bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-06-04: The power of next generation sequencing in the detection of breast and ovarian cancer susceptibility genes other than BRCA
Authors: Eliade M , Skrypski J , Baurand A , Jacquot C , Bertolone G , Loustalot C , Coutant C , Guy F , Fumoleau P , Rivière J-B , Duffourd Y , Ghiringhelli F , Végran F , Boidot R , Lizard S , Faivre L 
Published: May 2016

Abstract
Background : Most cases of breast and ovarian cancer susceptibility remains unexplained. Testing multiple genes in one go with next generation sequencing is then an asset with the recent discovery of new genes involved in breast and ovarian cancer susceptibility.
Methods : We studied 457 patients originated from Burgundy (France) fulfilling the criteria for BRCA1/2 testing using a next generation sequencing 25-gene panel including 17 genes of predisposition for breast and/or ovarian cancer (ATM, BARD1, BRCA 1/2, BRIP1, CHEK2, PALB2, RAD51C, TP53, PTEN, RAD50, MRE11, MLH1, MSH2, MSH6, PMS2, STK11).
Results : A pathogenic BRCA1/2 mutation was found in 8% (n=37) of patients. Besides, we found 39 deleterious or probably deleterious mutations in 13 different genes. The most frequently mutated genes were CHEK2 (n=10 ; 2.1 %), ATM (n=9 ; 2 %), and PALB2 (n=4 ; 0.9%). One patient had deleterious mutations in both TP53 and PALB2, and another one had deleterious mutations in both BRCA2 and CHEK2. The mutation could explain the phenotype in the majority of cases, but a pathogenic mutation was found in a different predisposing gene in 7 patients, and could be considered as incidental findings with the currently published spectrum of cancer locations.
Conclusion : Besides BRCA1/2 mutations, that remain the most frequent susceptibility genes for breast and ovarian cancer, gene panels remain a powerful tool for identifying the other less frequent susceptibility genes. The penetrance and spectrum of cancer associated to these other genes remain sometimes undefined, and further collaborative work is crucially needed to address this question. The possibility of double hits should led to careful genetic counseling.
Citation Format: Eliade M, Skrypski J, Baurand A, Jacquot C, Bertolone G, Loustalot C, Coutant C, Guy F, Fumoleau P, Rivière J-B, Duffourd Y, Ghiringhelli F, Végran F, Boidot R, Lizard S, Faivre L. The power of next generation sequencing in the detection of breast and ovarian cancer susceptibility genes other than BRCA. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-06-04.
Abstract P2-06-07: PRKCQ regulates taxol sensitivity of triple negative breast cancer cells via IL-6/Stat3 signaling
Authors: Irie HY , Byerly J 
Published: May 2016

Abstract
Background/Rationale. While some patients with triple negative breast cancer achieve long-term remission with chemotherapy, many have cancers that are chemotherapy resistant. The lack of targeted therapies for this subtype also makes some triple negative cancers difficult to treat and control. PRKCQ, a member of the novel protein kinase C family, is preferentially expressed in triple negative breast cancers compared to ER+/Luminal cancers. We previously reported that PRKCQ expression drives growth-factor independent growth, anoikis resistance and migration of breast epithelial cells. In addition, PRKCQ is required for in vivo growth of triple negative breast cancers tumor xenografts. We sought to determine if PRKCQ expression modulates sensitivity of triple negative breast cancer cells to standard of care chemotherapy and whether PRKCQ inhibition could be a strategy to induce death of chemotherapy-resistant triple negative breast cancer cells. Methods. We determined the effects of modulating PRKCQ expression, using PRKCQ cDNA or shRNA vectors, on Doxorubicin or Taxol treatment-induced effects on triple negative breast cancer cells, including those that are relatively chemotherapy resistant at baseline. We determined the mechanisms by which PRKCQ expression regulates sensitivity to Taxol. Results. Increased PRKCQ expression in MCF-10A breast epithelial cells suppresses the apoptosis-inducing effects of Doxorubicin or Taxol treatment. PRKCQ-induced Taxol resistance is dependent on PRKCQ kinase activity. PRKCQ-expressing MCF-10A cells secrete enhanced levels of IL-6, leading to the autocrine activation of Stat3; IL-6/Stat3 activation is necessary for PRKCQ-induced resistance to Taxol. Finally, downregulation of PRKCQ sensitized MDA-231-Luc cells to Taxol treatment and induced apoptosis of these cells which are relatively resistant to Taxol at baseline. Conclusions. PRKCQ regulates sensitivity to standard of care chemotherapies used in the treatment of triple negative breast cancer. IL-6/Stat3 signaling induced by PRKCQ kinase activity is responsible for resistance to the effects of Taxol treatment. Targeting PRKCQ therefore could be an attractive strategy to overcome chemotherapy resistance of a subset of triple negative breast cancers.
Citation Format: Irie HY, Byerly J. PRKCQ regulates taxol sensitivity of triple negative breast cancer cells via IL-6/Stat3 signaling. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-06-07.
Abstract P2-08-26: Tumor-associated macrophages and platelet-derived growth factor C as a prognostic marker for breast cancer patients
Authors: Yoo T-K , Lee K-M , Jung H , Na YR , Seok SH , Han W 
Published: May 2016

