed in 11.5% and 13% of patients treated without and with neoadjuvant Celecoxib respectively. In the HER2+ group, pCR rate reached 26% in those having received neoadjuvant trastuzumab versus 19% in the others. There was no cardiac toxicity and no toxic death. Triple negative breast cancers experience the highest pCR rate of 30%.Conclusion: It is the first report on the effect of the addition of celecoxib to chemotherapy in neoadjuvant setting in breast cancer, showing that celecoxib does not improve the pCR rate. Addition of trastuzumab does, yet not to the extent reported with a protracted co-administration before surgery. Expression of hormonal receptors appears to be the major prognosticator for pCR. Molecular studies of gene expression profiling should allow improving such prediction.Supported by PHRC AOM/2OO2/02117, Pfizer inc., Roche, sanofi-aventis.ISRCTN10059974
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5054.
High Resolution Oligonucleotide Array-CGH and Hot Spot Mutations To Select Patients for Targeted Therapies.
Authors: De La Cruz J. , Scott V. , Richon C. , Job B. , Dessen P. , Mathieu M. , Delaloge S. , Soria J. , Campone M. , Dalenc F. , Bachelot T. , Lazar V. , Andre F. 
Published: December 2010

Abstract
Background. A high number of genomic alterations (gene amplification, mutations) have been reported in breast cancers, and could potentially be targeted in early clinical trials. In the present molecular screening program, we aim at performing CGH array and hot spot mutations for 200 patients with metastatic breast cancer, in order to drive these patients in specific early clinical trials.Patients and Methods. Patients were selected to present a metastatic breast cancer under treatment in four French Centers. DNA was extracted by Qiagen method from either primary breast cancer or metastatic lesions. The hybridizations were done on 4*44K Agilent Array CGH. The analysis was done with Analytics v3.4.40 software. The file reported amplified zones (log2ratio&gt;0.84 for biopsy, 1.58 for FNA) and focused on predefined genes that encode a candidate target. Hot spot mutations cover PI3K, AKT, PTEN genes. The primary endpoint was to determine how many patients were driven to a specific clinical trial because of molecular analyses. The secondary endpoints included PFS and response rates.Results. As june 12th, 109 patients were included in the molecular screening program. CGH array was feasible and could be interpreted within one month in 85 (78%) patients. Array-CGH identified high level amplification in 57 patients (67%). As expected, the two most frequent amplicons included ERBB2 (17q11-12, 24%) and FGFR1 (8p11, 16%).The accuracy to detect ERBB2 amplification was 90%. A significant number of patients presented rare gene amplifications including ERBB4 amplification (n=1), CCND1/FGF4 amplification (n=6), FGFR2 (n=2), EGFR (n=1), VEGFB (n=4), BCR (n=1)Interestingly, only 4 patients presented TOP2A amplification. Hot spot mutations for PI3KCA, AKT, PTEN is being performedConclusion. This preliminary analysis shows that array CGH allows to identify patients who are candidate for targeted agents in phase I/II trials. Accrual will continue until 200 patients. Selected patients will be included in clinical trials in second semester of 2009 after a target validation by IHC.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5067.
Brk/PTK6 & Bcl-x Proteins Contribute to Reduced Sensitivity to Chemotherapy.
Authors: Burmi R. , Pennington C. , Edwards D. , Harvey A. 
Published: December 2010

