bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-10-01: MicroRNAs −181 and −135a modulate tumour infiltrating immune cell programs in distinct molecular breast cancer subtypes
Authors: Paladini L , Truglia M , Arcangeli A , De Mattos Aruda L , Bianchini G , Iwamoto T , Bottai G , Pusztai L , Calin GA , Di Leo A , Santarpia L 
Published: August 2014

Abstract
Background and Aims: MicroRNAs (miRNAs) are short non-coding RNA whose expression levels have diagnostic and prognostic implications in cancer. However, the relevance of aberrantly expressed miRNAs to breast tumour-immune response has not been established. We aimed to assess the association between deregulated miRNAs and tumour immune response in breast molecular cancer subtypes.
Methods: One hundred and seventy ductal infiltrating breast carcinomas (BC) (ER+/HER2− n=85, HER2+ n=40, ER−/HER2− n=45) were evaluated for the presence of cellular immune components by IHC assay. CD3, CD20 were used as markers for T lymphocytes infiltration (TIL), and B lymphocytes infiltration (BIL), respectively, whereas CD68 for the presence of tumour-associated macrophage (TAM). Total RNA (including miRNA) was extracted from all tumours and 32 highly specific miRNAs and 276 immune genes were evaluated by array and qRT-PCR assays. We derived an integrated immune miRNA-regulatory gene profile to tease out relationships of these genes as potential targets of specific miRNAs. In vitro experiments on BC cell lines were performed to confirm potential links between deregulated miRNAs and immune genes.
Results: Lymphocytes infiltration (LI) was most common in HER2+ and ER−/HER2− BC samples (P &lt; .004 and &lt; .001) although B and T cells components were differently distributed in these 2 BC groups. TAM was a frequent event in ER−/HER2− BC subtype (P &lt; .005). By gene and integration analyses we identified important miRNA immune-modulated target genes associated with prognostic factors and with molecular BC subtypes. We focused our studies on miR-181 and miR-135a that were significantly associated with ER−/HER2− (P &lt; .001) and HER2+ BC (P &lt; .002), respectively. BCs with abnormal expression of miR-181 and miR-135a showed an important association with distinct TIL and TAM components and specific immune genes. Importantly, preclinical data on BC cell lines demonstrated that miR-181 and miR-135a were able to regulate important cell immune-modulators such as SEMA3B and STAT6 signalling pathways, respectively. These 2 cellular pathways in turn were capable to regulate specific cascades of immune gene networks.
Conclusion: We identified specific miRNAs associated with immune cellular components and immune-related tumour response in the 3 main molecular BC subtypes (ER+/HER2−, HER2+ and ER−/HER2). Aberrant expression of miR-181 and miR-135a can contribute to BC tumour immune response programs by regulating important gene targets such as SEMA3B and STAT6 signalling pathways in ER−/HER2− and HER2+ tumours, respectively. Modulation of miRNAs activating tumour immune response programs may have important implications for novel therapeutic strategies in BC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-01.
Abstract P5-10-10: The miR-34a is down-regulated in breast cancer and breast stem cells and a potential to eradicating breast cancer via a systemic delivery of a VISA –miR-34a nanoparticle system
Authors: Xie X , Li L , Xie X , Wei W , Kong Y , Wu M , Yang L , Gao J , Xiao X , Tang J , Xie Z , Wang X , Liu P , Li X , Guo J 
Published: August 2014

