bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-07-05: LOC283299 suppress the lymphnode metastatic cascade in breast cancer patients
Authors: Guo R , Xue J , Su Y , Xiu B , Ji W , Chi Y , Wu J 
Published: February 2018

Abstract
Background
Long non-coding RNAs (lncRNAs) have been proved to play an essential role in cancer metastasis. The accuracy of intraoperative assessment of lymph nodes metastasis need to be improved. In this study, we aimed to define the lncRNA biomarker ectopic expressed in breast cancer patients' metastatic lymph nodes, and to explore the potential molecular mechanisms.
Experimental Design
RNA-seq analyses in 3 paired breast cancer patients' primary tumor and metastatic lymph node was used as training set to determine differentially expressed lncRNAs that may be associated with lymph node metastasis. The other 40 patients were analyzed as validation set to test the accuracy of lncRNAs identification by quantitative real-time PCR. The correlation between LOC283299 expression level and prognosis in other 282 breast cancer patients was confirmed. In parallel, in vitro and in vivo analyses were carried out to determine the potential mechanisms of LncRNA-dependent lymph node metastases and prognosis.
Results
RNA-seq analyses in the training set revealed significant correlation between high expression level of LOC283299 and lower lymph node metastasis potential in breast cancer patients. We further validated that the expression level of LOC283299 was significantly higher in tumor primary tissue than that in paired metastatic lymph node (P=0.0245), and higher LOC283299 expression level was markedly associated with good metastasis-free survival in breast cancer patients (P=0.04). In breast cancer cell lines, CRISPR-on overexpression of LOC283299 inhibited proliferation, migration, invasion, and metastases both in vivo and in vitro. shRNA knockdown LOC283299 promotes the ability of tumor proliferation and metastasis. The molecular mechanisms by which LOC283299 as metastasis-suppressing lncRNAs regulates recurrence and metastasis may involve regulation of epithelial to mesenchymal transition (EMT), cellular invasion and microenvironment in breast cancer cells.
Conclusion
Our study revealed a strong correlation between LOC283299 expression and lymph node metastases in breast cancers. High level of LOC283299 was associated with better metastasis-free survival. The changed metastasis phenotype may be mediated by the interaction of LOC283299 and breast cancer cells. Therefore, LOC283299 may represent a potential predictive biomarker for early lymph node metastasis in breast cancer.
Citation Format: Guo R, Xue J, Su Y, Xiu B, Ji W, Chi Y, Wu J. LOC283299 suppress the lymphnode metastatic cascade in breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-05.
Abstract P5-07-11: BHLHE40-AS1 is an enhancer associated noncoding RNA critical to breast cancer progression
Authors: DeVaux RKS , Schimjawicz H , Coarfa C , Behbod F , Herschkowitz JI 
Published: February 2018

Abstract
Increased emphasis on breast cancer screening has led to a dramatic increase in diagnosis of ductal carcinoma in situ (DCIS). DCIS lesions are nonobligate precursors of invasive ductal carcinoma (IDC) and thus, the current standard-of-care is aggressive therapy to prevent invasive and metastatic disease. However, only ˜40% of DCIS cases are predicted to progress leading to a current state of overtreatment and overdiagnosis. Thus, there is a critical need to identify functional determinants of progression of DCIS to IDC to allow discrimination between indolent and aggressive breast cancers and refine patient treatment strategies. We propose that long noncoding RNAs (lncRNAs) functionally drive breast cancer progression and their expression can discriminate between innocuous and potentially invasive DCIS.
Using biopsies from women with tandem DCIS and IDC lesions, we identified the lncRNA BHLHE40-AS1 as enriched in patient IDC. Furthermore, BHLHE40-AS1 is enriched in multiple breast cancer progression models, in HER2+ cell lines, and can be induced by expression of HER2. BHLHE40-AS1 is transcribed from a known super-enhancer that we find becomes rewired in breast cancer progression. In addition, the lncRNA is found antisense to BHLHE40, a transcription factor critical to many core processes (apoptosis, EMT, circadian rhythm). Depletion of the lncRNA attenuates expression of BHLHE40. Future studies are focused on mechanistically elaborating its function, its impact on the associated enhancer and chromatin looping, and determining the utility of BHLHE40-AS1 as a clinically relevant biomarker and therapeutic target in invasive breast cancer.
Citation Format: DeVaux RKS, Schimjawicz H, Coarfa C, Behbod F, Herschkowitz JI. BHLHE40-AS1 is an enhancer associated noncoding RNA critical to breast cancer progression [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-11.
Abstract P5-12-03: Withdrawn
Authors: Wood M , Seisler DK , Hsieh M-K , Kontos D , Ambaye A , Le-Petross H , Jung S-H , Liu H , Zekan P , Cardinal L , Charlamb J , Wang LX , Unzeitig GW , Garber J , Marshall J 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P5-15-02: Withdrawn
Authors: Crew KD , Anderson G , Hershman DL , Terry MB , Tehranifar P , Lew DL , Yee M , Brown EA , Kairouz SS , Minasian LM , Ford L , Neuhouser ML , Arun BK , Brown PH 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract P6-07-02: Bisphenol A treatment induces hyperplasia in primary and stem cell-generated mammary glands from pregnant mice
Authors: Bouamar H , Zhang F , Gu X , Dong Q , Sun L 
Published: February 2018