Abstract
Background: Brk/PTK6 is an intracellular protein tyrosine kinase which is frequently overexpressed in the majority of breast cancers and has been shown to increase the anchorage-independent survival of breast cancer cell lines by altering Bcl-xL:Bcl-xS ratios. A Brk binding partner has also been found to modulate the alternative splicing of the Bcl-x gene, and altered Bcl-xL/xS levels are implicated in cell sensitivity to chemotherapeutic agents. We hypothesised that Brk may decrease cell response to chemotherapy through regulation of Bcl-x.Materials & Methods: To determine the clinical relevance and coexpression of Brk and Bcl-xL/S, quantitative PCR was performed on a clinical breast cancer biopsy material (n= 46). Gene knockdown studies using siRNA for either Brk or Bcl-xL were performed in T47D breast cancer cell line. Cells were subsequently cultured onto a 96 well plate in quadruplicate and subject to dose range of the chemotherapeutic drug, doxorubicin or paclitaxel for 72 hours before being tested for viability using the MTT assay. Protein levels for Brk, Bcl-xL/xS in response to siRNA treatments were determined using western blotting.Results: Quantitative PCR analysis of clinical breast cancer series reveal that Bcl-xL and Bcl-xS expression were associated with high grade tumours (p=0.028 and p=0.009 respectively). Moreover, both Bcl-xL and Bcl-xS were found to be significantly associated with Brk expression within these clinical samples (p&lt;0.0001 and p=0.0026 respectively). T47D breast cancer cells with suppressed Brk levels showed a significant increase in sensitivity to doxorubicin and paclitaxel compared to control cultures (p=0.035 for doxorubicin and p&lt;0.05 for paclitaxel at 0.625μM and 0.25nM respectively). Reduced Brk levels in T47D cells resulted in reduced levels of Bcl-xL protein. T47D cells with suppressed Bcl-xL levels also showed a significant increase in the sensitivity to doxorubicin compared to control cultures (p=0.039 at 0.31μM).Conclusion: These data suggests that Brk expression decreases the sensitivity of currently used chemotherapies through a mechanism that may involve regulation of Bcl-xL/xS protein levels. Thus targeting Brk may represent an important strategy for improving patient responses to chemotherapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5068.
A TCRMimic Monoclonal Antibody Generated from a Directly Discovered Epitope of p68 RNA Helicase Dramatically Debulks Large Established Tumors through Recognition of a Specific MHC/Peptide Complex.
Authors: Verma B. , Weidanz J. , Weidanz J. 
Published: December 2010

Abstract
Debulking large tumors using monoclonal antibodies (mAb) that specifically recognize unique T cell epitopes represents a novel approach to cancer therapy.Using a mAb designated as a TCRm we recently demonstrated the in vivo suppression of tumor growth. The TCRm had specificity for a peptide/MHC class I molecule expressed on the surface of the tumor cells. In this study we use an innovative direct epitope discovery strategy that led to the identification of peptide YLLPAIVHI in the context of HLA-A*0201 (YLL/A2) in human breast carcinoma cell lines. The peptide is derived from the DEAD Box RNA helicase protein p68, a protein overexpressed and highly phosphorylated in malignant cells. A TCRm antibody (RL6A) was generated and characterized for binding specificity, sensitivity and affinity for the YLL/A2 target. The TCRm specifically stained cells that co-expressed HLA-A2 and p68 but not cells lacking expression of p68 protein or HLA-A2 alone. It binds to cognate peptide/HLA-A2 with an affinity constant (KD) of 5.69 x 10-10 M and recognized specifically the YLL/A2 epitope in human breast cancer tissue but not in normal control breast tissue.Mice implanted in the mammary fat pad with human breast tumor cells grew tumors of considerable size, yet when treated with RL6A TCRm there was a marked reduction in tumor size. Examination of frozen tumor tissue sections revealed significantly greater numbers of apoptotic cells in mice treated with RL6A TCRm than with control antibody. Investigation in vitro showed that TCRm engagement of specific YLL/A2 epitope led to the induction of apoptosis providing the first experimental evidence that MHC signaling could directly mediate tumor cell death. Together, these data indicate that TCRm targeting of specific peptide/MHC complexes unique to tumor cells is effective not only in slowing the growth of tumors but also in dramatically reducing the size of established tumors and suggests a possible novel approach to the treatment of cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5072.
Combination of a Novel Growth Hormone Releasing Hormone Antagonist JMR 132 and Tamoxifen Enhances the Inhibitory Effects on Growth of ZR 75 and T47D Estrogen Dependent Human Breast Cancer Cells In Vitro and In Vivo.
Authors: Buchholz S. , Koester F. , Schally A. , Krishan A. , Papadia A. , Ortmann O. , Seitz S. 
Published: December 2010