Abstract
Introduction: Tumor related inflammation plays an important role in breast cancer progression, tumor-associated macrophages (TAMs) being a crucial part of this microenvironment. Platelet-derived growth factor-C (PDGF-C) is abundant in the breast cancer microenvironment having an anti-apoptotic effect on macrophages. Previous reports suggest that tumor cell derived PDGF-C promotes TAM survival, enhancing tumor progression. In this study we analyzed the prognostic value of PDGF-C density associated with TAM infiltration in human breast cancer.
Materials and Methods: TAM and PDGF-C density was evaluated by immunohistochemistry of CD163+, CD68+ and PDGF-C myeloid cells in tumor stroma. Tissue microarrays from 140 invasive breast cancer cases were used. Survival analysis to evaluate the impact of TAM and PDGF-C density on disease free survival (DFS) was done using Kaplan-Meier and Cox regression analysis.
Results: Infiltration of CD163+ and CD68+ macrophages into tumor stroma had a tendency, but not significant, for reduced DFS (p=0.204, p=0.314 respectively). Whereas PDGF-C strong density was significantly associated with worse DFS (p=0.024). This inverse correlation with DFS was demonstrated stronger when PDGF-C density was combined with CD163+ and CD68+ macrophage infiltration (p=0.008, p=0.018, respectively). But, CD163+ or CD68+ infiltration with strong PDGF-C density did not demonstrate as an independent prognostic factor when adjusting for tumor size, lymph node metastasis, hormone receptor and histologic grade. This result is probably due to small number of patients having both TAM infiltration and strong PDGF-C density.
Conclusion: Our results show that PDGF-C infiltration adversely affects DFS and also enhances the inverse correlation between tumor-associated macrophages and DFS. To support these results, a study with larger numbers is on progress.
Citation Format: Yoo T-K, Lee K-M, Jung H, Na YR, Seok SH, Han W. Tumor-associated macrophages and platelet-derived growth factor C as a prognostic marker for breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-26.
Abstract P3-03-01: Intracranial PDX models of breast cancer metastasis
Authors: Nielsen CH , Nedergaard MK , Wick MJ , Papadopoulos K , Tolcher AW , Kjaer A 
Published: May 2016

Abstract
Background: Overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cancer is an independent factor for development of brain metastases. Up to 37% of patients with HER2 positive disease relapse intracranially despite control of extra-cranial metastatic disease. Inability of anti-cancer agents to cross an intact blood-brain barrier (BBB) is a possible explanation for the increased incidence of brain metastases.
Subcutaneous (SQ) patient-derived xenograft (PDX) models are increasingly used for efficacy studies in drug development. However, orthotopic PDX models may confer a translational advantage as the patient tumor microenvironment is more closely mimicked. Especially when targeting brain tumors, the major impact of the BBB on drug bioavailability must be taken into consideration. The aim of this study was therefore to develop a panel of intracranial PDX models of breast cancer brain metastases for pre-clinical efficacy studies of new anticancer drugs.
Methods: SQ tumors from three different HER2 positive PDX breast cancer models designated ST340, ST1339 and ST1616B were enzymatically digested and used for intracranial stereotactic injection in nude mice. Contrast-enhanced T1- and T2-weighted Magnetic Resonance Imaging (MRI) were used to determine tumor take. Intracranial tumor growth was monitored using MRI and positron emission tomography (PET) in conjunction with the amino acid radio tracer 18F-FET.
Results: MRI confirmed tumor take in one model as early as 2 weeks after intracranial implantation. Increased 18F-FET uptake was detected in all models. MRI could be effectively used to monitor tumor growth and the corresponding 18F-FET PET images demonstrated increased 18F-FET uptake over time.
Conclusion: Three different HER2 positive intracranial PDX breast metastases models were established from low passage SQ PDX models. We suggest, that using these intracranial PDX models of brain metastases, new drugs for advanced breast cancer can be evaluated in preclinical models that more closely mimic the microenvironment and the BBB in patients. In addition, translational imaging techniques can be evaluated during preclinical testing and the potential of tracers like 18F-FET as imaging biomarkers of therapeutic response can be assessed. Together, the established SQ and orthotopic PDX models of breast cancer and brain metastases can be used as a relevant translational platform for testing of new drugs.
Citation Format: Nielsen CH, Nedergaard MK, Wick MJ, Papadopoulos K, Tolcher AW, Kjaer A. Intracranial PDX models of breast cancer metastasis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-03-01.
Abstract P3-07-21: Non-alcoholic fatty liver disease induced by selective estrogen receptor modulators is a protective factor for breast cancer survival
Authors: Wang S , Zheng Q , Nie M , Xu F , Xia W , Yuan Z , Peng R , An X , Qin T , Qin G 
Published: May 2016

