bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-02-04: Plasma autoantibodies associated with basal-like breast cancers
Authors: Wang (Student) J , Figueroa JD , Wallstrom G , Barker K , Park JG , Demirkan G , Lissowska J , Anderson K , Qiu J , LaBaer J 
Published: May 2016

Abstract
Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease.
Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case-control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed.
Results: We identified a 13-AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (p=0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival (MN1 AAb marker HR=2.25 95%CI= 1.03-4.91 p=0.04; TP53, HR=2.02, 95%CI 1.06-3.85, p=0.03). We found limited evidence that AAb levels differed by demographic characteristics.
Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection. Currently, they are also being tested in a large national blind validation trial using a well characterized independent sample set.
Citation Format: Wang (Student) J, Figueroa JD, Wallstrom G, Barker K, Park JG, Demirkan G, Lissowska J, Anderson K, Qiu J, LaBaer J. Plasma autoantibodies associated with basal-like breast cancers. [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 P5-02-04.
Abstract P5-02-07: Effect of multidisciplinary case conferences on physician decision making: Breast diagnostic rounds
Authors: Foster T , Bouchard-Fortier A , Olivotto I , Quan ML 
Published: May 2016

Abstract
Background: Participation in multidisciplinary case conferences (MCCs) continues to be highly variable, in spite of proven benefits. One contention is the lack of perceived utility on patient management.
Purpose: To evaluate the utility of MCCs on physician decision making in benign and malignant breast disease management.
Methods: At the Foothills Medical Centre, diagnostic breast MCCs occur biweekly. Patients with interesting or challenging diagnostic or management issues were discussed by attending surgeons, radiologists, pathologists, nurse coordinators and oncologists. Prior to case discussion, the presenting physician was asked to specify his/her management plan. Their response was recorded and compared to the management plan consensus after the MCC discussion. For each case a clinical summary and question was provided by the presenting physician, followed by a review of diagnostic images and/or pathology. After group discussion, a management consensus was achieved and documented. A management change was defined as a difference compared to the pre-MCC plan or if there was no definite management plan prior to MCC.
Results: From November 5th, 2014 to May 6th, 2015, 52 patients were discussed in 11 MCCs (1 to 8 patients per MCC). No MCCs were cancelled due to insufficient patients. Of these, 23 (44%) had a change in the management plan compared to the pre-MCC intent including 7 cases where there was no clear plan prior to MCC. Among the 23 cases with a management change, 12 (52%) were due to new or clarified information from radiology review, 6 (26%) were due to new or clarified details from pathology review and 5 (22%) changes occurred from both radiology and pathology review. All cases presented resulted in a consensus management recommendation.
Conclusion: The MCCs had a substantial impact on physician decision making. Nearly half of cases presented resulted in a change in clinical recommendation, the majority of which were based on new/clarified diagnostic imaging or pathology information. Presentation of cases at MCCs should be encouraged given their clinical impact on patient care, especially for challenging diagnostic or management issues.
Citation Format: Foster T, Bouchard-Fortier A, Olivotto I, Quan ML. Effect of multidisciplinary case conferences on physician decision making: Breast diagnostic rounds. [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 P5-02-07.
Abstract P5-03-05: Genomic analysis and efficacy of entinostat in basal-like and HER2-overexpressing models
Authors: Tanioka M , Usary J , Darr DB , Harrell CJ , Perou CM 
Published: May 2016

