bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-14-11: Gene-expression analyses identify altered transcription factors and supports the antitumor activity of novel bromodomain inhibitors in triple negative breast cancer
Authors: Ocana A , Perez-Peña J , Serrano-Heras G , Corrales-Sanchez V , Montero JC , Gascón-Escribano MJ , Picazo MG , García-Olmo DC , Martin M , Pandiella A 
Published: May 2016

Abstract
Introduction: Identification of novel therapeutic targets in triple negative breast cancer (TNBC) is a main goal. In silico evaluation of human tumors by gene expression analyses can identify functions that could be pharmacologically inhibited. BET bromodomain inhibitors are a new family of compounds that reduce activity of oncogenic transcription factors through the inhibition of bromodomains.
Material and methods: We performed gene expression and functional analyses comparing triple negative tumors with normal breast samples. RT-PCR was used to evaluate genes down-regulated by treatment with the BET bromodomain inhibitors JQ1 and OTOX15 at different time points in MDA-MB231 cells. Cell proliferation and colony growth was measured by MTT uptake and 3D growth in matrigel in a panel of cell lines including HS578T, BT549, MDA-MB231 and HCC3153 treated with JQ1 and OTOX15. Evaluation of apoptosis and cell cycle was performed by flow cytometry using Annexin V and propidium iodide, respectively. Western-blot was used for evaluation of protein expression. Xenografted animals were used for the assessment of the in vivo activity of JQ1.
Results: Gene expression analyses identified upregulated genes including a number of transcription factors. These genes were more expressed in MDA-MB231 compared with MCF-10A. Treatment with JQ1 reduced the expression of some transcription factors at different time points. JQ1 and OTX015 reduced proliferation and cell growth in a panel of triple negative cell lines. They also led to arrest at the G0/G1 phase in HS578T and MDA-MB231 at 12 and 24 hours; that was confirmed by the biochemical evaluation of cell cycle mediators. An induction of apoptosis was observed at 48 hours in HS578T. JQ1 at 50 mg/kg daily reduced tumor growth in MDA-MB231 xenografted in nude mice.
Conclusion: Gene-expression profiling identified upregulated transcription factors in triple negative tumors compared with normal breast human samples. BET bromodomain inhibitors reduced the expression of some of these genes in cellular models. JQ1 shows clear antitumor activity in vitro and in vivo.
Citation Format: Ocana A, Perez-Peña J, Serrano-Heras G, Corrales-Sanchez V, Montero JC, Gascón-Escribano MJ, Picazo MG, García-Olmo DC, Martin M, Pandiella A. Gene-expression analyses identify altered transcription factors and supports the antitumor activity of novel bromodomain inhibitors in triple negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-14-11.
Abstract P4-01-04: Immunohistochemical and histological features of mammographic dense and non-dense tissue in breast cancer patients
Authors: dos Santos CC , Marshall P , Torresan R , Tinóis E , Duarte G , Teixeira S 
Published: May 2016

Abstract
Objective: We investigated immunohistochemical and histological composition of dense and non-dense breast tissue in 18 women undergoing mastectomy as the initial treatment for breast cancer. Materials and Methods: In each mammogram, we localized the dense and the non-dense areas. We used a localization technique based on a linear approximation method with interpolation of mammogram images and breast pictures. The selected areas were retrieved during mastectomy and analyzed. Results: Estrogen and progesterone receptors, Ki-67 and CD-34, were equally expressed in both tissues, as well as the percentage composition of fat. The percentage compositions of brownish spots among dense and non-dense tissues were significantly different (p = 0.0226). The number of terminal ductal lobular units was higher for dense than for non-dense breast tissues (p = 0.0019). In the non-dense breast tissue, there were no proliferative lesions with atypia, while we found flat epithelial atypia in 3 of the dense areas evaluated. Proliferative lesions without atypia and non-proliferative lesions were found in both tissues, but they were more frequent in dense than in non-dense breast tissues (23.5% vs 11.8%, p = 0.0455, and 17.6% vs 2.9%, p = 0.0253, respectively). Fibrosis was more frequently extensive or moderate in dense tissue, while it was predominantly mild in non-dense tissue (p = 0.03). Conclusion: There was no difference in the expression of the estrogen and progesterone receptors, Ki-67 and CD-34, in the dense and non-dense tissue areas in breast-cancer women. In addition, both stroma fibrosis and epithelial proliferation were responsible for higher mammographic density.
Citation Format: dos Santos CC, Marshall P, Torresan R, Tinóis E, Duarte G, Teixeira S. Immunohistochemical and histological features of mammographic dense and non-dense tissue in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-01-04.
Abstract P4-01-06: Microcalcifications as imaging biomarker in breast cancer: High-throughput radiogenomic analysis using microarrya data
Authors: Shin SU , Kim W , Song SE , Chu A , Han W , Moon WK 
Published: May 2016

