Poster Session Abstracts最新文献

{"title":"Abstract P3-03-29: Evaluation of a direct reverse transcription loop-mediated isothermal amplification method without RNA extraction (direct RT-LAMP) for the detection of lymph node metastasis in early breast cancer","authors":"Ih Lee, J. Jung, S. Lee, J. Lee, R. Lee, H. Park, J. Kang, Y. Chae","doi":"10.1158/1538-7445.SABCS18-P3-03-29","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P3-03-29","url":null,"abstract":"Backgroud: The detection of lymph node metastasis by reverse transcription loop-mediated isothermal amplification method (RT-LAMP) had been studied previously. Even though, RT-LAMP method provides improved performance compared to intraoperative histology sentinel lymph node (SLN) evaluation, direct RT-LAMP method without RNA extraction can be more efficient and easily accessible process. Therefore, we evaluated the performance and efficacy of a direct reverse transcription loop-mediated isothermal amplification (direct RT-LAMP) assay for visual detection of CK19 , CK20 , and CEA mRNAs to identify lymph node metastasis in patients with early breast cancer. Methods: A total of 92 lymph nodes dissected from 40 patients with breast cancer were collected at the breast cancer center of Kyungpook National University Chilgok Hospital between November 2015 and February 2016. All of the samples were analyzed by direct RT-LAMP assay and routine histopathology examination. Cutoff values to distinguish metastasis and nonmetasis were determined by measuring cytokerain 19 (CK19) mRNA in histopathologically positive and negative lymph node using direct RT-LAMP. Results: We set the cutoff value of direct RT-LAMP assay for CK 19 mRNA at 1ng to distinguish status of LN metastasis. The sensitivity and specificity of the RT-LAMP assay were 85.7% and 100%, respectively. The positive predictive value and negative predictive value were 100% and 94.4%. Conclusion: Direct RT-LAMP assay can allow detection of SLN metastasis in breast cancer patients intraoperatively with a good sensitivity through cost-effective and time–saving manner. Citation Format: Lee IH, Jung J, Lee S, Lee J, Lee RK, Park H, Jung J, Kang J, Chae Y. Evaluation of a direct reverse transcription loop-mediated isothermal amplification method without RNA extraction (direct RT-LAMP) for the detection of lymph node metastasis in early breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-29.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74654261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P6-21-01: Xentuzumab (BI 836845), an insulin-like growth factor (IGF)-neutralizing antibody (Ab), combined with exemestane and everolimus in hormone receptor-positive (HR+) locally advanced/metastatic breast cancer (LA/mBC): Randomized phase 2 results","authors":"J. Crown, M. Sablin, J. Cortes, J. Bergh, S. Im, Y. Lu, N. Martínez, P. Neven, K. Lee, S. Morales, J. Pérez-Fidalgo, D. Adamson, A. Gonçalves, A. Prat, G. Jerusalem, L. Schlieker, R. Espadero, T. Bogenrieder, D. Huang, P. Schmid","doi":"10.1158/1538-7445.SABCS18-P6-21-01","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P6-21-01","url":null,"abstract":"Background: Xentuzumab (Xen), an IGF-1/-2-neutralizing Ab, binds IGF-1 and IGF-2, inhibits their growth-promoting signaling, and suppresses AKT activation by everolimus (Ev). This Phase 1b/2 trial evaluates Xen in combination with Ev and exemestane (Ex) in HR+/HER2− LA/mBC. Methods: The two-arm, open-label, randomized Phase 2 part enrolled female patients (pts) with HR+/HER2− LA/mBC not amenable to curative therapy and refractory to nonsteroidal aromatase inhibitors. Pts were randomized (1:1) to: oral Ev (10 mg/d) + Ex (25 mg/d); or Xen (1000 mg/wk iv) + Ev (10 mg/d) + Ex (25 mg/d). Randomization was stratified by visceral metastases (VM; Y vs N). Treatment continued in 28-day cycles until progression, intolerable adverse events (AEs) or other reasons for discontinuation. Primary endpoint was progression-free survival (PFS), with an interim futility analysis incorporated in the study design. Results: Following the results of the interim analysis, the Data Monitoring Committee (DMC) advised early termination of the trial and discontinuation of Xen treatment. Thus, Xen treatment exposure time and time-to-event data for the Xen+Ev+Ex arm are limited. Of the 139 women treated (Xen+Ev+Ex 70; Ev+Ex 69), 77% had