Abstract
Background. The histone deacetylase inhibitor Entinostat has been under development for patients with metastatic estrogen receptor-positive breast cancer, and its use in Basal-like and HER2-overexpressing breast cancer has been limited. Here we provide results of a study using cell-lines and genetically engineered mouse (GEM) models of breast cancer to examine the effects of Entinostat and combination therapies on multiple in vitro and in vivo models.
Methods. Breast cancer cell lines SKBR3, BT474 and MCF-7 were treated with or without Entinostat at their IC50 doses and their gene expression profiles determined. Two breast cancer GEM models (MMTV-neu and C3-Tag) were used to test the efficacy of Entinostat alone, or in combination with cyclophosphamide, or a murine version of an anti-mouse PD1 immune checkpoint inhibitor.
Results: Entinostat was an effective in vitro drug with IC50 ranging from 700 to 1500 nM. Supervised analysis of gene expression data coming from treated cell lines showed induction of multiple major histocompatibility complex (MHC) class I/II genes on 6p21. In addition, several MHC genes were also upregulated in C3-Tag treated by Entinostat; because of these findings, the GEM models are currently being treated with the combination of Entinostat and the anti-mouse PD-1 inhibitor. In vivo, GEM tumors treated only with Entinostat were observed to have high objective response rates of 88% and 33% in MMTV-Neu and C3-Tag, respectively. The combination with cyclophosphamide provided significant improvements in the C3-Tag mice over either agent alone, with 11 of 17 mice achieving a CR or PR, and an extension of overall survival (98 days vs 33 days); Entinostat (42d, p=0.002) and Cytoxan (47d, p=0.001).
Conclusions. Entinostat showed anti-tumor activity in vitro and in vivo, and was synergistic with cyclophosphamide in the Basal-like C3-Tag mouse model. The upregulation of MHC genes induced by Entinostat at RNA level suggested the interaction with immune response, which is currently under study and will be presented.
Citation Format: Tanioka M, Usary J, Darr DB, Harrell CJ, Perou CM. Genomic analysis and efficacy of entinostat in basal-like and HER2-overexpressing models. [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 P5-03-05.
Abstract P5-03-12: Selenocystine inhibits triple-negative breast cancer cell proliferation by inducing cell apoptosis and S-phase arrest
Authors: Long M , Qiu W , Wu J , Liu R , Su H 
Published: May 2016

Abstract
Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited effective treatment options. New therapeutic approaches are urgently needed to improve the prognosis of TNBC. Reactive oxygen species (ROS) are inherent byproducts of oxidative metabolism, and forced stimulation of glucose oxidation in cancer cells raises oxidative stress and sensitizes cells to different stresses. Therefore, targeting the antioxidant capacity of cancer cells has become a promising anticancer strategy. As a redox modulator, selenocystine (SeC) has received a great deal of attention and has been shown effective against human melanoma, hormone receptor-positive breast cancer, and cancers of liver, lung and cervical in vitro. However, whether SeC exerts an anticancer effect on TNBC cells has never been explored.
Methods: The dose-response effects and time course of effects of SeC on three different TNBC cell lines, MDA-MB-231, MDA-MB-436 and MDA-MB-468, were investigated in this study. Cellular viability was determined by the CCK-8 assay and cell morphology were recorded under a light microscope. Cellular apoptosis was detected using Annexin V/PI staining assay and cell cycle distribution was analyzed by flow cytometry.
Results: SeC induced cell growth inhibition in all three TNBC cell lines. For 24, 48 and 72 hours of SeC treatments, the IC50 values were 40.8, 12.8 and 9.2 μM for MDA-MB-231 cells; 14.6, 5.4 and 3.0 μM for MDA-MB-436 cells; and 69.6, 29.3 and 19.9 μM for MDA-MB-468 cells. The changes of cellular morphology of TNBC cells in response to SeC treatment were similar to those cells undergoing apoptotic pathway. This result was confirmed by Annexin V/PI staining assays (Table 1). Cell cycle analysis further revealed that SeC also induced S-phase arrest in a dose-dependent manner (Table 2).
Conclusion: In summary, SeC inhibited TNBC cell viability in a dose- and time-dependent manner which was attributed to the induction of apoptosis and S-phase arrest. Our finding indicates that SeC is a potential therapeutic agent for TNBC.
Table 1. Apoptotic rate of TNBC cells after SeC treatment.Conc.(μM)MDA-MB-231MDA-MB-436MDA-MB-46805.8 %18.1 %26.7 %1025.5 %45.8 %60.7 %2040.1 %67.1 %70.9 %4054.7 %70.7 %74.5 %
Table 2. SeC induces S-phase arrest in TNBC cells in a dose-dependent manner. Conc.(μM)G0/G1 (%)S (%)G2/M (%)MDA-MB-231016.655.927.5 1050.139.310.6 2045.548.16.4 4041.753.05.3MDA-MB-436042.127.630.3 1036.335.028.7 2034.340.725.0 4032.445.422.2MDA-MB-468059.123.717.2 1054.929.315.8 2050.135.714.2 4043.843.113.1
Citation Format: Long M, Qiu W, Wu J, Liu R, Su H. Selenocystine inhibits triple-negative breast cancer cell proliferation by inducing cell apoptosis and S-phase arrest. [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 P5-03-12.
Abstract P5-04-06: Analysis of STEAP1 expression as a therapeutic target in breast cancer
Authors: Aft R , Mudalagiriyappa C , Pillai S , Watson M 
Published: May 2016

