bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-05-02: Overexpression of the chemokine receptor CCR2 in the breast epithelium is associated with progression of DCIS
Authors: Mafuvadze Benford , Fang Wei Bin , Cheng Nikki 
Published: May 2015

Abstract
Ductal carcinoma in situ (DCIS) is the most common type of non-invasive breast cancer diagnosed in women and an immediate precursor to invasive ductal carcinoma (IDC). It is largely unclear why some cases of DCIS progress to IDC, while others remain non-invasive. Current cyto- and histopathological approaches do not accurately predict disease progression, resulting in patients being under-treated or over-treated for DCIS. Our long-term goals are to identify key factors that lead to IDC that will enable the development of a molecular based approach to predict the risk of IDC, and a more tailored approach to treat DCIS. The CCL2/CCR2 chemokine pathway is best known for regulating macrophage recruitment to late stage breast tumors. In recent studies, we found that CCR2 and its binding ligand CCL2 were overexpressed in breast ductal carcinomas, correlating with tumor grade and poor patient prognosis. To further investigate the significance of CCR2 and CCL2, we performed flow cytometry analysis of breast epithelial cell lines, and found that increased CCR2 overexpression but not CCL2, was associated with invasive potential of the cell lines. CCL2 was found to be increased in stromal cells, particularly in cancer associated fibroblasts. Using a mammary intra-ductal injection model, we further examined for expression patterns of CCR2 and CCL2 in DCIS lesions derived from DCIS.com and Sum225 cells. Increased CCR2 was detected in DCIS.com lesions, which progressed to IDC within 10 weeks of injection, while CCR2 expression was found to be lowly expressed in non-invasive Sum225 lesions. CCL2 was detected in the stroma of both DCIS.com and Sum225 lesions. Overexpression of CCR2 in cultured non-invasive 67NR mammary carcinoma cells enhanced cell survival and increased wound closure. CCL2 treatment further enhanced cell survival and wound closure of CCR2 overexpressing 67NR cells. Knockdown of CCR2 in DCIS.com cells in 3D Matrigel: collagen cultures inhibited cellular invasion into the matrix. These studies indicate that CCR2 overexpression in ductal carcinoma cells, enhances intracellular signaling, and contributes to development of IDC. These data suggest that targeting the CCR2 pathway may be promising strategy for prevention or treatment of IDC.
Citation Format: Benford Mafuvadze, Wei Bin Fang, Nikki Cheng. Overexpression of the chemokine receptor CCR2 in the breast epithelium is associated with progression of DCIS [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-02.
Abstract P4-05-13: PTEN deletion is linked to adverse phenotype and poor prognosis in breast cancer
Authors: Burandt Eike , Kluth Martina , Kopperschmidt Valerie , Mittenzwei Anja , Lebeau Annette , Müller Volkmar , Witzel Isabell , Jänicke Fritz , Geist Stefan , Paluchowski Peter , Wilke Christian , Heilenkötter Uwe , Krech Rainer , von d Assen Albert , Simon Ronald , Lebok Patrick 
Published: May 2015

Abstract
Deletions of chromosome 10q23, including the PTEN (phosphatase and tensin homolog) locus, are known to occur in breast cancer, but systematic analyses of its clinical relevance are lacking. We thus analyzed a tissue microarray (TMA) with 2,197 breast cancers by fluorescence in-situ hybridization (FISH) using a PTEN-specific probe, and found deletions in 19% of no special type, 9% of lobular, 46% of medullary and 4% of tubular cancers. 98.7% of deletions were heterozygous and 1.3% were homozygous. PTEN deletion was significantly linked to advanced tumor stage (p=0.0054), high tumor grade (p&lt;0.0001), high tumor cell proliferation (Ki67 Labeling Index; p&lt;0.0001), and shortened overall survival (p=0.0090). PTEN deletions were inversely associated with features of luminal type breast cancers (ER/PR positivity, CCND1 amplification). PTEN deletions were strongly linked to amplification of genes involved in the PTEN/AKT pathway such as MYC (p=0.0430) and HER2 (p=0.0065). Remarkably the combined analysis of MYC, HER2, and PTEN aberrations suggested that aberrations of multiple PTEN/AKT pathway genes have a strong additive effect on breast cancer prognosis. Cancers with two or three of these aberrations behaved significantly worse than cancers with none or one of these changes (p&lt;0,0001). The particularly poor prognosis of patients with HER2 amplification and PTEN deletions challenges the concept of PTEN deletions interfering with trastuzumab therapy. In conclusion, PTEN deletion occurs in a relevant fraction of breast cancers, and is linked to aggressive tumors. Reduced PTEN function cooperates with MYC and HER2 activation in conferring aggressive phenotype to cancer cells.
Citation Format: Eike Burandt, Martina Kluth, Valerie Kopperschmidt, Anja Mittenzwei, Annette Lebeau, Volkmar Müller, Isabell Witzel, Fritz Jänicke, Stefan Geist, Peter Paluchowski, Christian Wilke, Uwe Heilenkötter, Rainer Krech, Albert von d Assen, Ronald Simon, Patrick Lebok. PTEN deletion is linked to adverse phenotype and poor prognosis in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-05-13.
Abstract P4-07-10: MiRNAs are important regulators of Pax-5 expression and function during breast cancer progression
Authors: Harquail Jason M , Robichaud Gilles A 
Published: May 2015

