bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-02-14: Circulating cell-free DNA (CFD) measured by a simple fluorescent assay to predict relapse in triple negative breast cancer patients receiving neoadjuvant chemotherapy: A biomarker substudy of prospective observational study (NCT02001519, NCT02001506)
Authors: Park K , Woo M , Kim JE , Ahn J-H , Jung KH , Kim S-B 
Published: March 2017

Abstract
Background: Prior technique to measure cell free DNA(CFD) is labor-intensive and expensive, while, recently developed fluorescent CFD assay is more simple and convenient.The aim of this study was to evaluate the role of CFD measured by a fluorescent assay as a biomarker of patients with triple negative breast cancer (TNBC) received neoadjuvant chemotherapy
Methods: We prospectively enrolled patients with TNBC, clinical stage II or III (T&gt;1.5cm or lymph node &gt; 1.5cm), who were scheduled for neoadjuvant chemotherapy. Patients received 4 cycles of adriamycin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (AC) followed by 4 cycles of cisplatin or docetaxel, and surgery. Plasma samples were obtained from patients before initial chemotherapy (baseline-CFD) and after 4 cycles of AC neoadjuvant chemotherapy (AC-CFD).
Results: This study included 72 patients who met the inclusion criteria. The mean levels of baseline-CFD and AC-CFD were 239±68 ng/mL and 210±66 ng/mL, respectively, and the CFD level was significantly decreased after AC chemotherapy.( p=0.001) The baseline-CFD was not associated with initial tumor characteristics. (T stage 1-2 vs. 3, p=0.313; N stage 0 vs. 1-3, p=0.317) There was no statistically significant difference between patients with response (CR or PR) to AC chemotherapy and those without response in terms of baseline-CFD, AC-CFD, and change of CFD between two values. (p=0.814, p=0.839, p=0.927) With 33.6 months of median follow up, there were 18 cases of relapse. Relapsed group showed numerically higher level of baseline-CFD, although it was not statistically significant. (relapse, 259 ng/mL; non-relapse, 233 ng/mL; p=0.161) We performed a ROC curve analysis of baseline-CFD for relapse, and found an area under the curve of 0.62 (95% CI, 0.46-0.78) at 222 ng/mL. Patients with baseline-CFD above 222 showed higher relapses than those below 222. (HR, 2.75; 95% CI, 0.96-7.84; p = 0.059)
Conclusions: The baseline-CFD obtained using a simple and convenient fluorescent assay could predict relapse, suggesting baseline-CFD as a potential biomarker for risk stratification of TNBC.
Citation Format: Park K, Woo M, Kim JE, Ahn J-H, Jung KH, Kim S-B. Circulating cell-free DNA (CFD) measured by a simple fluorescent assay to predict relapse in triple negative breast cancer patients receiving neoadjuvant chemotherapy: A biomarker substudy of prospective observational study (NCT02001519, NCT02001506) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-14.
Abstract P1-04-08: Non-nuclear SUMO dynamics regulate mammary epithelial cell transformation
Authors: Karami S , Lin F-M , Kumar S , Ren J , Bahnassy S , Bawa-Khalfe T 
Published: March 2017