Abstract
Purpose: To investigate relationships between microcalcifications and gene expression pattern using microarray analysis in breast cancer.
Materials and methods: The institutional review board approved this retrospective study and waived the informed consent. Clinicopathologic finding, mammographic features, and gene expression data were evaluated in 133 women (mean age, 50.1 years; range, 21-79 years) with stage I-III breast cancer. Women with microcalcifications (n=33) and without microcalcifications (n=100) were compared. Immunohistochemical analysis of estrogen receptor, progesterone receptor, HER-2, and Ki-67 expression was performed. Differentially expressed genes (DEGs) using Affymetrix GeneChip® Human Gene 2.0 ST arrays (53,427 probes) were identified in tissue with microcalcifications versus without microcalcifications. In addition, genes included in the prediction analysis of PAM50, MammaPrint® and OncotypeDX® were also compared between two groups (microcalcifications versus no calcification). To further investigate the functions and underlying biology of DEGs, we performed enrichment analysis using the Gene Ontology database and pathway anlyais using the Kyoto Encyclopedia of Genes and Genomes database and Ingenuity Pathway Analysis.
Results: Among clinicopathologic varibales, HER2 positivity (p&lt;0.001) and presence of comedo necrosis (p=0.024) are significantly higher in the calcification group. About 128 genes had differential expression (&gt; 1.5 fold difference, adjusted p value&lt;0.05). Among known gene signatures, GRB7 (fold change=2.26, p=0.006) and ERBB2 (fold change=2.13, p=0.001) which are known as associated with recurrence, cell invasion and poor survival were highly expressed. In contrast, ZNF385B which is associated with p53-mediated apoptosis and good prognosis was underexpressed (fold change=0.39, p=0.001) in calcification group. Significant gene ontology terms included response to wounding, coagulation, wound healing, and response to hypoxia. Network and canonical pathway analysis indicated that increased cellular movement, cellular growth and proliferation, cellular develoment, coagulation and atherosclerosis signaling in breast cancer with microcalcifications, suggesting biological aggressiveness.
Conclusion: Gene expression patterns are different according to microcalcifications status in breast cancer. Breast cancers with mammographic microcalcifications are associated with metabolic aggressiveness and poor prognosis.
Citation Format: Shin SU, Kim W, Song SE, Chu A, Han W, Moon WK. Microcalcifications as imaging biomarker in breast cancer: High-throughput radiogenomic analysis using microarrya data. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-01-06.
Abstract P4-03-02: Up-classification of suspicious breast masses using opto-acoustic imaging
Authors: Lavin PT , Stavros AT , Ulissey MJ 
Published: May 2016