VM. Median PFS was not significantly different between arms (Xen+Ev+Ex vs Ev+Ex, 7.3 vs 5.6 months; HR [95% CI] 0.97 [0.57–1.65]; p=0.91). In a pre-specified subgroup of pts without VM, Xen+Ev+Ex showed favorable PFS vs Ev+Ex (HR 0.21 [0.05–0.98]; Pint=0.0141). Pint values Conclusion: In the overall population, PFS did not improve with the addition of Xen to Ev+Ex and the trial was therefore discontinued early. Nevertheless, a favorable signal was observed in the pre-specified subgroup of pts without VM when treated with Xen+Ev+Ex, which warrants additional investigation. The safety profile was comparable between arms. Citation Format: Crown J, Sablin M-P, Cortes J, Bergh J, Im S-A, Lu Y-S, Martinez N, Neven P, Lee KS, Morales S, Perez-Fidalgo JA, Adamson D, Goncalves A, Prat A, Jerusalem G, Schlieker L, Espadero R-M, Bogenrieder T, Chin-Lun Huang D, Schmid P. Xentuzumab (BI 836845), an insulin-like growth factor (IGF)-neutralizing antibody (Ab), combined with exemestane and everolimus in hormone receptor-positive (HR+) locally advanced/metastatic breast cancer (LA/mBC): Randomized phase 2 results [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-21-01.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74931322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P5-05-02: Thyroid hormone replacement therapy shortens survival in hormone receptor positive early stage breast cancers","authors":"Reema S Wahdan-Alaswad, S. Edgerton, Hs Salem, Bolin Liu, A. Thor","doi":"10.1158/1538-7445.SABCS18-P5-05-02","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P5-05-02","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72954946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P4-06-24: Microenvironment heterogeneity of triple-negative breast cancer reveals distinct immune escape mechanisms and potential driver events","authors":"Yi Xiao, D. Ma, Shimin Zhao, Y-Z Jiang, Z. Shao","doi":"10.1158/1538-7445.SABCS18-P4-06-24","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P4-06-24","url":null,"abstract":"Background The microenvironment phenotypes strongly affect the immunotherapeutic strategies for triple-negative breast cancer (TNBC). Although the multi-omics profile of TNBC has been comprehensively characterized, few studies have focused on the microenvironment phenotypes of TNBC. Methods With multi-omics data for the largest single-center TNBC cohort (n=386), we first established a TNBC-specific microenvironment cell signature. We further used single sample gene set enrichment analysis to calculate the relative number of microenvironment cell subsets in each sample. Then, we performed k-means clustering to classify the TNBC microenvironment phenotypes into heterogeneous clusters. Furthermore, we systematically analyzed the extrinsic and intrinsic immune escape mechanisms of different TNBC microenvironment clusters. In addition, we explored genomic alterations that might decrease immune infiltration in certain TNBC microenvironment clusters. Results We classified the TNBC microenvironment phenotypes into three heterogeneous clusters. Cluster 1 (type 1 “cold tumor”) had low microenvironment cells infiltration. Cluster 2 (type 2 “cold tumor”) was characterized by resting innate immune cells, fibroblasts and endothelial cells infiltration. Cluster 3 (“hot tumor”) was featured by adaptive immune cells infiltration. Analysis of immune escape mechanism revealed that an incapability to attract innate immune cells (resulting in failure of adaptive immunity) led to immune escape of cluster 1. The chemotaxis but inactivation of innate immunity (also leading to failure of adaptive immunity) and low tumor antigen burden resulted in immune escape of cluster 2. High expression of immune checkpoint molecules contributed to immune escape of cluster 3. In addition, we found that tumor infiltrating lymphocytes (TILs) were positively correlated with immune checkpoint molecules expression, while mutation load was negatively correlated with those indicators in triple-negative breast cancer. Analysis of enrichment pathways, mutations and somatic copy number variations between the “cold tumor” and “hot tumor” clusters revealed that amplification of MYC and activation of MYC-related pathways might decrease the immune infiltration of cluster 1. Mutations in PI3K-AKT pathway members and activation of fibroblasts-related pathways might decrease