Abstract
Objective: The six transmembrane epithelial antigen of the prostate (STEAP1) is predominantly overexpressed in human prostate cancer. STEAP1 was first identified as a prostate-specific cell-surface antigen and found to be up-regulated in various cancers including lung, bladder, colon, and ovarian with little expression in normal tissue. An anti-STEAP1 monoclonal antibody linked to an antimitotic agent is currently in Phase I clinical trials for prostate cancer patients. Microarray data from our lab suggested that STEAP1 is also highly expressed in human breast cancers and bone marrow disseminated tumor cells. In this study we evaluate expression STEAP1 in primary tumors, and bone marrow (BM) from breast cancer patients.
Experimental procedures: RNA was isolated from primary tumor, non-malignant breast tissue and bone marrow (BM) from stage II and III breast cancer patients, healthy volunteers, breast cancer cell lines and BM from patient derived xenographs (PDX). Disseminated tumor cells (DTCs) from patient BM were enriched by microfiltration and analyzed by RNA-in situ hybridization (ISH). STEAP1 RNA expression was analyzed by Nanostring nCounter and qRT-PCR using human specific probes. STEAP1 immunohistochemical (IHC) staining of human tissue was performed using standard protocols. Knockdown of steap1 expression was accomplished using a lentiviral system.
Results: STEAP1 mRNA was up-regulated in 77% of tumors (28/36) compared to the corresponding normal tissue. STEAP1 protein was expressed in 100% of tumors (8/8) and was absent in non-malignant breast tissue (7/7) by IHC staining. STEAP1 mRNA was not expressed normal BM, but was detected in 8% (6/74) of BM from patients with early stage breast cancer. STEAP1 expression in the BM was associated with triple negative disease (3/6) and recurrent disease development (4/6, p=.028). STEAP1 expression was observed in individual DTCs isolated from patients BM, while no expression was observed in normal BM. In a PDX model of breast cancer, STEAP1 expression in BM was only observed in mouse who developed metastatic disease associated (7/10, p=.004). Knockdown of STEAP1 in the breast cancer cell line MDA-MB231 cells inhibited cell growth by 80-90%.
Conclusion: STEAP1 is expressed in human breast tumors and disseminated tumor cells found in the bone marrow of breast cancer patients. Expression of STEAP1 in the BM is significantly associated with the development of metastatic disease in patients as well as in a mouse model of breast cancer. Our data indicate that STEAP1 could serve as a therapeutic target for the treatment of minimal residual disease in breast cancer.
Citation Format: Aft R, Mudalagiriyappa C, Pillai S, Watson M. Analysis of STEAP1 expression as a therapeutic target 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 P5-04-06.
Abstract P5-04-14: The covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death in basal-like breast cancer cell lines
Authors: Ebelt ND , Van Den Berg CL 
Published: May 2016