Abstract
Breast cancer is a commonly diagnosed cancer of pregnancy. However, how endogenous and exogenous endocrine factors may contribute to the development of pregnancy-associated mammary tumorigenesis is not clear. There is growing evidence that mammary stem cells (MaSCs) may initiate neoplastic transformation when dysregulated in mouse models. We investigated the effect of the environmental endocrine disruptor bisphenol A (BPA) on mouse mammary gland morphology, epithelial cell composition, pre-neoplastic lesions, and the regenerative function of MaSCs. Pregnant FVB mice with GFP transgene on Day E8.5 were implanted with osmotic pumps that constantly release BPA at 0, 25 or 250 ng/kg/day for 28 days and the mice were euthanized one month after weaning. In agreement with the literature, we observed an abnormality of the morphology of the mammary gland after BPA treatment characterized by higher duct density and abnormal secondary and tertiary branching. Quantification of percent hyperplastic mammary ducts in H&E-stained tissue slides revealed a significant increase of ducts with hyperplastic lesions after BPA treatment, particularly with the low dose. To investigate the effects of BPA treatment on MaSCs, we used enzyme digestion to isolate the CD24hi/CD49f+ luminal epithelial cells (also termed as colony forming cell or CFC) and the CD24+/CD49fhi basal epithelial cells (also termed as mammary repopulating unit or MRU) from mammary gland tissues by FACS and found no significant difference in percent of luminal or basal cell population after BPA treatment. Because the basal cells are enriched with MaSCs that can form mammospheres in suspension culture and subsequently form solid 3D organoids when cultured in Matrigel, we transplanted the solid 3D organoids into cleared mammary fat pads of syngeneic FVB mice and immune-compromised nude mice to examine how BPA treatment might alter MaSC function. Significantly, similar to the results from the primary mammary glands, the regenerated mammary glands by MaSCs from mice treated with the low dose of BPA showed increased duct density, secondary and tertiary branching, and a significantly greater number of hyperplastic lesions. Taken together, our study demonstrated that BPA exposure at very low dose could induce pre-neoplastic lesions in the mammary gland of pregnant mice, apparently by directly targeting MaSCs and implicates BPA as an exogenous endocrine factor that may promote pregnancy-associated mammary tumorigenesis.
Citation Format: Bouamar H, Zhang F, Gu X, Dong Q, Sun L. Bisphenol A treatment induces hyperplasia in primary and stem cell-generated mammary glands from pregnant mice [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-02.
Abstract P6-07-03: Long non-coding RNA H19 promotes cancer stemness and worsen breast cancer survival
Authors: Shima H , Kida K , Yamada A , Sugae S , Narui K , Miyagi Y , Ryo A , Ichikawa Y , Ishikawa T , Endo I 
Published: February 2018