Abstract
Breast cancer is the most common disease in women around the world and the current treatment strategies are not potent enough for the patients, especially those who are the triple-negative type of molecular classifications. Therefore, novel and more effective treatments are pressingly needed. Of the current methods, target therapy, which not only retains cancer-specific expression but also limits toxicity, is a new strategy for treatment of cancers. In this study, it was to investigate miR-34a expression in breast caner specimen and its relationship with patient's clinical status, and develop targeted miR-34a delivery system as a potential method for breast cancer therapy. miR-34a expression was investigated by qRT-PCR and related to clinicopathologic significance and found to be down-regulated in breast cancer as compared with normal adjacent tissues and involved in breast cancer stem cell through down-regulation of CD44, ZEB1, and Bmi1. We designed targeted miR-34a expression using T-VISA system (hTERT promoter driven VP16-Gal4-WPRE Integrated Systemic Amplifier) liposomed-based nanoparticles and evaluated the antitumor effect in breast cancer cells in vitro and in orthotopic animal model as well as its systemic toxicity. The T-VISA-miR-34a system robust targeted to breast cancer cells and breast cancer stem cells and prolonged duration expression of miR-34a. Furthermore, a systemic delivery of a VISA –miR-34a nanoparticle system targeted efficiently expression of miR-34a to tumors and could significantly inhibit tumor growth and prolong mouse survival in multiple living imaging xenograft and syngeneic models of orthotopic breast cancer and without toxicity in intact mice. Our study demonstrated that miR-34a expression was down-regulated in breast cancer and breast cancer stem cells through down-regulation of CD44, ZEB1, and Bmi1. The T-VISA-miR-34a nanoparticle system showed robust antitumor effects in breast cancer and could be a potential therapeutic approach to eradicating breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-10.
Abstract P5-10-15: Genetic variants located in beta2 adrenergic receptor gene (ADRB2) and miRNA let-7 binding site alter breast cancer susceptibility: a case control analysis
Authors: Du Y , Lu J 
Published: August 2014

Abstract
Previous studies have shown that a potential association may exist between risk of breast cancer and polymorphisms in the beta-adrenergic receptor gene. ADRB2 is a target for miRNA let-7 and it is reported that low let-7 expression probably increases risk of breast cancer. In this study, we investigated the relationship between genetic variants located in alpha2 and beta2 adrenergic receptor genes and miRNA let-7 binding sites with breast cancer risk in benign mammary disease and sporadic breast cancer. We assessed frequency distributions of these variants in 741 patients with histologically confirmed breast cancer and 315 controls with benign mammary disease. We initially demonstrated that rs1042713, located in ADRB2 and rs11292, located in miRNA let-7 binding site were associated with susceptibility to breast cancer. A significant association was observed between GG, AG+GG genotype compared to AA genotype of SNP rs1042713 and a decreased breast cancer risk (adjusted OR = 0.79, 95%CI: 0.64–0.97, p = 0.025; adjusted OR = 0.72, 95%CI: 0.54–0.96, p = 0.028). We also found a significant association between TC, TC+CC genotype compared to TT genotype of SNP rs11292 and an increased breast cancer risk (adjusted OR = 1.44, 95%CI: 1.01–2.06, p = 0.044; adjusted OR = 1.43, 95%CI: 1.01–2.02, p = 0.044). The allele of G of SNP rs1042713 was associated with a decreased risk of breast cancer (OR = 0.79, 95%CI: 0.66–0.96, p = 0.018). Taken together, our study demonstrated that genetic variants located in ADRB2 and miRNA let-7 binding site could alter breast cancer risk.
Keywords: ADRB2 gene, miRNA let-7, polymorphism, breast cancer
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-15.
Abstract P5-10-16: miRNAs as novel therapeutic adjuvants for the prognosis and treatment of triple negative breast cancers
Authors: Zoghi B , Chang Y-F , Subbarayalu P , Plyler JR , Rao M 
Published: August 2014