Abstract
Objective: The reversible SUMO-posttranslational modification of protein substrates regulates various cellular processes and consistently is important for normal cell physiology. Disruption of SUMO enzymatic components supports onset of various pathophysiological disorders, including cancer. Our recent study identified a splicing event that differentially modulates expression of 2 SENP7 isoforms. The novel SENP7 variant SENP7S is the predominant SUMO protease in normal mammary epithelia; however onset of precancerous ductal carcinoma in situ (DCIS) reduces SENP7S significantly and stays low in all breast cancer (BCa) subtypes. Inversely, the full-length SENP7L isoform is upregulated in BCa and directly leads to BCa metastasis. Unlike SENP7L, SENP7S isoform contribution to carcinogenesis is unclear. Our objective is to define the biological function of this novel deSUMOylase SENP7S in normal versus cancerous epithelial cells.
Results: Consistently with mRNA levels, protein levels of the 2 SENP7 isoforms are also inversely expressed in human BCa versus normal mammary epithelia. SENP7S is localized in the cytosol of MCF10-2A unlike other SUMO proteases including SENP7L that are predominantly nuclear enzymes. Beta-catenin and a component of the Beta-catenin destruction complex, Axin1 are substrates for SENP7S catalytic activity as in the absence of SENP7S, Beta-catenin and Axin 1 are both SUMOylated. Consistently, SENP7S regulates Beta-catenin signaling pathway. SUMOylated Axin1 loses its interaction with Beta-catenin, allowing the Beta-catenin to escape ubiquitylation and further proteasomal degradation. SUMOylated Beta-catenin translocates to the nucleus and activates multiple target genes that potentiate cell proliferation. Increase in cell proliferation and anchorage dependent growth of non-cancerous MCF10-2A cells was observed with inhibition of SENP7S. Additionally, SENP7S depletion potentiates anchorage independent growth of MCF10-2A with significantly greater number and size of spheroids. In comparison to the control. Loss of SENP7S also potentiates the self-renewal properties of the cells, indicative of mammary epithelial cell transformation.
Conclusion: SENP7S modulates Beta-catenin stability and signaling and consequently is critical for normal mammary epithelial cell physiology. Loss of SENP7S, as observed in DCIS, initiates mammary epithelial cell transformation.
Citation Format: Karami S, Lin F-M, Kumar S, Ren J, Bahnassy S, Bawa-Khalfe T. Non-nuclear SUMO dynamics regulate mammary epithelial cell transformation [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-04-08.
Abstract P1-08-08: Identification of tumor-promoting and tumor-inhibiting genes with age dependent expression in breast cancer patients
Authors: Gu X , Zhu H , Sun L 
Published: March 2017

Abstract
Age is the number one risk factor for breast cancer development. The breast cancer incidence rate increases with age, following beta distribution, which is approximately linear in range from 30 to 70 years old [1]. Transcriptome alterations have been shown to promote tumorigenesis for many types of cancers. Therefore, we hypothesize that the genes with altered expression during aging may promote breast cancer development and/or progression. Using The Cancer Genome Atlas data, we extracted whole transcriptome profiling data of matched normal tissues from 82 female patients with age at diagnosis and menopausal status available. First, we applied simple linear regression to study the association between gene expression level and age at diagnosis on all the 82 patients. 258 upregulated and 240 downregulated genes are identified, which are associated with age. Secondly, 493 upregulated and 254 downregulated genes are identified that are altered by menopause by comparing post-menopausal to pre-menopausal patients (FDR &lt; 0.05). Exclusion of these menopause affected genes from those genes affected by age (258 upregulated and 240 downregulated) results in 148 upregulated and 189 downregulated genes during aging. Thirdly, by comparing matched tumor and adjacent normal samples, 3356 upregulated and 3124 downregulated genes are found to be associated with tumorigenesis. Overlapping of tumorigenesis associated genes with age dependent genes result in 14 upregulated and 24 downregulated genes that are both age and tumorigenesis associated. This discovery is being validated with normal breast tissues from donors in GTEx cohort. Experimental manipulation of the upregulated genes in seven breast cancer cell lines, representing five subtypes of breast cancer, demonstrated their essential role in promoting tumor malignancy, suggesting the upregulation is not merely passenger event. In a large mixed cohort, this panel of genes have significant predictive value in relapse free survival of breast cancer patients.
Funding: CPRIT Research Training Award (RP140105); NIH R01CA192564
Reference:
Francesco Pompei and Richard Wilson (2001). Age Distribution of Cancer: The incidence Turnover at Old Age. Human and Ecological Risk Assessment: Vol. 7, No. 6, pp. 1619-1650.
Citation Format: Gu X, Zhu H, Sun L. Identification of tumor-promoting and tumor-inhibiting genes with age dependent expression in breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-08-08.
Abstract P1-10-05: Omitting radiotherapy in women ≥ 65 years with early breast cancer and favorable histopathology after breast-conserving surgery, sentinel node biopsy and adjuvant endocrine therapy is safe
Authors: Villman KKA , Wickberg Å , Killander F , Lindman H , Bjöhle J , Edlund P , Tennvall-Nittby L , Bachmeier K , Carlberg M , Blomqvist C , Ahlgren J , Liljegren G 
Published: March 2017