Abstract
Background: Cancer stem cells (CSC) are good sources of tumor initiation, heterogeneity, progression, and metastasis because of their unique characteristics. Several potential markers for CSCs have been suggested for breast cancer, including CD44+/CD24−/low, aldehyde dehydrogenase 1 (ALDH1), and epithelial cell adhesion molecule/epithelial-specific antigen. We previously reported that ALDH1 gene expression is related to aggressive phenotypes and poor prognosis in breast cancers. In this study, we conducted differential analysis of mRNA expression in ALDH1-positive breast cancer to identify genes associated with CSC. Next, we performed basic and clinical studies of one gene.
Methods: Messenger RNA was isolated from ALDH1-positive cells and ALDH1-negative cells in 5 ALDH1-positive breast cancers. Microarray analysis revealed that several genes were significantly associated with the ALDH1 gene. Among them, we examined a long non-coding RNA of H19 in this study. We evaluated the effect of H19 on CSCs using RNA interference and a sphere formation assay using two cell lines, HCC1937 and iCSCL10A cells. We also investigated H19 expression in 192 surgical specimens by in situ hybridization and analyzed the relationship between H19 expression and clinic pathological findings in breast cancer patients.
Results: Through in vitro experiments, we confirmed that suppression of H19 reduced sphere formation in both HCC1937 and iCSCL10A cells. Among surgical specimens, 48 samples (25%) expressed H19. We verified thatH19 positivity was significantly higher in ALDH1-positive cases than in ALDH1-negative cases (68% vs 9.7%, p &lt; 0.001). H19 was significantly highly expressed in triple-negative breast cancer (TNBC) (46%) compared with other subtypes: luminal (33%), luminal-HER2 (6%), and HER2-enriched subtype (15%). H19-positive patients showed significantly worse prognosis (5-year disease-free survival 75.8% vs 91.5%, p = 0.001 and 5-year overall survival 88.7% vs 97.7%, p = 0.002). The effect of H19 expression on prognosis was the most significant in TNBC compared to in other subtypes (5-year disease-free survival 63.6% vs 88.9%, p = 0.038).
Conclusions: H19 is clearly associated with CSCs and correlated with poor prognosis in breast cancer patients, particularly TNBC. Our future studies will investigate the role of H19 in maintaining the nature of CSCs and protein-coding genes associated with H19.
Citation Format: Shima H, Kida K, Yamada A, Sugae S, Narui K, Miyagi Y, Ryo A, Ichikawa Y, Ishikawa T, Endo I. Long non-coding RNA H19 promotes cancer stemness and worsen breast cancer survival [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-03.
Abstract P6-09-06: The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast: An analysis from the National cancer data base
Authors: Lewis GD , Xing Y , Patel T , Schwartz M , Rodriguez AA , Chen AC , Farach A , Hatch SS , Butler EB , Chang JC , Teh BS 
Published: February 2018

Abstract
Purpose/Objectives: Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer, accounting for &lt;2% of all cases. Previous studies demonstrated that this subtype often presents with hormone receptor (HR) positive disease, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to the availability of HER2 testing. In this study, we aim to determine the impact of molecular marker status (including HER2 status) on survival outcomes of invasive micropapillary carcinoma.
Materials/Methods: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC diagnosed from 2007-2012. Only patients with known estrogen receptor (ER) status, progesterone receptor (PR) status and HER2 status were included in the analysis. Cox multivariate regression was used to determine prognostic factors.
Results: Overall, 865 patients met inclusion criteria. The median follow-up was 2.5 years. Out of all patients, 651 (75.3%) had HR+, HER2 negative disease, 128 (14.8%) had HR+, HER2+ disease, 41 (4.7%) had HR negative, HER2+ disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated/undifferentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio 7.28, P&lt;0.001). Other prognostic factors associated with worse overall survival included African American descent (hazard ratio 2.24, P=0.018), comorbidity score of 1 (hazard ratio 2.50, P=0.011), comorbidity score ≥2 (hazard ratio 3.27, P=0.06), and ≥3 positive lymph nodes (hazard ratio 3.23, P=0.007).
Conclusions: Similar to invasive ductal carcinoma, triple negative disease in invasive micropapillary carcinoma results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in IMPC patients, as well as its impact on survival outcomes.
Citation Format: Lewis GD, Xing Y, Patel T, Schwartz M, Rodriguez AA, Chen AC, Farach A, Hatch SS, Butler EB, Chang JC, Teh BS. The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast: An analysis from the National cancer data base [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-06.
Abstract P6-15-01: Withdrawn
Authors: Loibl S , Untch M , Denkert C , Huober J , Blohmer JU , Grischke E-M , Furlanetto J , Tesch H , Hanusch C , Rezai M , Jackisch C , Schmitt WD , von Minckwitz G , Thomalla J , Kümmel S , Rautenberg B , Fasching PA , Rhiem K , Burchardi N , Schneeweiss A 
Published: February 2018

