bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-12-04: De-escalating doses of letrozole in post menopausal women at high risk for breast cancer
Authors: Lopez Ana Maria , Chow Hsiao Hui Sherry , Frank Denise , Puthi Sandhya , Boughey Judy , Hsu Paul , Guillen Jose , Perloff Marjorie , Ley Michelle , Lang Julie E 
Published: May 2015

Abstract
Background: Although breast cancer (BC) may occur at any age, its prevalence is greater postmenopause. Greater than 75 % of postmenopausal BCs are hormone dependent. Aromatase inhibitors suppress postmenopausal estrogen biosynthesis. Letrozole has demonstrated efficacy against BC in the adjuvant and metastatic setting at the treatment dose of 2.5 mg daily. Its potential role in BC prevention has been inferred from reductions in contralateral BCs. Its side effect profile, similar to other AIs, includes exacerbation of menopausal symptoms that negatively impact quality of life (QOL) and may result in discontinuation of the drug. Both anastrazole and exemestane have been demonstrated to reduce BC in high-risk women.
Hypothesis: Lower and intermittent doses of letrozole effectively suppress estrogen in the high-risk postmenopausal woman and provide a better side effect profile.
Methods: A randomized, double-blind study comparing the impact of varying letrozole doses (2.5 mg daily, 2.5 mg MWF, 1.0 mg MWF, or 0.25 mg MWF) on estrogen suppression and side effects--lipids, bone resorption, menopause, and QOL-- was conducted. Participants randomized to intermittent dosing received placebo on nontreatment days.
Results: 112 participants were enrolled at 2 clinical sites. Mean patient age was 62.8 years, and average BMI was 29.8. Analysis of available data after 24 weeks of therapy revealed statistically significant increase in triglycerides (N=94): 114.67±48.39 to 125.79±54.31 (p&lt;0.01); vasomotor symptoms (N=95): 2.25±1.26 to 2.74±1.67 (p&lt;0.01); and C-telopeptide (N=75): 0.39±0.23 to 0.55±0.28 (p&lt;0.0001). Statistically significant decrease in estradiol (N=68): 5.57±5.19 to 1.26±1.41 (p&lt;0.0001) and estrone (N=68): 22.39±13.02 to 1.64±2.66 (p&lt;0.0001) were observed. No differences in QOL (SF 36) were noted after letrozole treatment. P-values were derived from paired t-test (signed rank test) for the difference between baseline and after 24 weeks of study drug.
Conclusions: De-escalating doses of letrozole suppress postmenopausal estrogen effectively and result in statistically significant increases in triglycerides, C-telopeptide and vasomotor symptoms without impact on QOL. Presentation will include unblinded intervention arm outcomes.
Citation Format: Ana Maria Lopez, Hsiao Hui Sherry Chow, Denise Frank, Sandhya Puthi, Judy Boughey, Paul Hsu, Jose Guillen, Marjorie Perloff, Michelle Ley, Julie E Lang. De-escalating doses of letrozole in post menopausal women at high risk for breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-12-04.
Abstract P5-15-22: Evaluation of quality of life in patients with advanced and metastatic breast cancer proposed for palliative chemotherapy and best supportive care versus best supportive care
Authors: Ciuhu Anda-Natalia T , Rahnea Nita Gabriela I , Popescu Mihaela T , Rahnea Nita Roxana Andreea D 
Published: May 2015

Abstract
Background:
In Romania many patients neglect their symptoms and present to the doctor in advanced stages of cancer. In the case of patients with breast cancer who present with very advanced locoregional disease (ulcerated or hemorrhagic tumors) and symptomatic metastatic disease (visceral or skeletal pain, dyspnea), the choice between chemotherapy/hormonal therapy and best supportive care and only best supportive care became very difficult.