Abstract
Recent studies have enabled the identification of important factors regulating cancer progression, one of these being the Pax-5 gene. Pax-5, an essential developmental factor of B cells, is aberrantly expressed in various B cell cancer lesions and solid tumors such as breast carcinoma. Although Pax-5 downstream activity is relatively well characterized, the regulation of aberrant Pax-5 expression in a cancer specific context is poorly understood. To investigate the regulation of Pax-5 expression, we turned our attention to micro-RNAs (miRNAs). MiRNAs are highly conserved, small non-coding RNA molecules that regulate key biological processes. Extensive studies also show their deregulation in multiple cancer lesions. In this study, we aim to elucidate a causal link between differentially expressed miRNAs in cancer cells and their putative targeting of Pax-5-dependent cancer processes. With the help of biobank data and bioinformatics analyses, we observe that miRNAs 484 and 210 are aberrantly expressed in breast cancer cells and cross-reference with their predicted capacity to target the Pax-5 mRNA 3’ untranslated region (3’UTR). Using anti- or pre-miRNAs transfected into Pax-5 expressing breast cancer cell lines (MCF-7 and MB231), we demonstrate that miRNAs 484 and 210 are capable of regulating Pax-5 expression. In addition, miRNA-regulated Pax-5 expression resulted in a concomitant alteration in Pax-5-mediated phenotype and cancer processes. This is the first study demonstrating the regulation of Pax-5 expression and function by non-coding RNAs in cancer cells. We believe that the aberrant expression of Pax-5 in cancer cells is in part due to deregulated miRNA expression profiles. This study will bring insight in regards to cancer regulating processes associated with miRNA and Pax-5 deregulations and help us better understand aberrant Pax-5 expression levels within cancerous states. This study can therefore provide the eventual possibility of earlier, more efficient diagnostics as well as more targeted treatments for cancer patients.
Citation Format: Jason M Harquail, Gilles A Robichaud. MiRNAs are important regulators of Pax-5 expression and function during breast cancer progression [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-07-10.
Abstract P4-07-12: Re-introduction of tumor suppressor miR-34a harbors therapeutic efficacy in triple negative breast cancer
Authors: Adams Brian D , Pusztai Lajos , Rimm David L , Slack Frank J 
Published: May 2015

Abstract
Place Holder Abstract
Date Expected for Obtaining Final Information for Abstract: 9/14 - 10/14
Triple negative breast cancer accounts for a disproportionate share of the total breast cancer morbidity because of its aggressive behavior, increased incidence in younger women, and lack of effective targeted therapies. MicroRNAs are global regulators of survival and proliferation pathways important in cancer development and tumor maintenance. MicroRNAs function as tumor suppressors and oncogenes, and are highly dysregulated in cancer. Here, we identified miR-34a to be aberrantly lost in triple negative cancer cell lines when compared to both a luminal cancer subtype as well as normal breast cells. Re-introduction of miR-34a in triple negative cancer lines results in inhibition of cell proliferation, reactivation of senescence, and enhances sensitivity to apoptotic-inducing agents. Furthermore, intratumoral delivery of miR-34a into subcutaneously implanted tumors in nude mice delays tumor growth as compared to a scrambled control. In conclusion re-introduction of miR-34a in triple negative breast cancer promotes anti-tumorigenic phenotypes both in vitro and in vivo, and could therefore be used as a therapeutic agent to treat the disease.
Citation Format: Brian D Adams, Lajos Pusztai, David L Rimm, Frank J Slack. Re-introduction of tumor suppressor miR-34a harbors therapeutic efficacy in triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-07-12.
Abstract P4-11-09: Comparison of immunohistochemical residual risk panels to predict risk in early breast cancers treated with endocrine therapy
Authors: Stephen Jacqueline , Murray Gordon , Cameron David , Thomas Jeremy , Kunkler Ian , Jack Wilma , Kerr Gill , Piper Tammy , Brookes Cassandra , Rea Daniel , van de Velde Cornelis , Hasenburg Annette , Markopoulos Christos , Dirix Luc , Seynaeve Caroline , Bartlett John 
Published: May 2015