Abstract
Background: The benefit of radiotherapy in older women with endocrine responsive early breast cancer treated with breast-conserving surgery and endocrine therapy is unclear. The aim of this study was to verify if omission of radiotherapy in a predefined cohort of patients with good prognosis early breast cancer after breast conservation is safe.
Methods: Eligibility criteria were: consecutive patients with age ≥ 65 years, breast-conserving surgery (sector resection + sentinel node biopsy), clear margins, unifocal T 1 N0, Elston grade 1 and 2, estrogen receptor-positive. After informed consent adjuvant endocrine therapy, either tamoxifen or an aromatase inhibitor, was prescribed for 5 years. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer, recurrence-free survival (RFS) and overall survival (OS).
Results: Between 2006 and 2012, we included 603 women from 14 Swedish centers. Two patients did not fulfill the inclusion criteria and were excluded from the analysis. Median age was 71 years (range 65 to 90). At a median follow-up of 59 months (range 2 to 110) 13 IBTR (cumulative incidence at five years, 1.3% (95% CI, 0.6% to 2.7%), 4 regional recurrences (one combined with IBTR), 2 distant recurrences both without IBTR or regional recurrence and 11 contralateral breast cancers was observed. Twenty-nine patients were diagnosed with tumors of other origin. Seven of them were endometrial cancers. There were 39 deaths. Only one of the deaths (2.6%) was due to breast cancer and 11 (28.2%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.9% (95% CI, 91.4% to 95.7%).
Conclusion: This study demonstrates, with a median follow-up of 59 months, that breast-conserving surgery and endocrine therapy without radiotherapy is a safe treatment option in women with early breast cancer and favorable histopathology aged ≥ 65 years. The risk of IBTR is comparable to the risk of contralateral breast cancer. The low rate of breast cancer deaths indicates that breast cancer mortality is of secondary importance in this subset of women.
Citation Format: Villman KKA, Wickberg Å, Killander F, Lindman H, Bjöhle J, Edlund P, Tennvall-Nittby L, Bachmeier K, Carlberg M, Blomqvist C, Ahlgren J, Liljegren G. Omitting radiotherapy in women ≥ 65 years with early breast cancer and favorable histopathology after breast-conserving surgery, sentinel node biopsy and adjuvant endocrine therapy is safe [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-05.
Abstract P1-10-10: Risk factors of locoregional recurrence, locoregional failure pattern and role of postmastectomy radiotherapy for T1-2 breast cancers with 1-3 positive axillary lymph nodes
Authors: Wang S , Peng R , Jin J , Wang W , Song Y , Liu Y , Liu X , Yu Z , Fang H , Ren H , Li Y 
Published: March 2017

Abstract
This abstract was not presented at the symposium.
Abstract P1-11-13: Re-excision rate in breast conservation surgery after neoadjuvant chemotherapy
Authors: Song JH , Park JY , Choi JE , Bae YK , Lee SJ 
Published: March 2017