Abstract
Approximately 15–20% of all breast cancers account for triple negative breast cancers (TNBCs) that exhibit an aggressive, distinct metastatic pattern and poor prognosis resulting in a disproportionate number of breast cancer deaths. More than 50% of patients with TNBC develop chemoresistance and do not respond to chemotherapeutic drugs, leading to early relapse and shorter survival. Understanding the mechanisms underlying such resistance is therefore crucial for the development of new, efficacious cancer drugs. In spite of extensive inquiry in this field, little is known about the key molecules/signaling pathways that regulate this phenomenon. Recently, we have discovered that small non-coding RNAs-miRNAs play critical roles in mediating drug sensitivity/resistance in TNBCs. We have identified miRNAs that are differentially expressed between chemo-resistant and sensitive breast cancer cells. In particular, through high-throughput miRNA inhibitor library screens, we have identified miRNA inhibitors that sensitize resistant TNBC cells to paclitaxel, a drug commonly used to treat triple negative breast cancers. Interestingly, our studies revealed that specific miRNAs including miR-185 (patent pending) that sensitize resistant TNBCs to paclitaxel are expressed at significantly lower levels in relapsed metastatic TNBC patient sera compared to sera from their healthy siblings. Furthermore, using liposome- or biocompatible PLGA nanoparticle-based approaches, we show that systemic delivery of one of the sensitizer miRNAs suppresses breast cancer lung metastasis without any hepatotoxicity in preclinical mouse tumor models. Importantly, we show that one of the mechanisms by which sensitizer miRNAs regulate paclitaxel sensitivity is by targeting Stathmin, a microtubule destabilizer protein that can bind to tubulin dimers and stimulate microtubule destabilization. These findings suggest that tumor-specific miRNAs render selective cell cytotoxicity in a drug-specific manner, that these miRNAs may serve as detection markers for identifying patients who might benefit most from specific drug treatment, and that these miRNAs may represent novel therapeutic tools for the treatment of the TNBCs. Since miRNAs are endogenously expressed and can be easily manipulated using synthetic oligoribonucleotides, we believe that they represent more attractive targets than the single gene or gene product targeted by conventional cancer treatments that are typically prone to drug resistance. Since paclitaxel is used for the treatment of many cancers, the long-term implications of this study are likely not limited to breast cancer alone but may apply to other tumor types.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-16.
Abstract P5-12-03: Developing the ePromotora: Increasing Promotora's Access to Breast Cancer Electronic Resources
Authors: Lopez AM , Ryan J , Valencia A , El-Khayat Y , Nunez A 
Published: August 2014

Abstract
Background: Disparities in breast cancer screening and survival have been attributed to multiple factors including limited access to breast health education. Innovative information technologies facilitate health education; however, access to information technology is not uniform. The resultant systematic gap in health knowledge has led to a new health disparity where higher socioeconomic individuals acquire health information electronically more easily than the disadvantaged. Promotoras or Community Health Workers (CHWs) facilitate access to culturally appropriate cancer health information, screening and care. Hypothesis: An electronic asynchronous breast cancer educational intervention developed by the Arizona Telemedicine Program and the Arizona Health Sciences Library will improve CHW computer literacy and will enhance health education communication.
Specific Aims: to develop, implement and assess a 6-session e-promotora training curriculum with a focus on breast health.
Methods: The first step in developing a training curriculum was a needs assessment and a computer literacy assessment. This assessment served as the foundation for the computer literacy curriculum which focused on breast health content. The educational intervention was delivered as a combination of on-line, webinar, and face-to-face seminars. To meet the needs of the participants all sessions were delivered bilingually, Spanish and English. Program evaluation included pre and post knowledge assessments, session assignments, program satisfaction and 6-month follow up focus groups or structured interviews to evaluate the utility, implementation and dissemination of knowledge gained.
Results: 26 CHWs have completed the training. All participants identified as Latinas, average age – 51 years of age and educational attainment – 58% (15/26) reported high school or less. Pre and post assessment data reveal high program satisfaction scores, increased participant knowledge and confidence in knowledge, consistent and ongoing use of information learned and computer skills gained and effective dissemination of health information gained.
Conclusions: The e-promotora training curriculum effectively improves CHW computer literacy, facilitates dissemination of electronic health information and helps address the disparities in electronic health information.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-12-03.
Abstract P5-14-05: Compliance with radiation therapy in breast cancer patients in Southeastern Kentucky
Authors: Elsoueidi R , Adane E , Dignan M 
Published: August 2014

