bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-05-11: Proteomic identification and in-silico verification of subtype-specific signatures in breast cancer.
Authors: Pavlou MP , Dimitromanolakis A , Diamandis EP 
Published: August 2014

Abstract
Breast cancer is a highly heterogeneous disease with different subtypes presenting distinct clinical characteristics. During the last decade has been shown that molecular classification of breast cancer holds the promise for the development of novel prognostic tools and the identification of novel treatment targets. However, proteins are the main mediators of biological processes and the molecular targets of the majority of drugs. Moreover, the proteome integrates the cellular genetic information and environmental influences. Hence coupling proteomic and transcriptomic studies may augment the development of targeted therapies and the identification of disease-relevant proteins networks.
Here, we report an extensive mass spectrometry-based (MS) secretome analysis of eight breast cancer cell lines representing, the three main breast cancer subtypes (luminal, basal and HER2-neu amplified) in search of subtype-specific proteomic signatures. Following a bottom-up proteomic approach coupled to tandem mass spectrometry the conditioned media of 8 breast cancer cell lines were analyzed. More than 5,200 non-redundant proteins were identified in the conditioned media of the 8 cell lines with a false positive rate less than 1%. The mass spectrometry-based identification of 5 proteins was successfully verified by ELISA.
For the generation of subtype-specific proteomic signatures, proteins common to all cell lines of the same subtype but not present in the other two subtypes were identified. Twenty-three, four and four proteins were found uniquely in basal, HER2-neu amplified and luminal breast cancer cells. Notably, ERBB2 was one of the proteins uniquely identified in the HER2-neu amplified subtype verifying the validity of our approach.
Given that most of these proteins have no quantitative methods available at present, we opted to preliminarily examine the relationship of these candidates with breast cancer subtypes by using an in silico approach, based on transcriptomic data. We performed an in silico mRNA expression analysis using publicly available data from four independent experiments containing a total of 1039 patients with primary breast cancer. The expression profiles of 15 of 31 proteins investigated showed significant correlation with estrogen receptor expression and power to distinguish subtypes. The development of multiplex quantitative mass spectrometry-based assays for the quantification of the proteomic signatures in relevant biological specimens along with immunohistochemical studies for two of the 31 candidates are currently ongoing.
The significance of these subtype-specific proteins in breast cancer prognosis and disease progression warrants further investigation.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-11.
Abstract P2-05-14: Clinical significance of Lysil oxidase-like 2 (LOXL 2) in breast cancer
Authors: Ahn SG , Lee HM , Hwang SH , Lee SA , Jeong J , Lee H-E 
Published: August 2014

Abstract
Introduction: Several preclinical studies provided relevant evidences that lysine oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. To investigate the clinical significance of LOXL2, we performed survival analysis with LOXL-2 in breast cancer patients.
Method: A cohort treated at Gangnam Severance hospital, Seoul, Korea between January 1996 and December 2004 was studied. The immunohistochemical analyses with LOXL-2 antibody were performed in the 309 patients. The patients was stratified into two groups based on the expression level of LOXL-2. Kaplan-Meier and Cox's methods were used to define prognostic factors associated with breast cancer survival.
Results: LOXL-2 positive group was 50 patients (16.2%) and 259 patients (83.8%) are LOXL-2 negative group. The proportion of estrogen receptor-negative patients was significantly higher in LOXL-2 positive group (54.0 vs. 37.0 %, P = 0.040). The Kaplan-Meier overall survival estimate at 5 year for the breast cancer patients with negative LOXL-2 was higher than that for the patients with positive LOXL-2 (88.0 vs. 71.8 %, P = 0.008). In the multivariate analysis for overall survival, lymph node metastasis (Hazard Ratio (HR) 0.32, 95% confidence interval (CI) 0.17–0.61) and positive LOXL-2 (HR 0.53, 95% CI 0.29–0.97) were significantly associated. In the multivariate analysis for distant metastasis-free survival, age younger than 35 years (HR 0.52, 95% CI 0.30–0.91), lymph node metastasis (HR 0.29, 95% CI 0.16–0.54), high histologic grade (HR 0.54, 95% CI 0.32–0.89) and positive LOXL-2 (HR 0.55, 95% CI 0.31–0.97) were demonstrated as significant prognostic factors.
Conclusion: In breast cancer patients, overexpression of LOXL-2 is a poor prognostic factor for overall survival and distant metastasis-free survival.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-14.
Abstract P2-05-19: Pathway-based analysis of breast cancer
Authors: Song D , Cui M , Fan Z , Yang Y , Xue L , Zhang DY , Ye F 
Published: August 2014