Objective:
Evaluation of quality of life in patients with advanced and metastatic breast cancer proposed for palliative chemotherapy and best supportive care versus best supportive care
Materials and methods:
In the last 6 month of the year 2013, 57 patients with advanced and metastatic breast cancer were randomized to either chemotherapy/hormonal therapy in addiction to best supportive care or to best supportive care. The patients were naive to chemotherapy, with performance status – ECOG between 2 and 3 and had symptomatic disease. The randomization of patients was made according to their choice. The performance status and the symptoms were evaluated at the baseline and, later, at each admission in the Oncology Palliative Care Department.
Results:
More patients in the chemotherapy group (92.68%, 38/41) had an improve quality of life compared to those in the best supportive care group (56.25 %, 9/16). The overall survival was longer in the chemotherapy group.
Conclusions:
The results show that chemotherapy/hormonal therapy improve the quality of life and overall survival in very advanced locoregional disease and symptomatic metastatic breast cancer. The number of patients who benefit from chemotherapy and best supportive care is higher versus patients who benefit only from best supportive care.
Key words: chemotherapy/hormonal therapy, best supportive care, breast cancer.
Citation Format: Anda-Natalia T Ciuhu, Gabriela I Rahnea Nita, Mihaela T Popescu, Roxana Andreea D Rahnea Nita. Evaluation of quality of life in patients with advanced and metastatic breast cancer proposed for palliative chemotherapy and best supportive care versus best supportive care [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-22.
Abstract P5-16-01: End-of-life outcomes and hospice and palliative care utilization in hospitalized patients with metastatic breast cancer
Authors: Parkes Amanda , Shin Jennifer A , Knight Helen , El-Jawahri Areej , Traeger Lara , Temel Jennifer S 
Published: May 2015

Abstract
Background:
Hospitalizations in patients with metastatic cancer occur commonly at the end of life but have not been well-described in those with metastatic breast cancer (MBC). The goal of this study was to describe the reasons for admission, end-of-life outcomes, and hospice and palliative care utilization in hospitalized patients with MBC.
Methods:
We identified all patients with MBC who had their first hospital admission (index admission) at Massachusetts General Hospital since their diagnosis of metastatic disease between 1/1/2009 and 12/31/2010 through a centralized clinical data registry. We collected demographic and clinical information and data on all hospital admissions and utilization of palliative care and hospice services during a three-year follow-up period.
Results:
We identified 123 patients hospitalized for the first time since their diagnosis of MBC. The median number of hospital admissions during the three-year follow-up period was 2 (range 1 to 17). Uncontrolled symptoms accounted for half (62/123, 50%) of the index admissions [20 (16%) with central nervous system systems, 17 (14%) with respiratory symptoms, 10 (8%) with pain, 9 (7%) with gastrointestinal symptoms, 4 (3%) with failure to thrive, and 2 (2%) with dehydration]. The majority of patients (93/123, 76%) died during the follow-up period. The median time from first hospitalization to death was 6 months (range 0 to 53). Among patients who died, 20/93 (22%) died in the hospital and 49/93 (53%) died within 14 days of hospital discharge. Among the deceased group, the inpatient palliative care team evaluated 53/93 (57%) of patients at least once during an admission, but only 18/93 (19%) patients attended an outpatient palliative care clinic appointment. A minority of patients who died (27/93, 29%) were referred to hospice upon discharge. An additional 34/93 (37%) patients who died were referred to hospice from the outpatient setting.
Conclusions:
Hospitalized patients with MBC are commonly admitted for uncontrolled symptoms. They have a poor prognosis, and approximately half die within two weeks of a hospital admission. However, only a minority receive outpatient palliative care or are referred to hospice services from the inpatient setting. These findings highlight the need to develop interventions to improve end-of-life care for patients with MBC who are hospitalized.
Citation Format: Amanda Parkes, Jennifer A Shin, Helen Knight, Areej El-Jawahri, Lara Traeger, Jennifer S Temel. End-of-life outcomes and hospice and palliative care utilization in hospitalized patients with metastatic breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-16-01.
Abstract P6-01-17: AQP3 expression predicts survival in patients with HER2-positive early breast cancer
Authors: Chae Yee Soo , Lee Soo Jung , Lee Jeeyeon , Jung Jin Hyang , Park Ho Yong 
Published: May 2015

Abstract
Background: Recent studies have revealed aquaporins (AQPs) as targets for novel anti-tumor therapy, since they likely play a role in carcinogenesis, tumor progression, and invasion. Accordingly, we analyzed the prognostic impact of AQP3 expression and polymorphisms in a number of patients with early breast cancer (EBC).