Abstract
Background: We compare two residual risk models combining immunohistochemical (IHC) biomarkers, IHC4 and Mammostrat, in the Edinburgh Breast Conservation Series (BCS) and in the Tamoxifen versus Exemestane Adjuvant Multinational (TEAM) trial.
Materials and Methods: The primary cohorts comprised 831 and 2,513 estrogen receptor (ER)-positive patients who did not receive adjuvant chemotherapy from the Edinburgh BCS and TEAM cohorts respectively. We evaluated prognostic scores for distant recurrence-free survival (DRFS).
Results: Low scores for both IHC4 and Mammostrat are associated with better DRFS. In multivariate Cox regression analyses the addition of both scores to clinical factors provided independent information on residual risk (p&lt;0.05). In the larger TEAM cohort, IHC4 was the stronger predictor of DRFS but additional information was gained from including the Mammostrat score for all ER-positive patients (p&lt;0.001).
Conclusion: The results showed that the scores have different capabilities in predicting DRFS depending on the study and subgroup of patients. However, significant benefit in estimating residual recurrence risk after treatment was observed from a combined use of both marker panels. This provides support for investigating their combined use for risk stratification of ER-positive early breast cancer patients.
Citation Format: Jacqueline Stephen, Gordon Murray, David Cameron, Jeremy Thomas, Ian Kunkler, Wilma Jack, Gill Kerr, Tammy Piper, Cassandra Brookes, Daniel Rea, Cornelis van de Velde, Annette Hasenburg, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, John Bartlett. Comparison of immunohistochemical residual risk panels to predict risk in early breast cancers treated with endocrine therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-09.
Abstract P4-11-10: Time dependence of biomarkers: Non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer
Authors: Stephen Jacqueline , Murray Gordon , Cameron David , Thomas Jeremy , Kunkler Ian , Jack Wilma , Kerr Gill , Piper Tammy , Brookes Cassandra , Rea Daniel , van de Velde Cornelis , Hasenburg Annette , Markopoulos Christos , Dirix Luc , Seynaeve Caroline , Bartlett John 
Published: May 2015

Abstract
Background: We investigate the impact of follow-up duration to determine whether two immunohistochemical prognostic panels, IHC 4 and Mammostrat, provide information on the risk of early or late distant recurrence using the Edinburgh Breast Conservation Series and the Tamoxifen versus Exemestane Adjuvant Multinational (TEAM) trial.
Methods: The multivariable fractional polynomial time (MFPT) algorithm was used to determine which variables had possible non-proportional effects. The performance of the scores was assessed at various lengths of follow-up and Cox regression modelling performed over the intervals 0-5 years and &gt; 5 years.
Results: We observed a strong time-dependence of both the IHC4 and Mammostrat scores with their effects decreasing over time. In the first five years of follow-up only, the addition of both scores to clinical factors provided statistically significant information (p&lt;0.05) with increases in R2 between 5 and 6% and increases in D-statistic between 0.16 and 0.21.
Conclusion: Our analyses confirm that the IHC4 and Mammostrat scores are strong prognostic factors for time to distant recurrence but this is restricted to the first 5 years after diagnosis. This provides evidence for their combined use to predict early recurrence events in order to select those patients who may/will have benefit from adjuvant chemotherapy.
Citation Format: Jacqueline Stephen, Gordon Murray, David Cameron, Jeremy Thomas, Ian Kunkler, Wilma Jack, Gill Kerr, Tammy Piper, Cassandra Brookes, Daniel Rea, Cornelis van de Velde, Annette Hasenburg, Christos Markopoulos, Luc Dirix, Caroline Seynaeve, John Bartlett. Time dependence of biomarkers: Non-proportional effects of immunohistochemical panels predicting relapse risk in early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-10.
Abstract P4-13-02: BRCA1/2 founder mutations among high-risk HBOC patients from Northeast of Brazil
Authors: Nascimento Ivana L , Felix Gabriela ES , Sandes Camila A , Machado-Lopes Taisa B , Bomfim Thais F , Meyer Roberto , Romeo Maura , Toralles Betania , Sandes Kiyoko A 
Published: May 2015