Abstract
Objective: Although HER2 and ER pathways are predominant pathways altered in breast cancer, it is now well accepted that many other signaling pathways are also involved in the pathogenesis of breast cancer, especially in triple negative breast cancer. The understanding of these additional pathways may assist in identifying new therapeutic approaches for breast cancer.
Methods: 13 invasive ductal carcinoma tissues and 5 benign breast tissues were analyzed for the mRNA expression level of 1243 cancer pathway-related genes using SmartChip (WaferGen, CA), a real-time PCR-base method. In addition, the levels of 154 cancer pathway-related proteins and phosphoproteins were measured using our innovative Protein Pathway Array.
Results: Out of 1,243 mRNAs, 68.7% were detected in breast cancer and 73 mRNAs were statistically significant between benign and cancer tissues. Of these mRNAs, 105 only expressed in breast cancer tissues and 33 mRNAs only expressed in normal breast tissues. Out of 154 proteins and phosphoproteins, 39% were detected in cancer tissues and 50 proteins were significantly differentiated between tumor and normal tissues. Interestingly, only 3 genes (CDK6, Vimentin and SLUG) showed decrease of both protein and mRNA. Six proteins (BCL6, CCNE1, PCNA, PDK1, SRC and XIAP) showed differentially expressed between tumor and normal tissues but no differences were observed at mRNA levels. Analyses of mRNA and protein data using Ingenuity Pathway Analysis showed more 15 pathways were altered in breast cancers and 6 of them shared between mRNAs and proteins, including p53, IL17, HGF, NGF, PTEN and PI3K/AKT.
Conclusion: There is a broad dysregulation of various pathways in breast cancer both at protein levels and mRNA levels. It is important to note that mRNA expression does not correlate with protein level, suggesting that different regulation mechanisms between proteins and mRNAs.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-19.
Abstract P2-10-20: A tumor DNA complexity index is an independent predictor of survival in a dataset of 1950 breast cancers; a METABRIC group study.
Authors: Vollan HKM , Rueda OM , Børresen-Dale A-L , Aparicio S , Caldas C 
Published: August 2014

Abstract
Background: Cancer genomes undergo substantial alterations during carcinogenesis. Patterns of such rearrangements differ with respect to cancer subtypes and may affect crucial parts of the genome. DNA based markers would make clinical implementation more feasible as markers based on RNA expression are challenging due to the intrinsic problem of RNA stability and volatility in expression patterns. Complex genomic rearrangements in breast cancer genomes, quantified by the complex arm-wise aberration index (CAAI), have previously been shown to be of prognostic value. However this finding has not been validated in independent large-scale breast cancer cohorts or compared with other molecular predictors.
Methods: A total of 1950 breast carcinomas from the METABRIC cohort with log term follow up were included in this study. Microarray based copy number and expression data from fresh frozen primary tumors were available. Cases were classified as CAAI positive if at least one complex event was present in the tumor genome. The clinical end points were breast cancer specific survival (BCSS) and overall survival (OS).
Results: A total of 33 % of breast cancer cases were CAAI positive with a Cox proportional hazard ratio (HR) of 1.78 (95% CI, 1.49–2.12) for BCSS. Using multivariate Cox regression the adjusted HR for BCSS of 1.42 (95% CI, 1.12–1.80) and 1.44 (95% CI, 1.02–2.03) in estrogen receptor positive (ER+) and estrogen receptor negative breast cancers, respectively. Gene expression classifiers based on OncotypeDX and MammaPrint were not independently prognostic in the ER− subset. Significant difference in survival was both seen in patients that received systemic treatment, and in patients that did not.
Conclusions: DNA based prognostic profiling is a robust method for both fresh frozen and FFPE tumor material. This study shows that complex genomic alterations of tumor DNA, measured as CAAI, is an independent predictor of survival in breast cancer, in both ER+ and ER− disease in a large scale breast cancer cohort with long term follow up. The effect seems unrelated to systemic endocrine treatment or chemotherapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-20.
Abstract P2-11-08: Feasibility of Enrollment Into a Survivorship Care Plan Study at Initial Diagnosis
Authors: Bulloch KJ , Irwin M , Chagpar A , Sanft T 
Published: August 2014