the immune infiltration of cluster 2. Conclusion Utilizing the largest single-center TNBC cohort with multi-omics data, our study first revealed the heterogeneity of the TNBC microenvironment, with translational significance both clinically and biologically. First, we identified a subtype of “hot tumor” in TNBC (cluster 3), for which immune checkpoint blockers (ICBs) might be effective. TILs and immune checkpoint molecules expression but not mutation load might predict the efficacy of ICBs. Second, we presumed some genomic alterations that might drive “cold tumor” formation in TNBC. Our study represents a step toward personalized ","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73432408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P6-07-02: The CARMA3-Bcl10-MALT1 signalosome mediates pro-angiogenic IL-6 and IL-8 paracrine signaling in GPCR+ breast cancer","authors":"Heejae Kang, P. Ekambaram, L. McAllister-Lucas, P. C. Lucas","doi":"10.1158/1538-7445.sabcs18-p6-07-02","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-p6-07-02","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75330978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P4-14-10: Withdrawn","authors":"M. Ekholm, P. Bendahl, M. Fernö, B. Nordenskjöld, O. Stål, L. Rydén","doi":"10.1158/1538-7445.SABCS18-P4-14-10","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P4-14-10","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75497465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P3-10-29: tRNA-derived fragments as novel predictive biomarkers for trastuzumab-resistant breast cancer","authors":"C. Sun, Wei Li, Hao Wu, Xue F. Huang, Jing Li, Z. Fu, J. Tang, Yuxin Yin","doi":"10.1158/1538-7445.sabcs18-p3-10-29","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-p3-10-29","url":null,"abstract":"Background: Resistance to trastuzumab remains a common challenge to HER-2 positive breast cancer. Up until now, the underlying mechanism of trastuzumab resistance is still unclear. tRNA-derived small non-coding RNAs, a new class of small non-coding RNA (sncRNAs), have been observed to play an important role in cancer progression. However, the relationship between tRNA-derived fragments and trastuzumab resistance is still unknown. Methods:We detected the levels of tRNA-derived fragments expression in normal breast epithelial cell lines, trastuzumab-sensitive and -resistant breast cancer cell linesusing high-throughput sequencing.qRT-PCR was conducted to validate the differentially expressed fragments in serums from trastuzumab-sensitive and -resistant patients. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the power of specific tRNA-derived fragments.Progression-free survival (PFS) was analyzed using Cox-regression. Results:Our sequence results showed that tRNA-derived fragments were differentially expressed in the HBL-100, SKBR3, and JIMT-1 cell lines. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were found significantly upregulated in trastuzumab-resistant patients compared to sensitive individuals, and the ROC analysis showed that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were correlated with trastuzumab resistance. In a multivariate analysis, higher levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression were associated with significantly shorter PFS in patients with metastatic HER-2 positive breast cancer. Conclusion: Our results suggest that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN play important roles in trastuzumab resistance. Patients with high levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression benefitted less from trastuzumab-based therapy than those that express lower-levels of these molecules. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN may be potential biomarkers and intervention targets in the clinical treatment of trastuzumab-resistant breast cancer. Citation Format: Sun C, Li W, Wu H, Huang X, Li J, Fu Z, Tang J, Yin Y. tRNA-derived fragments as novel predictive biomarkers for trastuzumab-resistant breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-10-29.","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73685177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P1-12-06: Endothelial dysfunction in breast cancer survivors on aromatase inhibitors (AIs) over time","authors":"A. Blaes, A. Petersen, H. Beckwith, D. Potter, Natalia D