Patients and Methods: AQP3 expression was investigated on the basis of the immunohistochemistry of tissue microarray specimens from 447 EBC patients who underwent surgery between 2003 and 2008. We scored the staining intensity (0 through3) and percentage of positive tumor cells (0 through 4), and the staining score was defined as sum of these scores used to categorize the AQP3 expression as negative (0 through 2), weak (3 through 5), or strong (6 or more). For AQP3 polymorphisms, seven SNPs (rs10813981, rs34391490, rs591810, rs2227285, rs2228332, rs17553719, and rs3860987) were selected using in silico analysis and genotyped using the Sequenom MassARRAY.
Results: A total of 180 (40.3%) of the patients were identified as AQP5-positive (staining score &gt;2), including 86 (19.2%) cases of strong expression (stating score &gt;5). In a univariate analysis, AQP3 expression was significantly associated with survival for the patients with HER2-overexpressing EBC. Moreover, a multivariate survival analysis revealed that AQP3 expression was an independent prognostic marker of disease-free survival (DFS: HR=3.137, 95%CI=1.079-9.125, p=0.036; Distant DFS: HR=2.784, 95%CI=0.921-8.414, p=0.070) for the HER2-overexpressing EBC patients. Meanwhile, none of selected AQP3 polymorphisms were related with AQP3 expression in tumor tissue nor survival in the current study.
Conclusion: AQP3 expression in tumor tissue may be considered as a potential prognostic marker in patients with HER2-overexpressing EBC after curative surgery.
Citation Format: Yee Soo Chae, Soo Jung Lee, Jeeyeon Lee, Jin Hyang Jung, Ho Yong Park. AQP3 expression predicts survival in patients with HER2-positive early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-17.
Abstract P6-03-04: TGF-β receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer
Authors: Jovanovic Bojana , Beeler J Scott , Pickup Michael W , Chytil Anna , Gorska Agnieszka E , Ashby William J , Lehmann Brian D , Zijlstra Andries , Pietenpol Jennifer A , Moses Harold L 
Published: May 2015

Abstract
Introduction: There is a major need to better understand the molecular basis of triple negative breast cancer (TNBC) in order to develop effective therapeutic strategies. Using gene expression data from 587 TNBC patients we previously identified six subtypes of the disease, among which a Mesenchymal-Stem Like (MSL) subtype. The MSL subtype has significantly higher expression of the transforming growth factor beta (TGF-β) pathway-associated genes relative to other subtypes, including the TGF-β receptor type III (TβRIII). We hypothesize that TβRIII is tumor promoter in mesenchymal-stem like TNBC cells.
Methods: Representative MSL cell lines SUM159, MDA-MB-231 and MDA-MB-157 were used to study the roles of TβRIII in the MSL subtype. We stably expressed short hairpin RNAs specific to TβRIII (TβRIII-KD). These cells were then used for xenograft tumor studies in vivo; and migration, invasion, proliferation and three dimensional culture studies in vitro. Furthermore, we utilized human gene expression datasets to examine TβRIII expression patterns across all TNBC subtypes.
Results: TβRIII was the most differentially expressed TGF-β signaling gene in the MSL subtype. Silencing TβRIII expression in MSL cell lines significantly decreased cell motility and invasion. In addition, when TβRIII-KD cells were grown in a three dimensional (3D) culture system or nude mice, there was a loss of invasive protrusions and a significant decrease in xenograft tumor growth, respectively. In pursuit of the mechanistic underpinnings for the observed TβRIII-dependent phenotypes, we discovered that integrin-α2 was expressed at higher level in MSL cells after TβRIII-KD. Stable knockdown of integrin-α2 in TβRIII-KD MSL cells rescued the ability of the MSL cells to migrate and invade at the same level as MSL control cells.