Abstract
Purpose: Non-alcoholic fatty liver disease (NAFLD) induced by selective estrogen receptor modulators (SERMs) treatment may be related to treatment efficacy for the antagonism of circulating estrogens. We conducted a retrospective study to investigate the relationship between survival outcomes and NAFLD in breast cancer patients treated with tamoxifen or toremifene.
Patients and methods: 785 eligible patients received tamoxifen or toremifene in Sun Yat-sen university cancer center from January 2005 to December 2009 were included in our study. All patients have at less one abdominal ultrasonography measurement at baseline and every year's follow-up. Patients who diagnosed NAFLD by ultrasonography during three-year's follow-up were classified into NAFLD cohort, others were classified into no-NAFLD cohort. Univariate and multivariate Cox regression was utilized to analyse the relationship between NAFLD and disease-free survival (DFS) and overall survival (OS).
Results:158 patients had reported NAFLD in the first 3 years' follow-up. Patients who developed NAFLD had better DFS and OS than those not developing NAFLD. The 5-years DFS was 91.56% and 85.01% at NAFLD and no-NAFLD cohort (univariate hazard ratio [HR]: 0.59 [95%CI 0.37-0.96], P=0.034), respectively. The 5-years OS was 96.64% and 93.31% at NAFLD and no-NAFLD cohort (univariate HR: 0.39 [95%CI 0.16-0.99], P=0.047), respectively. Multivariate analysis revealed that NAFLD is an independent prognostic factor on DFS in breast cancer patients with SERMs treated. Women treated with SERMs experienced NAFLD in the first three-year's follow-up had a reduced risk of DFS of 42% (multivariate HR: 0.58; [95%CI 0.36-0.95], P=0.032) compared with patients without NAFLD.
Conclusion: NAFLD induced by SERMs seems to be associated with better survival outcomes and may therefore be helpful in predicting treatment responses in breast cancer patients treated with SERMs.
Citation Format: Wang S, Zheng Q, Nie M, Xu F, Xia W, Yuan Z, Peng R, An X, Qin T, Qin G. Non-alcoholic fatty liver disease induced by selective estrogen receptor modulators is a protective factor for breast cancer survival. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-21.
Abstract P3-07-24: The role of glucocorticoid receptor (GR) expression in predicting pathological complete response (pCR) to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC)
Authors: Saha P , Turk A , Lurain K , Baker G , Conzen S , Nanda R 
Published: May 2016

Abstract
Background
Up to 40% of breast cancers have moderate to strong expression of GR, and activation of GR is associated with poor prognosis in ER-negative breast cancer. GR activation in breast cancer cells initiates anti-apoptotic signaling, contributing to chemotherapy resistance. We hypothesize that GR highly expressing TNBCs will have a suboptimal response to neoadjuvant chemotherapy.
Methods
We identified patients with triple-negative breast cancer (TNBC) who received neoadjuvant chemotherapy at the University of Chicago between 2002 and 2014 under IRB approved protocols. Those patients for whom pre-treatment and post-treatment tissue was available were included in this study. Unstained sections of formalin-fixed paraffin-embedded primary tumor were obtained. Percentage tumor cell GR expression was determined via immunohistochemical (IHC) examination using two different antibodies: the anti-GR rabbit monoclonal XP antibody (Cell Signaling, D8H2, 1:500 dilution) and the polyclonal rabbit anti-GR antibody (1:80). Staining was performed according to methods previously published by Belova et al. TNBCs were considered GR positive if greater than 10% of cancer cells stained moderately to strongly positive for GR.
Results
Fifty paired tissue samples were identified and pre- and post-treatment tissue was stained for GR using two anti-GR antibodies as above. Of these 50 cases, 80% had moderate to strong expression of GR using the XP antibody; results with the polyclonal ab will be compared. Percentage GR expression did not change in the setting of treatment. Work to correlate GR expression using the monoclonal versus the polyclonal antibody and clinicopathological features is ongoing.
Conclusions
To our knowledge, this is the first study attempting to evaluate percentage GR expression as a biomarker of response to neoadjuvant chemotherapy in TNBC. If higher GR expression correlates with a lower pCR rate in TNBC as hypothesized, then GR blockade in conjunction with chemotherapy may overcome chemotherapy resistance and lead to improved response to treatment in patients with GR expressing TNBCs.
Citation Format: Saha P, Turk A, Lurain K, Baker G, Conzen S, Nanda R. The role of glucocorticoid receptor (GR) expression in predicting pathological complete response (pCR) to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-24.
Abstract P3-07-59: Stem cell markers are overexpressed in tumorspheres cultured from circulating epithelial tumor cells (CETCs) in patients with breast cancer
Authors: Zimon D , Pizon M , Mayer V , Pachmann K 
Published: May 2016