Florea, D. Yee, R. Vogel, D. Duprez","doi":"10.1158/1538-7445.sabcs18-p1-12-06","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-p1-12-06","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74223658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P1-12-17: Exercise and nutrition intervention on breast cancer survivors in Taiwan with BMI 25 or more to decrease BMI and maintain at an appropriate level -A preliminary report","authors":"C. Hsieh, N. Yang, A. Yang, C. Tseng","doi":"10.1158/1538-7445.sabcs18-p1-12-17","DOIUrl":"https://doi.org/10.1158/1538-7445.sabcs18-p1-12-17","url":null,"abstract":"","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72576295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract P6-18-19: Real-world survival of heavily pretreated patients with refractory HR+, HER2- metastatic breast cancer receiving single-agent chemotherapy - A comparison with MONARCH 1","authors":"H. Rugo, V. Diéras, J. Cortes, D. Patt, H. Wildiers, J. O’Shaughnessy, E. Zamora, D. Yardley, G. Carter, K. Sheffield, Liming Li, V. André, Re Derbyshire, Xi Li, Martin Frenzel, Y. Huang, M. Dickler, S. Tolaney","doi":"10.1158/1538-7445.SABCS18-P6-18-19","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-P6-18-19","url":null,"abstract":"Background In MONARCH 1 (NCT02102490), abemaciclib demonstrated promising single-agent activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2- metastatic breast cancer (MBC). 1 Confirmed objective response rate (ORR) was 19.7% (95% CI: 13.3, 27.5) and at 18 months minimum follow-up median overall survival (OS) was 22.3 months. Due to the single-arm trial design of MONARCH 1, there is a need to view these results in clinical context relative to available treatment options. This study compared the OS results of abemaciclib in MONARCH 1 vs that in a real-world single-agent chemotherapy cohort with similar patient and disease characteristics. Methods MONARCH 1 study design and key eligibility criteria were previously described. 1 The real-world cohort was based on Flatiron Health electronic health records-derived, nationally representative (USA-based) database comprising patient-level structured and unstructured data, curated via technology-enabled abstraction, for patients with MBC between January 1, 2011 through February 28, 2018. A real-world single-agent chemotherapy cohort was created based on the key eligibility criteria of MONARCH 1 and included patients diagnosed with HR+, HER2- MBC who received single-agent chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) following 1-2 prior chemotherapy regimens in the metastatic setting, had an ECOG PS of 0-1, and no prior CDK4 & 6 therapy. The index date was the start of the eligible single-agent chemotherapy, and patients were followed from the index date until date of death, loss to follow-up, or end of the database, whichever occurred earlier. OS results were adjusted using 2 methods (Mahalanobis distance matching and entropy balancing with bootstrapping) to account for baseline demographic and clinical differences between the real-world and trial cohorts. Results A real-world cohort (n=281) with eligibility criteria similar to the MONARCH 1 population (n=132) was identified. A subsequent matching based on Mahalanobis distance was performed to match MONARCH 1 population (n=108) with the real-world cohort (n=108). The matched cohorts demonstrated similar patient and disease characteristics. Median OS was 22.3 months in the abemaciclib arm vs 13.6 months in the matched cohort with an estimated hazard ratio (HR) of 0.54 (95% CI: 0.37, 0.77). Results of a sensitivity analysis performed using entropy balancing were consistent with an adjusted median OS of 12.7 months in the real-world cohort (n=281)with HR of 0.57 (95% CI from bootstrapping: 0.44, 0.78). Conclusion Methodological advances to adjust for potential biases, and improvements in data quality, have evolved enabling the ability to leverage a real-world cohort as an external comparator arm. This study demonstrates the ability to create a real-world chemotherapy cohort suitable to serve as a comparator for MONARCH 1. These exploratory results suggest a survival advantage and adequately place ","PeriodicalId":20307,"journal":{"name":"Poster Session Abstracts","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74559760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}