Conclusions: We have found that TβRIII is required for migration and invasion in vitro and xenograft growth in vivo. We also show that TβRIII-KD elevates expression of integrin-α2, which is required for the reduced migration and invasion, as determined by siRNA knockdown studies of both TβRIII and integrin-α2. Overall, our results indicate a potential mechanism in which TβRIII modulates integrin-α2 expression to effect MSL cell migration, invasion, and tumorigenicity.
Citation Format: Bojana Jovanovic, J Scott Beeler, Michael W Pickup, Anna Chytil, Agnieszka E Gorska, William J Ashby, Brian D Lehmann, Andries Zijlstra, Jennifer A Pietenpol, Harold L Moses. TGF-β receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-03-04.
Abstract P6-06-01: Studies on tumor heterogeneity using a preclinical model of breast cancer caused by genetic alteration of the ATX-LPA axis
Authors: Federico Lorenzo , Jeong Kang Jin , Zhang Dong , Ju Zhenlin , Chong Zechen , Dennison Jennifer B , Mills Gordon B 
Published: May 2015

Abstract
Targeted alterations of the ATX/LPA signaling axis in mice creates a tumorigenic environment from which mammary neoplasias can develop. Using mammary tumors derived from this model, we have established a transplantation procedure in which fragments of different tumors are orthotopically transplanted in syngeneic mice. Under these conditions, primary murine tumors displayed a wide spectrum of growth rates suggesting that alteration of ATX/LPA signaling axis engenders a variety of different breast cancer subtypes with distinctive propensity to progress, which is similarly observed in human neoplastic disease. Comprehensive analysis of high-throughput RNAseq and Reverse Phase Protein Array (RPPA) data revealed that despite being passaged multiple times, tumors retained their distinct growth profiles and also maintained surprisingly stable molecular characteristics. The remarkable consistency in terms of growth, transcriptional landscape, and protein expression demonstrates that in this model a small fragment randomly taken from any region of the tumor can accurately and reproducibly regenerate an entire developmental program when grown in vivo. It follows that each consistent molecular change detected in the tumor likely represents either a marker of the tumor or its mechanistic oncodriver. Using unbiased multidimensional scaling analysis of RNAseq data we have identified tumors that were strictly related to normal mammary tissue in terms of gene expression as well as individual gene signatures that differentiate slow- vs fast-growing tumors. Furthermore, we have identified several stable alterations at a protein level that are commonly found in human breast cancers including cMYC, BRCA2, PARP1, Claudin-7, Her3, and E-Cadherin. These results demonstrate that an orthotopic transplantation procedure in immunocompetent hosts represents a relevant preclinical platform to probe human breast cancer heterogeneity and pinpoint molecular alterations that are mechanistically responsible for malignant behavior.
Citation Format: Lorenzo Federico, Kang Jin Jeong, Dong Zhang, Zhenlin Ju, Zechen Chong, Jennifer B Dennison, Gordon B Mills. Studies on tumor heterogeneity using a preclinical model of breast cancer caused by genetic alteration of the ATX-LPA axis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-06-01.
Abstract P6-06-02: Molecular characterization of a patient-derived xenograft (PDX) resource for triple negative breast cancer
Authors: Graber Joel H , Keck James G , Airhart Susan D , Bult Carol J , Liu Edison T 
Published: May 2015

Abstract
The Jackson Laboratory (JAX) has developed a resource of human tumors implanted into immune deficient mice (patient derived xenografts; PDX) as a platform for testing standard of care and novel therapeutic options for Triple Negative Breast Cancer. PDX models provide an advantage over cell culture based models for testing therapeutic interventions because they retain properties such as tumor cell heterogeneity that are critical to the biological properties of a patient’s tumor and response to treatment.
Tumor material acquired from biopsy or surgical resection was implanted subcutaneously into the flank of immune deficient NOD-scid IL2r gamma-chain null (NSG) mice. The PDX resource currently contains 21 established breast cancer PDX models (12 TNBC) with 24 additional models currently in development. Two of the established TNBC PDX models have BRCA1 mutations. The median age of the patients from whom tumor material was obtained for all breast models is 53 (45-89).