Abstract
Basal-like and claudin-low breast cancers have the worst prognosis and represent 15-20% of breast cancers diagnosed each year. Endocrine and molecularly targeted therapies, such as trastuzumab, are ineffective due to lack of ER expression or HER2 amplification in the tumors. They also have a high frequency of p53 mutations, low BRCA1 expression and high EGFR expression. Our lab has shown that high expression of JNK2 in human basal-like breast cancers leads to significantly decreased disease-free survival. JNK2 also promotes basal-like tumor progression in mice by increasing EGFR-mediated migration through facilitating internalization of EGFR, upregulating EMT gene expression and promoting metastasis.
The ATP-competitive JNK inhibitor SP600125 has been commonly used by researchers to elucidate JNK-specific mechanisms, but this inhibitor was found to have high affinity to many other intracellular kinases. A new JNK inhibitor, JNK-IN-8, has been developed that binds covalently to all three JNK gene products and is more selective than the SP600125 compound (Zhang, et al. 2012). Using this inhibitor, we have found that basal-like breast cancer cell lines can become sensitized to lapatinib. This combination is synergistic and causes apoptotic cell death, while as single agents at these concentrations, these drugs have little effect on cell viability. Treatment with either lapatinib or JNK-IN-8 decreases transcriptional activity of NF-κB significantly, but combination of the two drugs reduces NF-κB activity to an almost negligible amount compared to vehicle treatment. Combination treatment also led to a 6-fold increase in ROS production that may be activating apoptosis.
We hypothesize that inhibition by both JNK-IN-8 and lapatinib cause independent decreases in NF-κB activation that, when combined, cause a synergistic decrease in NF-κB-mediated survival mechanisms. Use of the JNK-IN-8 inhibitor with lapatinib in humans may increase survival in patients with basal-like or claudin-low breast cancers.
Zhang, T. et al. "Discovery of potent and selective covalent inhibitors of JNK". Chem Biol. 2012 Jan 27;19(1):140-54.
Citation Format: Ebelt ND, Van Den Berg CL. The covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death in basal-like breast cancer cell lines. [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 P5-04-14.
Abstract P5-04-20: TLE1 protein expression in HER2-positive and triple-negative breast cancer
Authors: Lee HJ , Oh M-H , Lee J-H , Cho HD , Jang S-H , Jung HY , Kim K-J 
Published: May 2016

Abstract
Purpose
Transducin-like enhancer protein 1 (TLE1) is a member of the Groucho (Gro)/TLE family of transcriptional co-repressors that regulate the transcriptional activity of a wide range of genes. TLE1 has been shown to be a specific and diagnostically useful immunohistochemical marker for synovial sarcoma. However, there have been few reports of the status of TLE1 in breast cancers. The purpose of this study was to clarify the nuclear expression of TLE1 in 511 Korean breast cancers by immunohistochemistry (IHC) and to correlate the findings to clinicopathologic variables including prognostic significance.
Methods
IHC was performed on tissue microarrays (TMAs) in 511 cases of breast cancer. Associations between the TLE1 expression and the clinicopathologic characteristics were retrospectively analyzed. Progression-free survival and disease-specific survival was assessed by the Kaplan–Meier method and Cox regression model.
Results
Of 511 cases of breast cancer, high expression of the TLE1 was detected in 63 (12.3%) cases. TLE1-high expression was strongly associated with HER2-positive breast cancer phenotype (p &lt; 0.001) and triple-negative breast cancer phenotype (p &lt; 0.001). Furthermore, high TLE1was significantly associated with high histologic grade (p &lt; 0.001), node-negative (p =0.011), estrogen receptor negativity (p &lt; 0.001), progesterone receptor negativity (p &lt; 0.001), CK5/6 positivity (p &lt; 0.001), epidermal growth factor receptor positivity (p &lt; 0.001), high ki-67 proliferative index (p &lt; 0.001) and high p53 expression (p &lt; 0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease progression and cancer-related death (p =0.112 and p =0.068, respectively).
Conclusion
Our results show that high TLE1expression is significantly associated with HER2-positive and triple-negative breast cancer. TLE1 may represent a potential therapeutic target for this aggressive disease, which warrants further investigation.
Citation Format: Lee HJ, Oh M-H, Lee J-H, Cho HD, Jang S-H, Jung HY, Kim K-J. TLE1 protein expression in HER2-positive and 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 P5-04-20.
Abstract P5-06-05: MED12 exon 2 mutations in phyllodes tumors of the breast
Authors: Nagasawa S , Ohta T , Tsugawa K 
Published: May 2016