Abstract
Purpose: Breast cancer diagnostic methodologies have been optimized to achieve increased sensitivity at the expense of relatively low specificity. Seno Medical's opto-acoustic (OA) imaging fuses real time co-registered, temporally interleaved laser optic and ultrasound imaging showing dual functional (hemoglobin de-oxygenation) and morphology findings for breast masses using a hand-held probe. We present data from the PIONEER Pilot study (n=100). We have shown improved specificity for OA relative to the ultrasound component (IUS) and the site determination by conventional diagnostic ultrasound (CDU). We now examine the BI-RADS upgrades for 36 malignant masses achieved by OA versus IUS and the site determinations using CDU.
Materials and Methods: A total of 7 independent registration readers (IRRs) blindly assessed all 36 malignant masses using IUS first and OA second without any knowledge of clinical data or outcome. Among the cancers, there were 2 BI-RADS 4b, 12 BI-RADS 4c, and 22 BI-RADS 5 according to participating site radiologists' CDU evaluations. IRRs trained to identify and score three OA internal features and two OA external features for all masses were immediately offered the results of two nomograms based on their OA feature scores to predict the Probability of Malignancy (POM), which was then used to assign a BI-RADS category.
Results: Combining data from all 7 readers, OA findings enabled upgrades of site CDU-determined BI-RADS categories 43% of the time for BI-RADS 4b and 29% for BI-RADS 4c; in contrast, the overall percentages of IUS upgrades versus site CDU were 21% for BI-RADS 4b and 10% for BI-RADS 4c. Overall, 12% of all OA reads resulted in upgrades in contrast to 4.4% for IUS compared to site CDU BI-RADS classifications. Relative to IUS, the overall percentages of OA upgrades were 58% for BI-RADS 4b and 34% for BI-RADS 4c. OA has comparable sensitivity to IUS.
Conclusions: OA was more likely than IUS to result in a BI-RADS upgrade of a malignant mass. If subsequently confirmed, OA findings may help identify more cancers prior to biopsy. The 2,095 PIONEER Pivotal Study will allow for confirmation.
Clinical Relevance: The ability to upgrade BI-RADS 4b and 4c for cancer masses is an unmet need. If verified, these findings could provide additional evidence to confirm a malignant mass earlier and spare subsequent diagnostic evaluations. This may help plan the efficient identification and excision of malignant masses.
Citation Format: Lavin PT, Stavros AT, Ulissey MJ. Up-classification of suspicious breast masses using opto-acoustic imaging. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-03-02.
Abstract P4-03-09: Malignant hyperechoic lesions in breast ultrasound - Frequency and characteristics
Authors: Camacho J , Horvath E , Pizzolon MF , Pinochet MA , Gallegos M , Galleguillos C , Uchida M , Cadiz F , Silva C 
Published: May 2016

Abstract
PURPOSE
Challenge current axiom regarding hyperechogenic lesions in breast US categorized as mainly benign lesions. 2) Present frequency of malignant hyperechoic lesions, describe their sonographic and histological characteristics.
METHOD AND MATERIALS
IRB approved retrospective review of 2369 consecutive US-guided Core biopsies between 2006 and 2014. Lesions were considered hyperechogenic when more than 90% of its volume had higher echogenicity than surrounding subcutaneous tissue. Variables assessed were: age, size, histology, mass or non-mass, margins, echogenicity, acoustic effect, orientation, location, presence of a hypoechoic center, vascularization and BI-RADS category. Qualitative variables were described by percentage distribution, mean and SD.
RESULTS
Thirty one (1,3%) lesions biopsied were hyperechoic: only 17 (54.8%) were benign. We found 14 patients (range, 39-81 years, mean 57,5 years) with hyperechoic cancers, accounting for 1,77% of all cancers. 12 (85,7%) were ductal and 2 (14,3%) lobular histology (mean 17,5 mm range 8-40mm). All of them exhibited a small central hypoechoic area and were partially or completely surrounded by fatty tissue. Shape, margins, orientation and vascular architecture were highly suggestive of malignancy at US, mammography and in MRI (BI-RADS 4B and 5). On histology, all lesions were surrounded by fatty tissue, with a low–cell count collagenous center with a higher peripheral cellularity, mixing and interweaving with adipose tissue.
CONCLUSION
Hyperechogenic breast cancers are rare (1.77%), and we challenge the current concept of high rate of benignity with a 45,2% of chances for malignancy. We propose that hyperechogenicity is given by interweaving bundles with adipose tissue, which provide higher amount of acoustic reflective surfaces, thus explaining its sonographic pattern.
CLINICAL RELEVANCE/APPLICATION
Hyperechogenic breast lesions should not be considered as always benign. Malignancy thresholds should not be influenced by this sonographic characteristic.
We propose histopathological explanation of this sonographic pattern.
Citation Format: Camacho J, Horvath E, Pizzolon MF, Pinochet MA, Gallegos M, Galleguillos C, Uchida M, Cadiz F, Silva C. Malignant hyperechoic lesions in breast ultrasound - Frequency and characteristics. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-03-09.
Abstract P4-07-08: The prognostic significance of ataxia-telangiectasia-mutated (ATM) and p53 expression in breast cancer
Authors: Suh KJ , Ryu HS , Lee K-H , Im S-A , Kim T-Y , Kim H , Yang Y , Moon H-G , Han S-W , Oh D-Y , Han W , Kim T-Y , Park IA , Noh D-Y , Bang Y-J 
Published: May 2016