Abstract
Background: Nearly a quarter of Americans live in rural areas, which consistently report higher cancer mortality rates than urban and suburban areas. The worse outcome for cancer patients in these areas has been attributed in part to compliance with treatment recommendations. Southeastern Kentucky is a rural area with a low income population and barriers such as distance and lack of public transportation to access health care and compliance with treatment is a major concern.
Methods: Data on patients with breast cancer treated with radiation therapy at Appalachian Regional Healthcare cancer center which serves the area of Southeastern Kentucky were collected. Age, economic status (measured by availability of medical insurance), distance of patient's residence from the hospital, were evaluated as potential predictors of compliance with recommendations to obtain radiation therapy. Data were analyzed with Fisher's exact test.
Results: A total of 80 patients with breast cancer received adjuvant radiation treatment from 2008 to 2011. Of these 80 patients, 24 (30%) had Medicaid, 31 (39%) had Medicare, and 25 (31%) had commercial health insurance. Only two (2.5%) patients did not complete treatment due to transportation. An additional 10 patients (13%) had treatment interruption due to weather, transportation or other financial reasons. In patients who completed treatment, a total of 2640 days of treatment were provided. A total of 55 (2.1%) days of treatment were missed. Of the 10 patients who had interruption, 5 of them had Medicaid and the number of missed days by the Medicaid patients was (37/55), which is 67% of the total days missed. No statistically significant difference was detected in the number of patients missing treatment between Medicaid and other insurance types (p = 0.16). None of the factors evaluated predicted patient compliance, although a trend toward lower compliance was noted in patients who had Medicaid.
Conclusion: Despite being a rural area with multiple barriers to access healthcare, the rate of full compliance (defined as completion of the entire course of radiation therapy) with adjuvant radiation therapy in breast cancer patients in Southeastern Kentucky was 97.5%, which is similar to the rates in clinical trials that generally exceed 90%. A trend toward lower compliance was noted in patients who had Medicaid although it was not statistically significant.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-14-05.
Abstract P5-15-04: CTX and CTX-related direct medication costs saved by testing biomarkers uPA and PAI-1 in primary breast cancer: Results of a prospective multi-center study at Certified Breast Centers in Germany
Authors: Jacobs VR , Augustin D , Wischnik A , Kiechle M , Hoess C , Steinkohl O , Rack B , Kapitza T , Krase P 
Published: August 2014

Abstract
Background: Biomarkers uPA and PAI-1 are guideline recommended by ASCO, USA, and AGO, Germany, to be used in primary breast cancer to avoid unnecessary CTX in medium risk recurrence patients [G2, N−, HR+, HER2neu−, &gt;35 years]. This study was performed to verify in normal clinical settings how many CTX cycles and how much CTX-related direct medication costs can be avoided by uPA/PAI-1 testing.
Methods: Prospective, non-interventional, multi-center study over two years among six Certified Breast Centers in Germany to analyze application of uPA/PAI-1 and consecutive decision making in the clinical setting for AOK Bayern-insured patients. CTX regimen and cycles avoided were identified for each case and direct costs for CTX and CTX-related medication costs for concomitant medication calculated for each patient individually according to body weight and body surface as well as potential FN prophylaxis according to physicians' decision. All medication costs were taken from the pharmaceutical price list for Germany Rote Liste of 2012. EURO [€] to US Dollar conversion rate as of June 12 2012: € 1.00 = US$ 1.25.
Results: In n=93 breast cancers n=35 CTX (37.6%; FEC n=25, FEC+DOC n=8 and TC n=2) were avoided according to uPA/PAI-1 test result. Consecutively 210 CTX cycles or 12.1 years of CTX application were saved improving patients' quality of life. uPA/PAI-1 testing saved direct medication costs for avoided CTX of US$ 221.816, CTX-related concomitant medication of US$ 34.353 and G-CSF prophylaxis of US$ 25.749, overall US$ 281.918. At process costs for a single uPA/PAI-1 test calculated at US$ 359, uPA/PAI-1 testing resulted in additional costs of US$ 33.387 for all breast cancer cases. Overall, testing of uPA/PAI-1 has been proven to be cost-effective regarding direct medication costs alone at a return-on-investment ratio of 8.4:1. Indirect cost savings further increase this ROI.
Conclusions: Innovative and individual cancer diagnostics like biomarkers uPA/PAI-1 can decrease need of CTX and increase patients' quality of life and thereby reduce costs for health care systems. Since application of this test is inadequate at present time measures are suggested to fully implement such cost-effective diagnostics.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-04.
Abstract P5-15-06: Societal economics of the 21-gene Recurrence Score® in estrogen-receptor-positive early-stage breast cancer in Japan
Authors: Yamauchi H , Nakagawa C , Yamashige S , Takei H , Yagata H , Yoshida A , Hayashi N , Hornberger J , Yu T , Chien R , Chao C , Yoshizawa C , Nakamura S 
Published: August 2014