Abstract
Exon 2 of MED12, a subunit of the transcriptional mediator complex, has been frequently mutated in uterine leiomyomas and breast fibroadenomas; however, it has been rarely mutated in other tumors. Although the mutations were also found in uterine leiomyosarcomas, the frequency was significantly lower than in uterine leiomyomas.
Here, we examined the MED12 mutation in phyllodes tumors, another biphasic tumor with epithelial and stromal components related to breast fibroadenomas. Mutations in
MED12 exon 2 were analyzed in nine fibroadenomas and eleven phyllodes tumors via
Sanger sequencing. A panel of cancer- and sarcoma-related genes was also analyzed using Ion Torrent next-generation sequencing. Six mutations in fibroadenomas, including those previously reported (6/9, 67%), and five mutations in phyllodes tumors (5/11, 45%) were observed. Three mutations in the phyllodes tumors were missense mutations at
Gly44, which is common in uterine leiomyomas and breast fibroadenomas. In addition, two deletion mutations (in-frame c.133_144del12 and loss of splice acceptor
c.100-68_137del106) were observed in the phyllodes tumors. No other recurrent mutation was observed with next-generation sequencing. Frequent mutations in MED12 exon 2 in the phyllodes tumors suggest that it may share genetic etiology with uterine leiomyoma, a subgroup of uterine leiomyosarcomas and breast fibroadenoma.
Citation Format: Nagasawa S, Ohta T, Tsugawa K. MED12 exon 2 mutations in 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 P5-06-05.
Abstract P5-07-06: A competing risks analysis of the association between prediagnostic serum glucose and lipids and breast cancer survival
Authors: Wulaningsih W , Vahdaninia M , Rowley M , Holmberg L , Garmo H , Malmstrom H , Lambe M , Hammar N , Walldius G , Jungner I , Coolen A , Van Hemelrijck M 
Published: May 2016

Abstract
Background: Abnormal levels of glucose and lipids may be linked to survival after breast cancer (BC) diagnosis, but their association to other causes of mortality such as cardiovascular (CV) disease may result in a competing risk problem and invalidate conventional analyses.
Methods: We assessed serum glucose, triglycerides (TG) and total cholesterol (TC) measured prospectively three months to three years before diagnosis in 1,798 women with BC in the Swedish Apolipoprotein Mortality Risk Study (AMORIS). In addition to using multivariable Cox proportional hazards regression, we employed latent class proportional hazards models to capture any heterogeneity of associations between these markers and BC death. The latter method was extended to include the primary outcome (BC death) and competing outcomes (CV death and death from other causes), allowing latent class-specific hazard estimation for cause-specific deaths.
Results: No association between prediagnostic glucose, TG or TC with BC death was observed with Cox regression. With latent class proportional hazards model, two latent classes (Class I and II) were identified in the cohort. Class I, comprising the majority (81.5%) of BC patients, had an increased risk of BC death following higher TG levels (HR: 1.87, 95% CI: 1.01-3.45 for every log TG increase). Lower overall survival was observed in Class II, but no association for BC death was found. On the other hand, TC positively corresponded to CV death in Class II, and similarly, glucose to death from other causes.
Conclusion: Higher TG was associated with an increased risk of BC death in the majority of BC patients. Our study also identified a subgroup of BC patients at higher risk of early death likely driven by other metabolic-related diseases, which adds to our understanding into BC survival in presence of competing outcomes.
Citation Format: Wulaningsih W, Vahdaninia M, Rowley M, Holmberg L, Garmo H, Malmstrom H, Lambe M, Hammar N, Walldius G, Jungner I, Coolen A, Van Hemelrijck M. A competing risks analysis of the association between prediagnostic serum glucose and lipids and breast cancer survival. [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 P5-07-06.