Abstract
Background: Genetic susceptibility to Hereditary Breast and Ovarian Cancer (HBOC) syndrome could be test by the screening of BRCA1 and BRCA2 genes. Thus, knowing that each population has its degree of heterogeneity and the Brazilian population is one of the most heterogeneous of the world, we aimed to verify the frequency of BRCA1/2 founder mutations in high-risk HBOC patients from Bahia, the biggest State of the Northeast of Brazil.
Methods: It was analyzed the DNA of 98 unrelated high-risk HBOC patients, considering the criteria of NCCN v.1.2010. These patients were tested for the next founder mutations: BRCA1 c.211A&gt;G (Galician), BRCA1 943ins10 (African), BRCA1 3450del4 (Hispanic) and BRCA2 c.5946_5946delT (Portuguese) by sequencing or PCR/RFLP. All positive results were confirmed by two sequencing reactions. The genetic ancestry was analyzed with a panel of 10 ancestry informative markers (AIMs). The clinical and epidemiological data were collected during the genetic counseling and were analyzed in Epi InfoTM 7, while the frequency of the AIMs was analyzed in GENEPOP, and in ADMIX95 the genetic admixture was estimated.
Results: All patients had personal and/or familial history of breast and/or ovarian cancer. Most of the patients self-reported as mulatto (61.23%), followed by black (21.43%), white (10.20%) and others (7.14%). The African, Amerindian and European ancestry contribution estimated were 35.33%, 11.31% and 53.35% respectively (R2 = 0.998). Two mutations were detected the BRCA1 3450del4 in five patients (4.90%) and the BRCA1 c.211A&gt;G in two patients (2.04%). All patients with these mutations were from State of Bahia and self-reported as mulatto or white. Any carrier declared as Spanish descendant.
Conclusion: Although the Portuguese settled Brazil, here it was observed that this population seems to have high Spanish ancestry contribution, due to the high frequency of the BRCA1 3450del4 and c.211A&gt;G (6.94%). It is also interestingly the absence of BRCA1 943ins10, because the State of Bahia has the higher rate of African-descendants in Brazil and most of the patients exhibited these physical traits (mulatto and black, 82.65%). Thus, high-risk patients from that region of Brazil could be screening first for the BRCA1 3450del4 and BRCA1 c.211A&gt;G, where it has a founder effect.
Citation Format: Ivana L Nascimento, Gabriela ES Felix, Camila A Sandes, Taisa B Machado-Lopes, Thais F Bomfim, Roberto Meyer, Maura Romeo, Betania Toralles, Kiyoko A Sandes. BRCA1/2 founder mutations among high-risk HBOC patients from Northeast of Brazil [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-13-02.
Abstract P4-14-04: United States breast cancer mortality trends in young women according to race
Authors: Ademuyiwa Foluso O , Gao Feng , Hao Lin , Morgensztern Daniel , Aft Rebecca L , Ma Cynthia X 
Published: May 2015