Abstract
This abstract was withdrawn by the authors.
Abstract PD4-02: Advantageous polypharmacology of abemaciclib revealed by omics profiling of CDK4/6 inhibitors
Authors: Hafner M , Mills CE , Subramanian K , Chen C , Boswell SA , Everley RA , Juric D , Sorger PK 
Published: February 2018

Abstract
Small molecule inhibitors of cyclin-dependent kinases (CDK) 4/6 have created new opportunities for the treatment of advanced hormone-receptor positive (HR+) breast cancer and show promise in other malignancies. Three CDK4/6 inhibitors, palbociclib (PD0332991; Ibrance), ribociclib (LEE011; Kisqali), and abemaciclib (LY2835219), which have been approved or are in late stage trials, are reported to be broadly similar although recent data suggest that abemaciclib has distinct single-agent activity in patients and a unique adverse effects profile. Differences in pharmacokinetics and relative potency for CDK4 versus CDK6 are postulated to account for these differences. In this paper, we use molecular and functional profiling by mRNA sequencing, mass spectrometry-based proteomics, and GR-based dose-response assays to obtain complementary views of the mechanisms of action of CDK4/6 inhibitors. We show that abemaciclib, but not ribociclib or palbociclib, is a potent inhibitor of kinases other than CDK4/6, including CDK1/Cyclin B, which appears to cause arrest in the G2 phase of the cell cycle, and CDK2/Cyclin E/A, which is implicated in resistance to palbociclib. Whereas ribociclib and palbociclib induce cytostasis, and cells adapt to these drugs within 2-3 days of exposure, abemaciclib induces cell death and durably blocks cell proliferation. Abemaciclib is active even in retinoblastoma protein (pRb)-deficient cells in which CDK4/6 inhibition by palbociclib or ribociclib is completely ineffective. The degree of polypharmacology of small molecule drugs is increasingly viewed as an important consideration in their design, with implications for efficacy, toxicity, and acquired resistance. In the case of CDK4/6 inhibitors, we propose that abemaciclib polypharmacology elicits unique molecular responses that are likely to be therapeutically advantageous. More generally, we propose that multi-omic approaches are required to fully elucidate the spectrum of targets relevant to drug action in tumor cells. We expect such understanding to assist in stratifying patient populations and ordering sequential therapies when resistance arises.
Citation Format: Hafner M, Mills CE, Subramanian K, Chen C, Boswell SA, Everley RA, Juric D, Sorger PK. Advantageous polypharmacology of abemaciclib revealed by omics profiling of CDK4/6 inhibitors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD4-02.
Abstract PD4-09: Combination FGFR4 and ER-targeted therapy for invasive lobular carcinoma
Authors: Levine KM , Chen J , Sikora MJ , Tasdemir N , Priedigkeit N , Tseng GC , Puhalla SL , Jankowitz RC , Dabbs DJ , McAuliffe PF , Lee AV , Oesterreich S 
Published: February 2018