Abstract
Background:
Breast malignancies continuously shed tumor cells which may enter the circulation, spread to other tissue and initiate metastases, but only a small subpopulation among CETCs is capable of metastasis formation. The subpopulation of CETC capable of forming tumorspheres in vitro and carrying stem cells properties is assumed to have metastatic potential. The aim of this study was to characterize the pattern of expression of the tumorspheres as compared to CETCs.
Methods:
Blood samples were obtained from patients diagnosed with breast tumors. CETCs were enumerated with maintrac method and subsequently cultivated in stem cell-selective medium. The expression of stem cell marker genes EpCAM, Nanog, Okt4 Sox2, ALDH and CD133 were detected by RT-PCR in single CETCs and tumorspheres.
Results:
0.1- 10% of CETCs could form non-adherent tumorspheres under stem cell- selective conditions after a period of 14 days. Array qRT-PCR analysis revealed that putative stem cell markers, such as Oct4, Sox2, Nanog, EpCAM, ALDH1 and CD133 are overexpressed in relation to house-keeping genes RPL13a and GAPDH in tumor spheres in contrast to the significantly lower expression level of these stem cell markers in individually isolated CETCs. High expression level of pluripotency genes in tumorspheres was associated with aggressive tumor behaviour in terms of tumor progression and type of cancer.
Conclusion:
Thus, differential expression of stem cell markers in CETCs and tumorspheres substantiates the hypothesis that only a small population of circulating tumor cells possess the stem cell properties and are responsible for metastasis formation.
Citation Format: Zimon D, Pizon M, Mayer V, Pachmann K. Stem cell markers are overexpressed in tumorspheres cultured from circulating epithelial tumor cells (CETCs) in patients with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-59.
Abstract P3-07-60: Impact of high SPARC expression of a primary tumor as a strong risk factor for disease recurrence and overall survival in patients with triple-negative breast cancer
Authors: Zhu A , Yuan P , Du F , Ding X , Xu B 
Published: May 2016

Abstract
Background: SPARC (secreted protein acidic and rich in cystein) is a secreted glycoprotein that interacts with extracellular matrix protein and acts as a regulator of critical cellular functions such as proliferation and cell migration. An increasing number of studies have shown altered expression of SPARC in several malignancies. However, the role of this potential biomarker in breast cancer development and progression is controversial. Triple-negative breast cancer (TNBC) is known for its poor prognosis and high recurrence probability. There is a need for prognostic biomarkers to guide treatment decisions for this subtype.
Objective: To explore the association between SPARC and the prognosis of triple-negative breast cancer.
Methods: In this study, a total of 211 samples of triple-negative breast lesions from 2004 to 2008 were collected in Cancer Hospital, Chinese Academy of Medical Sciences. SPARC expression was evaluated by immunohistochemistry using an immunoreactive score (IRS) from patients with up to 10 years clinical follow-up data. The current study set out to examine both the expression of SPARC in primary tumor tissue and to demonstrate if a link existed between the levels of SPARC and the clinical outcome. Cox proportional hazards model was used to estimate HRs and 95%CI, stratified on tumor grade, TNM stage, lymph node status and vascular invasion.
Results: High SPARC expression (IRS≥3) was observed in 52.1% of all primary tumors. Patients expressing low levels of SPARC had better disease-free survival (DFS) (HR=0.632, 95%CI:0.405-0.987, P = 0.044) as well as overall survival(OS)(HR=0.576, 95%CI:0.351-0.946, P = 0.029) compared to those with high SPARC expression levels.Furthermore, the presence of high SPARC expression was an independent prognostic factor for both DFS (HR=1.67, 95%CI:1.04-2.69, P=0.034) and OS(HR=1.77, 95%CI:1.04-3.01, P=0.037) of triple-negative breast cancer patients, stratified on tumor grade, TNM stage, lymph node metastasis and vascular invasion, with adjustment for age, hormonal status, tumor size, adjuvant radiotherapy and adjuvant chemotherapy.
Conclusion: Our results suggest that the presence of higher SPARC expression could be an indicator of high aggressiveness and may be a strong prognostic factor for triple-negative breast cancer.
Citation Format: Zhu A, Yuan P, Du F, Ding X, Xu B. Impact of high SPARC expression of a primary tumor as a strong risk factor for disease recurrence and overall survival in patients with triple-negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-60.