Abstract
Purpose
Studies have shown that there is a negative prognostic impact of young age at diagnosis on clinical outcome in women with breast cancer (BC). We sought to determine if there is a differential effect of race in this high-risk population of women and examined mortality trends according to race and diagnosis age.
Methods
Using the Surveillance, Epidemiology, and End Results (SEER) program 1990-2009, women diagnosed with invasive BC under the age 50 were identified. Clinicopathologic characteristics, overall survival, and BC specific survival rates were compared between racial groups. After adjustments for stage, ER, PR, histology, age, diagnosis year, tumor size, nodal status, and grade, multivariate logistic regression analyses determined the risk-adjusted likelihood of survival for whites and blacks. Annual hazard rates (HR) of BC deaths after diagnosis according to race and calendar period, and adjusted relative hazards of death for white and black women stratified by age at diagnosis were computed.
Results
Overall, 162,976 women were identified, including 126,573 whites (77.7%), 20,405 blacks (12.5%), and 15,998 of other races (9.8%). At a median follow-up of 85 months, five year disease specific survival rates were 90.1% for whites, and 79.3% for blacks. During the study period, the annual HR for death in whites decreased by 26% at 5 years after diagnosis, in contrast to the rates in blacks women decreasing by only 19%. With 1990 as referent, adjusted relative hazards for death in 2005 for white and black women &lt;40 years were 0.55 (95% CI 0.46-0.66) and 0.68 (95% CI 0.49-0.93) respectively. In whites and blacks ≥40, 2005 hazards were 0.53 (95% CI 0.47-0.60) and 0.78 (95% CI 0.61-0.99).
Conclusion
Among young women diagnosed with BC, blacks have a worse outcome than whites. Mortality declines in both racial groups have been observed over time, although more rapid gains have occurred in whites. Emphasis should be placed on improving outcomes for young BC patients.
Citation Format: Foluso O Ademuyiwa, Feng Gao, Lin Hao, Daniel Morgensztern, Rebecca L Aft, Cynthia X Ma. United States breast cancer mortality trends in young women according to race [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-14-04.
Abstract P4-15-06: Correlation between ERBB2 mRNA levels, HER2-dependence and susceptibility to trastuzumab in human breast cancer
Authors: Tagliabue Elda , Regondi Viola , De Cecco Loris , Pupa Serenella M , Campiglio Manuela , Carcangiu Maria Luisa , Ménard Sylvie , Triulzi Tiziana 
Published: May 2015

Abstract
While results thus far demonstrate the clinical benefit of trastuzumab in breast cancer, some patients do not respond to this reagent. Identifying a robust clinical or molecular predictor of adjuvant trastuzumab benefit has proven challenging and even the most obvious candidate biomarker for a predictor of trastuzumab benefit, HER2 expression as assessed by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH), has proven to be surprisingly ambiguous in realizing benefit from the antibody. Results of a recent study that profiled expression of select genes in archived formalin-fixed, paraffin-embedded (FFPE) tumor blocks from a randomized study of breast cancer patients treated with adjuvant trastuzumab support a relationship between ERBB2/ESR1 mRNA levels and trastuzumab sensitivity. Based on that observation, we conducted whole-genome profiling by DASL technology of archival FFPE tumor blocks from 53 HercepTest 3+/2+ FISH-positive patients treated with adjuvant trastuzumab in our Institute; 308 genes were significantly associated with relapse-free survival by Cox proportional hazard model (α&lt;0.005; permutation test p&lt;0.01). We then developed a relapse risk 41-gene classifier (TRAR) able to discriminate cases mainly according to ERBB2 and ESR1 mRNA expression levels and to predict tumor relapse in both trastuzumab adjuvant and neoadjuvant settings. No correlation was found between ERBB2 mRNA and HER2 protein expression (the latter assessed by IHC on FFPE tumor sections using serial dilutions of anti-HER2 antibody), nor did HER2 protein expression correlate with relapse risk in these tumors. Analysis of HER2-amplified breast carcinoma cell lines revealed higher levels of ERBB2 mRNA in oncogene-addicted than in non-addicted cells in correlation with HER2 activation assed by Western blot but not with total HER2 protein amount. Moreover, ERBB2 mRNA expression levels in HER2-amplified breast carcinoma cells correlated with trastuzumab-mediated cellular cytotoxicity (ADCC) in vitro (r=0.96, p=0.038), whereas no correlation was found between ADCC and membrane-associated HER2.
Together, our findings strongly suggest that ERBB2 mRNA, but not protein levels, mirror HER2 activity and thus oncogene addiction of tumor cells and susceptibility to trastuzumab in amplified HER2-positive tumors.
Supported by AIRC.
Citation Format: Elda Tagliabue, Viola Regondi, Loris De Cecco, Serenella M Pupa, Manuela Campiglio, Maria Luisa Carcangiu, Sylvie Ménard, Tiziana Triulzi. Correlation between ERBB2 mRNA levels, HER2-dependence and susceptibility to trastuzumab in human breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-06.