Abstract
Introduction: The Institute of Medicine currently recommends all cancer survivors be provided survivorship care plans (SCPs) to aid them in their transition from cancer patient to cancer survivor. To our knowledge, there are very few comprehensive cancer treatment centers that report having a system that insures all patients will receive SCPs. One of the chief obstacles in broadly providing care plans is logistical; not all breast cancer patients undergo the same treatment progression and thus it is difficult to identify a suitable time after which the provider should distribute SCPs. Though adjuvant treatment pathways differ between patients, nearly all breast cancer patients receive surgery and thus surgery clinics could provide an opportunity to identify the majority of patients who will eventually be cancer survivors. The purpose of this study is to assess the feasibility of providing SCPs to breast cancer survivors by enrolling them at the postoperative visit and tracking them prospectively throughout their treatment.
Methods: 75 English-speaking women over the age of 18 with stage I-III breast cancer were enrolled at their postoperative appointment. The participants' treatment progress was tracked through the electronic medical record; the treatment information was abstracted from the records and used to create treatment summaries. Once treatment was completed, participants received the SCP during one of their scheduled follow-up appointments.
Results: Accrual occurred during 42 clinic days between April 2011 and February 2012. During that time, there were 129 postoperative appointments for patients with a diagnosis of breast cancer. 54 did not meet the eligibility requirements; 46 were DCIS, three had metastatic cancer, and five did not speak English. Of the patients who met the eligibility requirements 100% agreed to participate. Characteristics are shown in Table 1.

Only 39.4% of participants received both chemotherapy and radiation and 9.6% of our participants received their adjuvant therapy outside of Smilow Cancer Center.
Conclusion: Women recently diagnosed with breast cancer are interested in receiving survivorship care plans after treatment, as demonstrated by 100% accrual rate of eligible patients approached in the postoperative visit. The postoperative visit in a surgical clinic may provide the starting point for tracking a patient through treatment.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-08.
Abstract P2-11-10: Prospective memory impairment in early breast cancer survivors: Finally homing in on the real deficit?
Authors: Verma S , Collins B , Song X , Bedard M , Paquet L 
Published: August 2014