Abstract
Background : The goal of neoadjuvant chemotherapy is to reduce tumor size and convert mastectomy to breast-conservation surgery (BCS). In response to neoadjuvant chemotherapy, the regression rate and pattern of breast cancer is variable. And the re-excision rate to secure negative resection margin is reported limitedly in this case. The purpose of this study was to compare the re-excision rate and BCS success rate of patients who received and who did not received neoadjuvant chemotherapy.
Method : In this retrospective cohort study, between January 2009 and December 2012, total 256 women were included who had clinical T2 breast cancer and were planed to receive BCS as initial operation or neoadjuvant chemotherapy. Fifty-nine patients of them received neoadjuvant chemotherapy. Clinical data were collected including age, preoperative or initial clinical tumor size, mammographic microcalcifications, ultrasound multifocality and axillary nodal status, retrospectively. In the resected specimen from BCS, we reviewed the pathologic tumor size, multifocality, histologic type, hormone receptor and Her-2-neu status, ki67, DCIS and EIC component. The re-excision rate and BCS success rate were investigated. Univariate analysis and regression model were used for identify clinicopathologic factors associated with re-excision. To reduce the effect of selection bias, propensity score matching-based anaylsis was also performed.
Results : Of the 256 patients, 178 patients (90.4%, 178/197) received BCS finally in neoadjuvant group and 56 patients (94.9%, 56/59) in non-neoadjuvant group (p=0.406). There was no statistical difference in the re-excision rate between two groups (35.6% (21/59) in neoadjuvant group vs 34.0% (67/197) in non-neoadjuvant group, p=0.946). In propensity-matched cohorts (N=118), the re-excision rate was same in two groups (35.6% (21/59) in neoadjuvant group vs 35.6% (21/59) in non-neoadjuvant group, p=1.000). BCS success rate was higher in neoadjuvant group(94.9% 56/59) than non-neoadjuvant group (86.4%(51/59)), but there was no statistical difference (p=0.205). In this cohorts, clinicopathologic factors associated with re-excision were pathologic multifocality (OR=4.56, p=0.0142), high ki67 (≥50%) (OR=0.7, p=0.0243) and DCIS component (OR=2.67, p=0.0261) in logistic regression model.
Conclusion: This study showed neoadjuvant chemotherapy could increase the BCS success rate but could not decrease the re-excision rate. The re-excision rate is more associated with pathologic finding rather than effect of neoadjuvant chemotherapy.
Citation Format: Song JH, Park JY, Choi JE, Bae YK, Lee SJ. Re-excision rate in breast conservation surgery after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-11-13.
Abstract P2-03-07: Exome sequencing of human breast cancer tissues resistant to taxanes
Authors: Endo Y , Dong Y , Kondo N , Hato Y , Hisada T , Nishimoto M , Nishikawa S , Takahashi S , Toyama T 
Published: March 2017

Abstract
Background: Although taxanes are a mainstay of breast cancer treatment, some cases are resistant to these drugs. This is a crucial issue in breast cancer therapy. In the emerging era of next-generation sequencing, it is possible to obtain extensive genomic information on individual tumors in a very short time. Using this technology, it was reported that specific mutations might affect therapeutic efficacy and induce resistance to specific treatment.
Objective: The aim of this study was to investigate the mechanisms of taxane resistance using whole exon sequencing and expression analyses in human breast cancer tissues.
Materials and Methods: We selected six breast cancer patients whose tumors responded well to anthracycline treatment but suffered disease progression on taxane treatment. We then performed whole exon sequencing on these samples using HiSeq (Illumia). In this way, we identified somatic mutations of candidate genes considered to be instrumental for mediating resistance to taxanes. Next, we performed mRNA expression analyses of these candidate genes in a further 122 breast cancers treated with taxanes at our institute. Finally, we correlated mRNA expression levels of these genes with clinicopathological factors and prognosis.
Results: We identified 9 mutations common to all 6 patients analyzed in this study, and a further 16 mutations shared by 5 of them. Kaplan-Meier analyses showed that high level mRNA expression of 3 of these 25 genes was significantly associated with poorer disease-free survival. Moreover, high level mRNA expression of one of these three genes was significantly associated with worse overall survival. However, there were no significant correlations between expression levels of these three genes and any clinicopathologeical features.
Conclusion: Using next-generation sequencing, we have identified three candidate genes involved in resistance to taxane treatment in breast cancer. We are now analyzing the functional attributes of these three genes.
Citation Format: Endo Y, Dong Y, Kondo N, Hato Y, Hisada T, Nishimoto M, Nishikawa S, Takahashi S, Toyama T. Exome sequencing of human breast cancer tissues resistant to taxanes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-03-07.
Abstract P2-05-33: Refining the prognostic value of Ki67 biomarker by ataxia telangiectasia mutated (ATM) status in a retrospective study of early stage hormone receptor positive breast cancer
Authors: Feng X , Li H , Kornarga E , Dean M , Lees-Miller S , Riabowol K , Magliocco A , Morris D , Watson P , Enwere E , Bebb G , Paterson A 
Published: March 2017