Abstract
Background: Tamoxifen is the oldest selective estrogen receptor modulator (SERM) developed to antagonize the estrogen receptor function on human breast cancer cells. JMR 132 is a novel GHRH Antagonist proven to be potent inhibitor of tumor growth in estrogen receptor negative human breast cancer cell lines. A combination of both substances could induce a more potent growth inhibition, as compared to the single drugs.Methods: To determine inhibitory effects of the GHRH antagonist JMR 132 and Tamoxifen alone and in combination, estrogen receptor positive cell lines ZR 75 and T 47D were incubated with substances at concentrations of 2.5µM, 5µM and 10µM. The cell viability after a period of 72 h was measured by MTT assay. To assess if the treatment arrested cell growth at a specific phase of the cell cycle or simply caused cell death, we performed a flow cytometric DNA cell cycle analysis on ZR 75 cells exposed to JMR 132, Tamoxifen and their combination. In an in vivo model, the cell line ZR 75 was xenografted subcutaneously into nude mice. Treatment groups were control, JMR 132 at a dose of 10µM, Tamoxifen at a dose of 100µgr per mouse q3 per week and the combination of both substances. All given for a period of 4 weeks.Results: In vitro 1o µM JMR 132 and Tamoxifen significantly decreased the proliferation of the ZR 75 and T47D cell lines, as compared to controls (p&lt; 0.05). The combination of 1o µM inhibited the growth of ZR 75 was significantly by 14%, as compared to JMR 132 alone. The combination also significantly suppressed the growth of T47D by 14% and 22% respectively, as compared to Tamoxifen and JMR 132. In in vivo treatment with the combination of JMR 132 and Tamoxifen induced a significant inhibition of tumor growth of ZR 75 xenografts after 14 days compared to the single agents groups and inhibition remained significant until the end of the study on day 28. The flow cytometric DNA cell cycle analysis revealed a cell cycle arrest in the S Phase which led to apoptosis of the cells.Conclusion: Treatment of ZR 75 and T47D estrogen receptor positive human breast cancer lines with GHRH antagonist JMR 132 and its combination with Tamoxifen induced potent inhibitory effects in vitro and in vivo and led to subsequent cell death. Further studies are being conducted to elucidate the mechanisms of action of these effects.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5073.
An Evaluation of the Safety and Efficacy of Lapatinib Plus Trastuzumab Plus Paclitaxel in First-Line HER2+ Metastatic Breast Cancer.
Authors: Esteva F. , Franco S. , Hagan M. , Somer R. , Dombroski C. , Florance A. , Turner S. , Stein S. , Perez A. 
Published: December 2010

Abstract
Background: Trastuzumab given concomitantly with paclitaxel is an established first-line metastatic breast cancer (MBC) treatment; however, approximately 30% to 40% of patients show no response as defined by RECIST to this combination. Lapatinib is an oral dual tyrosine kinase inhibitor of EGFR and HER2 and approved, in combination with capecitabine, after trastuzumab-based therapy for HER2+ MBC. The differing mechanisms of action may allow synergy between lapatinib and trastuzumab when given concurrently with paclitaxel for MBC.Methods: This is an open-label phase I safety study. The primary objective of the study was to assess the safety and tolerability of lapatinib when administered with concurrent paclitaxel and trastuzumab. Patients were enrolled into 1 of 3 cohorts. Cohort 1 received lapatinib (1000 mg/d), paclitaxel (80 mg/m2 weekly for 3 weeks of a 4-week cycle), and the standard weekly dose of trastuzumab. Cohort 2 received lapatinib (1000 mg/d), paclitaxel (70 mg/m2), and trastuzumab. Cohort 3 received lapatinib (750 mg/d), paclitaxel (80 mg/m2), and trastuzumab. Patients: were 3+ by IHC or FISH amplified for HER2; had not received prior treatment in the metastatic setting; and had an ECOG performance status of 0 or 1. Safety was assessed weekly and tumor response per RECIST every 8 weeks. Treatment continued until disease progression or toxicity. All patients received prophylactic loperamide per protocol amendment.Results: Open-label safety enrollment is complete and preliminary safety data are available for all 63 patients. The most frequently reported AEs for all cohorts were diarrhea (81%), fatigue (71%), rash (68%), nausea (59%), alopecia (56%), and vomiting (37%). Dehydration was the most frequently reported serious AE (SAE) (n=6; 10%) and most were in cohort 1 (5 patients). Diarrhea of any grade was reported for 97% of patients in cohort 1, 93% of patients in cohort 2, and 50% of patients in cohort 3. No grade 4 or 5 diarrhea events were reported. The proportion of patients with a maximum toxicity of grade 3 diarrhea was 62% in cohort 1, 43% in cohort 2, and 20% in cohort 3. Two patients (both in cohort 1) reported diarrhea as a serious AE and a total of 4 patients (6%) had lapatinib withdrawn due to diarrhea (none in cohort 3).Conclusions: Preliminary safety results show a high incidence of grade 3 diarrhea when lapatinib was given at a dose of 1000 mg/d concurrently with paclitaxel and trastuzumab. This incidence was significantly reduced with a lapatinib dose of 750 mg/d in combination with paclitaxel and trastuzumab when given with loperamide. Final safety and efficacy data, including overall response and progression-free survival, from this open-label safety study will be presented.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5085.