Abstract
The purpose of this study was to investigate the correlation of ataxia-telangiectasia-mutated (ATM) protein and p53 expression with clinicopathological features and prognosis in patients with sporadic breast cancers. The expression of ATM and p53 was determined by immunohistochemistry in 420 surgically resected breast cancers. Loss of ATM was observed in 126 out of 407 evaluable cases (31.0%), and was significantly associated with aggressive features with large tumor size, lymph node metastasis, higher tumor grade, and negativity of ER and/or PR. ATM loss was associated with a significantly shorter disease-free survival (DFS) (p = 0.019). Abnormal p53 expression was found in 39.3% of tumors (157 out of 400), conferring a worse DFS as well (p = 0.002). When investigated together, combined ATM and p53 expression status were associated with a worse DFS (p = 0.002). On multivariate analysis, ATM loss and abnormal p53 expression status was an independent predictor of poorer DFS (intact ATM and normal p53 vs. ATM loss and abnormal p53, HR 3.350; 95% CI 1.496 - 7.502; p = 0.003). Furthermore, in patients treated with adjuvant anthracyclines, either p53 alone or p53 combined with ATM significantly influenced DFS (p = 0.004, p = 0.015, respectively). The present study demonstrates that expression of ATM and p53 is an independent prognostic marker in breast cancers, and might be a practical tool for predicting benefits from anthracycline-based adjuvant therapy.
Citation Format: Suh KJ, Ryu HS, Lee K-H, Im S-A, Kim T-Y, Kim H, Yang Y, Moon H-G, Han S-W, Oh D-Y, Han W, Kim T-Y, Park IA, Noh D-Y, Bang Y-J. The prognostic significance of ataxia-telangiectasia-mutated (ATM) and p53 expression in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-07-08.
Abstract P4-09-04: Robust 7-gene signature for recurrence prognosis of breast cancer validated in formalin-fixed paraffin-embedded samples
Authors: Chacolla RJ , Trevino VM , Scott SP , Guzman EA , Cardona S 
Published: May 2016

Abstract
BACKGROUND: Breast cancer (BC) is a heterogeneous disease with diverse biological-molecular characteristics and clinical behaviors. Traditionally, prediction of recurrence in patients recently diagnosed is a big challenge for oncologists. In the last decade, advances in gene expression profiling technologies have improved the genetic knowledge of breast cancer by reporting several prognostic gene-signatures. However, there is still a need for covering the molecular heterogeneity of this cancer. Integration of public microarray data could be used to identify better and robust predictive gene-signatures. The aim of this study was to investigate prognostic genes that might function as biomarkers to differentiate among all heterogeneous BC patients, into those with high, medium or low recurrence risk.
METHODS: We collected nine public datasets, 1574 BC patients with median follow-up time of 10 years. The data were split into train-test, 50% each. Train was subject to univariate and multivariate analysis to generate a signature, which was validated in the test data. Seven genes were identified with high accuracy for recurrence prediction. This signature was validated in 40 formalin-fixed paraffin-embedded (FFPE) Mexican BC tissues with clinical follow up of 3 to 13 years by quantitative RT-PCR assays.
RESULTS: We identified a 7-gene signature which showed an accuracy prediction measured by concordance index of 65.62% and Log-rank test p-value: 1 x 10-15. The validation of the gene-signature level expression in 40 FFPE samples in Kaplan Meier analysis showed prediction significance by concordance index of 65.25% and Log-Rank p-value: 0.0005.
CONCLUSIONS: This 7-gene signature may provide a powerful tool to guide the adequate treatment protocols in early-diagnosed breast cancer patients.
Citation Format: Chacolla RJ, Trevino VM, Scott SP, Guzman EA, Cardona S. Robust 7-gene signature for recurrence prognosis of breast cancer validated in formalin-fixed paraffin-embedded samples. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-04.
Abstract P4-09-05: Expression of breast cancer stem cell marker as a predictor of prognosis and response to trastuzumab in HER2-positive breast cancer
Authors: Seo AN , Lee HJ , Kim EJ , Jang MH , Kim YJ , Kim JH , Kim S-W , Ryu HS , Park IA , Im S-A , Gong G , Jung KH , Park SY 
Published: May 2016