Abstract
Background
Invasive Lobular Carcinoma (ILC) is an understudied subtype of breast cancer that requires novel therapies in the advanced setting. Distinctive properties of ILC include growth patterns, metastatic behavior, and receptor status (almost universally estrogen receptor (ER) positive). Our lab recently generated six long-term estrogen deprivation (LTED) models of ILC cells and performed RNA-Sequencing to identify differentially expressed genes compared to their parental cells cultured with estrogen. We overlapped these results with a previously published microarray dataset and found that FGFR4 is the most consistently overexpressed gene in the setting of acquired resistance to endocrine therapy in ILC cells.
Hypothesis
FGFR4 is an important mediator of resistance to endocrine therapy in ILC.
Methods
To study the role of FGFR4 in vitro, we used multiple shRNAs and specific small molecule inhibition for growth assays of ILC cells. To study the role of FGFR4 in de novo resistance to endocrine therapy, we collected 129 well curated ER+ ILC tumor specimens and performed gene expression analysis on the pre-treatment samples using a custom NanoString panel. To study the role of FGFR4 in acquired resistance, we collected over 50 pairs of primary-metastatic ER+ tumors and performed exon capture based RNA-Sequencing.
Results
FGFR4 inhibition decreases parental and LTED ILC cell growth in classic 2D conditions, in the setting of ultra-low attachment, and in colony formation assays. The LTED cells, with higher FGFR4 expression, are more sensitive to its inhibition. For the parental cells, combination FGFR4 and ER-targeting drugs results in synergistic decreases in growth. In our database of primary ILC clinical samples, increased expression of FGFR4 is predictive of shorter time to distant recurrence. For our collection of 50 paired, primary-metastatic ER+ tissues, FGFR4 expression increases on average &gt;2.5 fold in the metastatic setting, with large gains even in ductal carcinoma cases. Finally, in analyzing recently published cohorts of metastatic tumors, there is a significant enrichment of hotspot FGFR4 mutations in tumors originating in the breast, with &gt;2% of metastatic ILC tumors containing such a mutation.
Conclusion
FGFR4 may play an important role in both acquired and de novo resistance to endocrine therapy in ILC.
Citation Format: Levine KM, Chen J, Sikora MJ, Tasdemir N, Priedigkeit N, Tseng GC, Puhalla SL, Jankowitz RC, Dabbs DJ, McAuliffe PF, Lee AV, Oesterreich S. Combination FGFR4 and ER-targeted therapy for invasive lobular carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD4-09.
Abstract PD8-11: APOBEC3 contributes to mutational load in breast cancer
Authors: Zhao W , Peng Y , Mills GB , Peng G 
Published: February 2018

Abstract
Breast cancer results in large part from the accumulation of multiple mutations in premalignant cells, which provide a molecular basis for genetic diversity. This genetic diversity in premalignant cells allows selection for increased proliferation and survival and ultimately leads to invasion, metastasis, and therapeutic resistance. Recent genome-wide sequencing data showed that APOBEC3B (A3B) contributes to mutational load in breast cancer. A3B, a DNA cytosine deaminase, is overexpressed in more than 50% of breast tumors and more than 75% of breast cancer cell lines. Its overexpression and aberrant activation lead to unexpected clusters of mutations in the majority of breast cancers. This phenomenon of clustered mutations, termed kataegis (shower in Greek) forms a unique mutation signature in breast cancer. On the basis of the finding that A3B is a key molecular determinant of the mutator phenotype in breast cancer, the goal of our research is to utilize informatics tools to systematically characterize genetic alterations of APOBEC3 family proteins in breast cancer genomic data and define the molecular impact of altered APOBEC3 family proteins on mutability and anti-tumor immunity.
Our data showed that the mutation rate and copy number amplification/deletion of APOBEC3 genes are low. The levels of APOBEC3A (A3A) and A3B are highly correlated and are highest in Basal subtype and lowest in Luminal A tumors, in concordance with the proliferation of subtypes. Additionally, A3A and A3B are significantly correlated with total mutational load as well as with TP53 mutation, and with somatic copy number alterations (SCNA), especially focal SCNA. Among APOBEC3 genes, A3B is significantly associated DNA replication, DNA damage repair, cell cycle and proteasome signatures, and shows predictive and prognostic capacity in ER-positive patients. Interestingly, A3G expression is strongly associated with immune response signature genes in all breast tumors. Consequently, A3G is highly associated with tumor-infiltrating lymphocytes in breast and several other disease types.
In summary, our data demonstrate distinct expression pattern of APOBEC3 genes in different breast cancer subpopulations. Overexpression of different APOBEC3 family members leads to distinct molecular consequences. These data provide new molecular insights into pathophysiological functions of APOBEC3 genes in breast cancer and provide therapeutic opportunities for the breast cancer patients whose tumors have altered APOBEC3 expression levels and potentially are driven by APOBEC3 genes. Importantly, APOBEC3G is associated with evidence of immune activation that may signal responsiveness to immune checkpoint inhibitors.
Citation Format: Zhao W, Peng Y, Mills GB, Peng G. APOBEC3 contributes to mutational load in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD8-11.