Abstract
Background: Breast cancer incidence and breast-cancer mortality have been increasing in Japan. In estrogen-receptor-positive breast cancer, adding chemotherapy as adjuvant treatment is not definitive benefit for all women. Primary data on the clinical validity and decision impact of the 21-gene Recurrence Score for guiding the use of adjuvant chemotherapy has been studied among a Japanese population.
Objective: The cost-effectiveness of the clinically validated 21-gene Recurrence Score for estrogen-receptor-positive, lymph-node-negative, early-stage breast cancer (ESBC) was assessed from a Japanese societal perspective.
Method: The proportion of patients with low, intermediate, and high risk of recurrence by the 21-gene Recurrence Score and the influence of the Recurrence Score on use of adjuvant chemotherapy were obtained in a study of 104 patients. A Markov model was used to track time until distant recurrence and time from distant recurrence to death. Effect of adjuvant chemotherapy based on 21-gene Recurrence Score was based on published clinical validation studies. Direct and indirect medical costs were obtained from the referral center. Utilities associated with progression and adverse events associated with chemotherapy were extracted from the literature. Sensitivity analyses were performed to assess the key drivers of cost-effectiveness and the robustness of the findings to variations in the input estimates.
Results: Forty-eight percent of patients were identified by the 21-gene Recurrence Score as low-risk, 36% as intermediate-risk, and 16% as high-risk. In treatment decision by using the 21-gene Recurrence Score, chemotherapy use overall decreased by 19%, resulting in an average increase of 0.235 QALYs. Testing with the 21-gene Recurrence Score cost ¥350,000 per patient with ¥153,490 lower acute costs because fewer women were treated with adjuvant chemotherapy. Eighteen percent more women who were identified as high risk were recommended adjuvant chemotherapy, which results in longer progression-free survival. On average across all risk groups, cost of monitoring until recurrence per patient increased by ¥3,572 and costs associated with recurrence declined by ¥43,687. Use of the 21-gene Recurrence Score resulted in a net cost of ¥665,455 ($8,386) per QALY gained.
Conclusions: The change in decisions resulting from use of the 21-gene Recurrence Score in women with estrogen-receptor-positive, lymph-node-negative, ESBC is projected to be societally cost-effective in Japan.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-06.
Abstract P5-16-01: Survival advantage in patients with metastatic breast cancer receiving endocrine therapy plus Sialyl Tn-KLH vaccine: post hoc analysis of a large randomized trial
Authors: Ibrahim NK , Murray JL , Zhou D , Mittendorf EA , Sample D , Tautchin M , Miles D 
Published: August 2014

Abstract
Background: A multicenter, double blinded, randomized phase III trial of the therapeutic cancer vaccine STn-KLH was completed in an international cohort of 1,028 women with metastatic breast cancer who had either no evidence of disease or nonprogressive disease following first-line chemotherapy. This trial is registered with ClinicalTrials.gov (No. NCT00003638). The outcomes showed that STn-KLH was safe and relatively well tolerated but had neither a positive nor negative effect on time to progression (TTP) or overall survival (OS) duration in the intent-to-treat population when compared with KLH control alone. The purpose of this post hoc analysis is to explore the potential benefit of combining an antiestrogen with MUC1 vaccines in metastatic breast cancer patients.
Methods: The data were further explored to determine if a retrospective, reassigned endocrine subset patient stratification produces subgroups that may have experienced benefit in TTP or survival compared with the phase III trial ITT analysis.
Results: Women treated with concomitant endocrine therapy, a pre stratified subset comprising approximately one third of the original study population, achieved a clinical benefit both in terms of TTP and survival compared with women who did not receive endocrine therapy. Moreover, women in the endocrine-treatment subset who mounted a median or greater antibody response (titer &gt;1:320 toward bovine submaxillary mucin) to the STn-KLH vaccine experienced significantly longer median survival than their trial counterparts who mounted a below-median antibody response.
Conclusion: Unlike maintenance chemotherapy, with its associated cumulative toxicity, the combination of endocrine and STn-KLH therapy may offer clinical benefit with few adverse effects for women with metastatic breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-16-01.
Abstract P5-17-02: Molecular response in breast cancer tumors treated with neoadjuvant chemotherapy with and without bevacizumab: Results from NeoAva - a randomized phase II study.
Authors: Engebraaten Olav , Silwal-Pandit Laxmi , Fleischer Thomas , Borgen Elin , Garred Øystein , Fangberget Anne , Holmen Marit M , Schlichting Ellen , Skjerven Helle , Lundgren Steinar , Gribbestad Ingrid S , Krohn Marit , Edvardsen Hege , Kristensen Vessela N , Mills Gordon , Wist Erik , Børresen-Dale Anne-Lise 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-02.