Tumors that successfully engrafted were characterized for somatic mutations using the new JAX Clinical Cancer Panel, Copy Number Variants using the Affymetrix human 6.0 SNP array, and gene expression using both Affymetrix U133 plus v2 and RNA-Seq. Normalized gene expression was analyzed for characteristic patterns in a pan-cancer approach across all PDX models and further compared with the previously identified TNBC molecular subtypes (Lehmann et al. 2011. JCI 121:2750-2767). The combination of principal components analysis and classification via expression pattern resulted in putative matches of models to most of the known molecularly defined subtypes of TNBC tumors.
Tumor bearing mice for the TNBC PDX models have been treated with docetaxel, cisplatin, cyclophosphamide and doxorubicin. Preliminary studies of tumor response to these treatment regimes revealed systematic differences that can be correlated with features of the genomic analysis, including expression subtype characterization.
The JAX collection of TNBC cancer PDX models is a well-annotated, publically available resource of models with deep genomic characterization and standard of care therapy response data for use in the development of advanced therapeutic options. Genomically defined subgroups within the collection suggest strategies to refine patient selection and treatment algorithms. Information about the models along with summarized genomic data is publicly available at the Mouse Tumor Biology database PDX web portal (http://tumor.informatics.jax.org).
Citation Format: Joel H Graber, James G Keck, Susan D Airhart, Carol J Bult, Edison T Liu. Molecular characterization of a patient-derived xenograft (PDX) resource for triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-06-02.
Abstract P6-06-04: The role of sphingosine kinase 1 in breast carcinogenesis
Authors: Shimizu Yoshiko , Furuya Hideki , Tamashiro Paulette M , Iino Kayoko , Rosser Charles J , Kawamori Toshihiko 
Published: May 2015

Abstract
Introduction: The bioactive sphingolipids, ceramide/sphingosine and sphingosine 1-phosphate (S1P) possess opposite effects on cell fate. Sphingosine kinase 1 (SphK1) is an enzyme that principally regulates the balance or the "rheostat" of the sphingolipids by phosphorylating sphingosine to form S1P. In this study, we investigated the effect of SphK1 deficiency on HER2/neu-induced mammary carcinogenesis using a MMTV-neu transgenic (Tg) mice model. Methods: MMTV-neu Tg mice were crossbred with SphK1 knockout (KO) mice to generate MMTV-neu Tg mice with KO or wild-type for SphK1 gene. The number and size of the palpable tumors were recorded weekly until mice reached 35 weeks of age or the largest tumor diameter reached 20 mm in size. At necropsy, tumors and blood were collected for analysis. The sphingolipid profiles in blood were analyzed using tandem mass spectrometry. Results: The incidences of mammary tumor development in the homozygous SphK1 KO (1/13; 8%) and heterozygous SphK1 KO (11/44; 26%) were significantly reduced (P=0.0112 and 0.0208, respectively) when compared to wild-type mice (8/13; 62%). The mammary tumor multiplicity was significantly reduced in homozygous SphK1 KO (0.08±0.08; P=0.0036) when compared to wild-type mice (0.69±0.17). The S1P levels in blood were significantly decreased in homozygous SphK1 KO mice (P&lt;0.0001), while sphingosine levels were significantly increased in the blood of heterozygous SphK1 KO mice (P&lt;0.001). In both homozygous and heterozygous SphK1 KO mice, the blood level of C16:0-Ceramide was significantly increased (P&lt;0.001). Conclusion: The results provide novel evidence that SphK1 mediates HER2/neu-induced mammary carcinogenesis by regulating the ceramide/sphingosine-S1P "rheostat". Thus, we propose that SphK1 inhibition may be a novel therapeutic option in the treatment of HER2 breast tumors.
Citation Format: Yoshiko Shimizu, Hideki Furuya, Paulette M Tamashiro, Kayoko Iino, Charles J Rosser, Toshihiko Kawamori. The role of sphingosine kinase 1 in breast carcinogenesis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-06-04.