Abstract
Background There is still much debate about the impact of early breast cancer (EBC) treatment on memory functioning. One limitation of existing studies is that they are based on neuropsychological testing procedures which may not be sensitive enough to detect memory problems as encountered in daily life. In fact, no study has objectively assessed everyday memory performance in EBC. One crucial aspect of using memory in daily activities is to remember to do something at an appropriate time in the future without being asked to do so-defined as “prospective memory” (PM). Despite its importance for daily functioning, little is known about PM in EBC patients. Thus, we investigated whether EBC survivors who were within 1 year of having completed adjuvant chemotherapy have PM impairment in comparison to age-matched healthy controls. In addition, we evaluated the contributions of fatigue and depression to PM functioning.
Methods We undertook a cross sectional quantitative case-control study (n = 80) comparing EBC patients from the Ottawa Hospital Regional Cancer Centre with age and education-matched healthy controls from the community. A standardized test of PM (Memory for Intention Screening Test) was administered to both groups. Impairment was defined as a score that fell 2 standard deviations below the mean performance of the control group. Standardized measures of depression (CESD) and fatigue (Fact-F) were also completed.
Results Age was well balanced between the groups (case and control mean age 54y, p = .84). EBC patients performed more poorly than controls on the PM test (p &lt; .001) and had a significantly higher rate of impairment (23% vs. 5%, McNemar χ2, p &lt;.01, odds ratio=5.5, 95% CI=1.7745 to 17.1473). A series of hierarchical regressions showed that patients PM performance was affected by fatigue (p &lt;.05), but not depression (p = .51).
Conclusions The results demonstrate reduced memory performance in EBC survivors, with a specific impact on PM. Women who complain of ‘chemo fog’ should be evaluated carefully for PM deficits and their concerns should be acknowledged. An important finding from this study is the demonstration that fatigue is associated with memory deficits when memory as used in everyday life is evaluated. This finding which is suggestive of a common mechanism involved in fatigue symptoms and everyday memory disturbances raises the possibility that interventions targeted at improving fatigue may also improve memory functioning and quality of life in EBC survivors. Further longitudinal studies should be conducted to critically evaluate the role of chemotherapy by assessing PM before the initiation of chemotherapy and in EBC patients receiving only adjuvant hormonal therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-10.
Abstract P2-12-04: Music Therapy Reduces Radiotherapy-Induced Fatigue in Patients with Breast or Gynecological Cancer: A Randomized Trial
Authors: Freitas NMA , Silva TRMA , Freitas-Junior R , Paula Junior W , Silva DJ , Machado GDP , Ribeiro MKA , Carneiro JP 
Published: August 2014

Abstract
BACKGROUND: Fatigue is a frequent side effect of radiotherapy, and may interfere with self-esteem, social activities, and quality of life. The authors investigated the influence of music therapy (MT) on the reduction of fatigue in women with breast or gynecological malignant neoplasia during radiotherapy.
METHODS: Randomized controlled trial (control group-CG and music therapy group-MTG) to assess fatigue, quality of life using the Functional Assessment of Cancer Therapy (FACT-F and FACT-G) version 4 and symptoms of depression using Beck Depression Inventory (BDI) in women undergoing radiotherapy in three distinct moments (during the first and the last week of radiotherapy, and on the week of the intermediary phase). Individual 30–40 minute sessions of music therapy were offered to participants of the MTG.
RESULTS: In this study, 164 women were randomized and 116 (63 CG and 53 MTG) were included in the analyses, with mean age of 52.9 years (CG) and 51.85 years (MTG). Participants in the MTG had an average of 10 MT sessions, during the study. FACT-F results were significant regarding Trial Outcome Index (TOI), synthesis of the Physical and functional well-being areas of FACT-F (p = 0.011), FACT-G (p = 0.005), FACT-F (p = 0.001) for MTG compared with CG. The depressive symptons were reduced to the minimum levels in the MTG (p = 0,005) with risk reduction of 74% (RR = 0,26; CI 0,10–0,70).

CONCLUSIONS: Individual MT sessions are effective to reduce fatigue related to cancer and symptoms of depression, as well as to improve quality of life for women with breast or gynecological cancer undergoing radiotherapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-04.
Abstract P2-12-13: Results of randomised controlled phase II study (KBCSG02 trial) of the efficiency of palonosetron, aprepitant, and dexamethasone for day1 with or without dexamethasone on days2 and 3.
Authors: Kosaka Y , Sengoku N , Kikuchi M , Nishimiya H , Enomoto T , Kuranami M , Watanabe M 
Published: August 2014