Abstract
BACKGROUND: Breast cancer stem cells (BCSCs) have been suggested to have clinical implications for cancer therapeutics because of its proposed role in chemoresistance. The aim of this study was to investigate the impact of BCSC marker expression in clinical outcome and trastuzumab response HER2-postive breast cancer.
METHODS: We analyzed the clinical significance of BCSC marker (ALDH1 and CD44+/CD24-) expression in 242 HER2-positive primary breast cancers using immunohistochemistry. In addition, we examined the relationship between BCSC marker expression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab.
RESULTS: In the first set, ALDH1 positivity and CD44+/CD24- phenotype were detected in 10.0% and 29.9%, respectively. ALDH1 positivity and CD44+/CD24- phenotype correlated with hormone receptor negativity. In survival analyses, CD44+/CD24- phenotype, but not ALDH-1 expression, was found to be an independent prognostic factor for poor disease-free and overall survival of patients in entire group, and in subgroup not receiving trastuzumab. In HER2-positive primary breast cancer patients treated by adjuvant trastuzumab, CD44+/CD24- phenotype was also an independent poor prognostic factor for disease-free survival. However, ALDH1 positivity and CD44+/CD24- phenotype had no effect on trastuzumab response and survival in patients with metastatic HER2 positive breast cancer.
CONCLUSION: These results suggest that CD44+/CD24- phenotype can be used as a prognostic factor for clinical outcome and a predictive factor of trastuzumab response in patients with HER2-positive primary breast cancer.
Citation Format: Seo AN, Lee HJ, Kim EJ, Jang MH, Kim YJ, Kim JH, Kim S-W, Ryu HS, Park IA, Im S-A, Gong G, Jung KH, Park SY. Expression of breast cancer stem cell marker as a predictor of prognosis and response to trastuzumab in HER2-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-05.
Abstract P4-09-19: Comprehensive multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast
Authors: Gatalica Z , Vranic S , Ghazalpour A , Xiu J , Ocal I , McGill J , Bender R , Discianno E , Sanati S , Reddy S , Pockaj B 
Published: May 2016

Abstract
Introduction: Malignant phyllodes tumors are rare breast malignancies (0.1% of all breast tumors) with limited effective treatment options for recurrent and metastatic disease. Recent trials indicated a potential for anti-angiogenic therapy in soft tissue sarcomas, which led us to investigate these pathways.
Materials and Methods: Thirty-five malignant phyllodes tumors (including two cases with matched primary and metastatic tumors) were profiled using gene sequencing (Next-generation and Sanger), gene copy number analysis (in-situ hybridization), whole genome RNA expression, and protein expression (immunohistochemical assay).
Results: RNA microarray assay showed consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin2, VCAM1, PDGFRA, PTTG1, and CYP3A5 in all cases analyzed (n=5). No mutations in KDR (VEGFR2) were detected (0/26). EGFR protein overexpression was observed in 25/26 (96%) of cases with amplification of the EGFR gene in 8 cases (33%). EGFR gene mutations were identified in 2 cases (8%) including one case with presumed pathogenic V774M mutation and one case with EGFRvIII mutation. The most common mutations included those of TP53 (50%) and PIK3CA (15%) while other mutations (BRCA1, BRCA2, RET, CDH1, MLH1, ATM) were rare affecting single phyllodes cases. Two cases with matched primary and metastatic cancers harbored the same mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively).
Conclusions: Comprehensive multiplatform profiling approach to phyllodes tumors identifies various molecular alterations of which some are potentially actionable. Our data suggests that anti-angiogenic therapy may also be effective in patients with malignant phyllodes tumor. Evaluation of EGFR pathway discovered consistent protein over-expression but rare activating mutations, which necessitates refinement in patient selection targeting these pathways.
Citation Format: Gatalica Z, Vranic S, Ghazalpour A, Xiu J, Ocal I, McGill J, Bender R, Discianno E, Sanati S, Reddy S, Pockaj B. Comprehensive multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-19.