Abstract
Purpose: The current study was designed to investigate the combined influence of ataxia telangiectasia mutated (ATM) and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (&lt; 4 cm) and fewer than four positive lymph nodes.
Methods: Formalin-fixed paraffin-embedded specimens of resected primary breast tumors from 532 patients diagnosed with early stage breast cancer were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using immunohistochemistry and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome.
Results: Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p=0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02).
Low Ki67/high ATM expression independently predicts favorable disease survival in a multivariate model in low Ki67 subgroup of ES-HPBC (Stage I-III)Variablesp valueHR (95%CI)Low Ki67/high ATM vs Low Ki67/low ATM0.020.36 (0.15-0.88)ize (T1/2 vs T3/4)0.010.16 (0.04-0.69)LN status (- vs +)0.140.49 (0.20-1.25)LVI (_- vs +)0.160.51 (0.20-1.31)Grade (1/2 vs 3)&lt;0.00010.28 (0.11-0.67)Age (&lt;65 vs &gt;65)0.010.26 (0.10-0.74)
Conclusions: These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC.
Citation Format: Feng X, Li H, Kornarga E, Dean M, Lees-Miller S, Riabowol K, Magliocco A, Morris D, Watson P, Enwere E, Bebb G, Paterson A. Refining the prognostic value of Ki67 biomarker by ataxia telangiectasia mutated (ATM) status in a retrospective study of early stage hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-33.
Abstract P2-08-05: Phase I/II trial of palbociclib in combination with bicalutamide for the treatment of androgen receptor (AR)+ metastatic breast cancer (MBC)
Authors: Gucalp A , Corben AD , Patil S , Feigin KN , Boyle LA , Hudis CA , Traina TA 
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract P2-14-03: Novel visualization tools to search ongoing clinical trials and track trial results for metastatic breast cancer
Authors: Kumar M , Kissoon K , Abdulai AR , De La Torre K , Flowers M , Cohen E , Colen S , Mercier JB , Hurlbert M 
Published: March 2017

Abstract
Metastatic breast cancer (MBC) remains a terminal illness and is the cause of virtually all breast cancer deaths. The median survival for patients with MBC in the US is approximately 3 years from time of stage IV diagnosis. People living with MBC are in urgent need of new treatment options once current therapies no longer keep the disease under control. Access to new treatments is often through clinical trials. We have developed a novel way to visualize active clinical trials and track trial results. Methods: Clinical trials were queried from Clinicaltrials.gov and the National Cancer Institute. Trials were categorized by breast cancer subtype, line of therapy, hallmark of cancer, sponsor, phase, sample size and compound. A bubble chart was created to display data triplets (x, y, z) corresponding to three continuous variables: x and y to define the position, and z, the radius of each bubble. In our example, x and y coordinates are optimized according to an algorithm that essentially balances the bubble's gravity (i.e., action of moving towards the center of the plot), friction (i.e., velocity decay) and charge (or repulsion/attraction force). This layout is frequently used for network visualization. In addition to x, y and z, it is possible to encode other information. Results: We identified 204 clinical trials actively recruiting patients with MBC. The current webpage (www.mbcalliance.org) displays clinical trial data from 204 clinical trials in six different ways. Trials actively recruiting patients will be updated quarterly. In addition to data triplets (x, y and z) we encoded other information about trials using a color code to add three additional dimensions: phase, breast cancer subtype and sponsor type. When a user hovers over a bubble, key information about the clinical trial extracted from Clinicaltrials.gov is displayed. When a user clicks on the bubble, the user is directed to the corresponding landing page at BreastCancerTrials.org to access detailed trial information. We are employing a similar coding scheme and display characteristics for completed clinical trials results. Conclusions: We have developed a user-friendly, web tool to quickly sort and visualize ongoing clinical trials and results for completed trials to benefit both MBC patients and research scientists.
Citation Format: Kumar M, Kissoon K, Abdulai AR, De La Torre K, Flowers M, Cohen E, Colen S, Mercier JB, Hurlbert M. Novel visualization tools to search ongoing clinical trials and track trial results for metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-14-03.