Abstract
Background: Emesis is one of the major non-hematologic toxicity caused by chemotherapy. The control of Chemotherapy Induced Nausea and Vomiting (CINV) is conducted to a life lengthening. Recently, CINV is controlled by the second generation 5-HT3 receptor blocker (Palonosetron; PALO) and a NK-1 receptor antagonist (Aprepitant; APR). It has been shown that dexamethasone (DEX) with 5-HT3 receptor blocker improves acute/delayed CINV. However, it has not been determined the medication schedule of DEX with PALO and APR. The purpose of this study is evaluated the efficiency of palonosetron, aprepitant and dexamethasone for day1 with or without dexamethasone on days2 and 3.
Methods: Breast cancer patients who administered anthracyclin drug regimen have been eligible from April, 2011 to June, 2012. The patients were randomised to group A (PALO/APR/DEX one day) and group B (PALO/APR/DEX three days). Eighty patients was estimate as study samples. The primary endpoint was a complete response (CR) rate of vomiting, the secondary endpoint was a complete control (CC) rate of vomiting.

Results: Forty patients were enrolled in this study, and patient recruitment is continued. CR rate was no significant difference in both groups (76.9% of group A, 73.3% of group B). CC rate of group A (61.5%) did not show inferiority compared with group B (40.0%).
Conclusions: In this current study, we suggest that one day dexamethasone treatment could reduce enough the emesis of high emetogenic chemotherapeutic agents.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-13.
Abstract P3-01-05: The Role of Mammographic Calcification in the Neo-adjuvant Therapy of Breast Cancer Imaging Evaluation
Authors: Li JJ , Chen CM , Di GH , Wu J , Lu JS , Shao Z-M 
Published: August 2014

Abstract
Aim: To evaluate the relationship between malignant appearance of mammographic calcification and breast cancer pathological features, and to explore the predictive value of calcification appearances and morphology changes in neo-adjuvant setting.
Methods: 419 patients with operable breast cancer received neo-adjuvant therapy between 2008.2 and 2011.8 in Shanghai Cancer Hospital. Core needle biopsy was conducted before preoperative therapy to determine cancer and achieve pathological features. Mammogram (MG), ultrasound and breast MRI were routinely done prior to therapy and prior to surgical operation. We conducted a detailed analysis of MG images in patients with malignant calcification, recorded the morphology, distribution, range, density, diameter and number of the calcification.
Results: 419 patients enrolled, 108 patients (25.8%) showed malignant calcification in MG, 6 patients missed the first MG before therapy. 214 patients were Luminal A, 95 were Luminal B, 64 were Her2 positive and 46 were triple negative, the pCR rate was 14%, 30.5%, 53%, 43.5% respectively. Patients with malignant calcification have more ER positive (81.5% vs. 71.7%, p = 0.045) and HER2 positive (51.8% vs. 33%, p = 0.001) diseases. The pCR rate was 26% in patients with malignant calcification and 28% in patients without, p = 0.8.

Different morphology shapes showed similar pCR rate, p = 0.89. Casting-type had a higher pCR rate 45.8%, compared with 20% in crushed stone-like and 16.7% in powderish, p = 0.031. Range more than 5cm had a higher pCR rate, 40.7% vs. 20%, p = 0.034. Density, diameter and number of the calcification did not reach statistical difference, however high density, diameter &gt;1mm and number &gt;20 per cm2 showed a trend of higher pCR rate. Patients with diameter ≤0.5mm had a higher lymphatic vascular invasive rate 51.4%, compared to diameter≤1mm (26.8%) and diameter &gt;1mm (22.7%), p = 0.03. Morphology and distribution of calcification did not change obviously. Less than 30% patients showed changes in range, number or density, no relationship with pCR rate.
Conclusion: Patients with malignant calcification are more likely to have ER positive and Her2 positive diseases. MG should be considered the standard prior to the start of therapy, the distribution and range of the calcification may predict pCR rate. Calcification appearance does not change significantly after neo-adjuvant therapy, therefore MG is not an appropriate method for efficacy evaluation. But MG before surgery is still useful to identify the extent of surgery, especially in breast conserve therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-05.