bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing ER, PgR, and HER2 status between primary and recurrent breast cancer.
Authors: Matsumoto Akiko , Takahashi Maiko , Hayashida Tetsu , Hirose Shigemichi , Jinno Hiromitsu , Kitagawa Yuko 
Published: February 2017

92 Background: Estrogen receptor (ER), progesterone receptor (PgR), and HER2 status are important biological markers for making decisions about breast cancer treatments. Although changes of hormone receptor (HR) and HER2 status with recurrence of breast cancer are clinically experienced, the frequency of discordance and clinical significance are still unknown. Thus, we investigated ER, PgR, and HER2 status with primary tumors and recurrent lesions, and assessed discordance rates and prognosis. Methods: We retrospectively identified recurrent breast cancer patients who had biopsies or resections of recurrent lesions between January 2007 to April 2012 at Keio University Hospital. HR status was assessed by immunohistochemistry (IHC) and determined using the Allred score. HR status was defined as positive when score was 3 and more. HER2 status was assessed by IHC and fluorescence in situ hybridization (FISH) analysis. We defined HER2 positivity as 3+ staining intensity by IHC or the presence of HER2 gene amplification by FISH. Results: Among 32 recurrences, 40% (13) were loco-regional recurrences (LLR) and 60% (19) were distant metastases (DM) (lung 14; liver 3; brain 1; pleura 1). Discordance rates in ER, PgR and HER2 status between the primary tumors and the recurrence lesions were 12.5%, 31.3%, and 13.8%, respectively. The most common change was loss of PgR. Changings from negative to positive in ER, PgR and HER2 status were found in 6.3%, 3.1%, and 3.4% of the patients, respectively. All gains were found in distant metastases. Discordance in ER and HER2 were more common in DM (15.8% and 17.6%) comparing with LRR (7.7% and 8.3%). Loss of HR status was not associated with a shorter time to progression (TTP) (ER: 19.3 vs. 8.5 months, p=0.185; PgR: 4.4 vs. 11.5 months, p=0.907). Patients with discordant HER2 status had significantly shorter TTP than with concordant status (0.9 vs. 11.5 months, p=0.012). Conclusions: Discordance of biological markers between primary and recurrent breast cancers were seen in 10-30%. Although HR discordance was not associated with prognosis, patients with HER2 discordance had poorer TTP. Tissue confirmation should be considered for making effective treatment decisions in recurrent breast cancer.
Proactive approach to risk reduction and early detection of breast cancer-related lymphedema.
Authors: Fu Mei R. , Guth Amber , Kleinman Robin , Cartwright Francis , Axelrod Deborah M. 
Published: February 2017

95 Background: Advances in surgery and post-operative treatment continue to reduce the incidence of late effects of cancer treatment such as lymphedema. Yet, many breast cancer survivors still face considerable post-operative challenges as a result of developing lymphedema. The purpose of this study was to preliminarily evaluate an educational and behavioral program “The Optimal YOU” to enhance lymphedema risk reduction among patients with breast cancer. The intervention focuses on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal BMI as well as preoperative and subsequent follow-up assessment of limb volume changes and symptoms. Methods: A quasi-experimental design with repeated-measures was used to assess outcomes of The Optimal YOU program at pre-operative baseline, post-operative, 6-month, and 12-month follow-up. A total of 147 patients newly diagnosed with breast cancer were recruited and received the program. The program outcome data include lymph volume changes by infra-red perometer-S350, lymphedema-related symptoms by Lymphedema Symptom Experience Index, and body mass index (BMI) by Bioimpedance DF50. Results: Among the 147 patients, 141 patients completed the study (4% attrition rate). Majority (94%) of patients maintained preoperative limb volume and improved their symptom experience at 12-month follow-up. During the 12-month study period, only five patients (6%) developed lymphedema and were referred for lymphedema treatment. At 12-month follow-up, among the five patients who developed measurable lymphedema, two patients’ limb volume returned to pre-operative level without compression therapy only by maintaining exercises of The Optimal YOU to promote daily lymph flow. About 80% of patients maintained or improved their preoperative BMI. Conclusions: The study shows that proactive approach to implementing The Optimal YOU program is effective to risk reduction and early detection of breast cancer-related lymphedema by focusing on preventing inflammation-infection, promoting lymph drainage, and maintaining optimal BMI.
Incidence complications following sentinel lymph node biopsy or axillary lymph node dissection after breast cancer surgery.
Authors: Bello Marcelo Adeodato , Bergmann Anke , Dias Ricardo , Thuler Luiz Claudio Santos , Tonellotto Fabiana , Pinto Renata Reis , Fabro Erica 
Published: February 2017

97 Background: To reduce arm morbidity the sentinel lymph node biopsy was implemented in the breast cancer treatment. The aim of this study was to investigate the arm morbidity after sentinel lymph node biopsy or axillary lymph node dissection. Methods: This is a prospective cohort study of women who underwent surgical treatment of breast cancer at a single institution. Arm and shoulder morbidity were measured before, 1 and 6 months after the operation. Analyses were performed to compare morbidity between sentinel lymph node biopsy (SLND) and axillary lymph node dissection (ALND). This study obtained approval from the National Cancer Institute research and ethics committee. Results: Were included 203 patients and, during the study, 6 were excluded and there was 23 losses of follow-up. The average age of women was 58 years (DP=13). SLND was made in 31,6% with an average of 3 lymph nodes removed. Among those submitted to ALND, the average lymph node removed was 18 (p<0.0001). After 45 days of surgery, the incidence of arm morbidity was: 23% of shoulder restriction (ALND 22%, SLND 1%, p<0.001); 28% of axillar web syndrome (ALND 24%, SLND 4%, p<0.001); 38% of seroma (ALND 32%, SLND 6%, p<0.001); 5% of arm edema (ALND 4%, SLND 1%, p<0.001). In the final evaluation occurred 6 months after the surgery, it was observed de following incidence: 4% of shoulder restriction (ALND 3%, SLND 1%, p=0.371); 18% of arm pain (ALND 12%, SLND 6%, p=0.460); 18% of axillar web syndrome (ALND 16%, SLND 2%, p<0.002); 5% of arm edema (ALND 4%, SLND 1%, p=0.417). Conclusions: After 45 days of surgery, patients with SLND has less arm morbidity compared with patients submitted to ALND. After 6 months, it was observed less incidence of arm symptoms and only axillary web syndrome were more incident in patients with axillary dissection.
Evaluation of circulating biomarkers of bone metastases in early-stage breast cancer.
Authors: Dean-Colomb Windy Marie , Hess Kenneth R. , Young Elliana J. , Gornet Terrie , Handy Beverly Carol , Moulder Stacy L. , Ibrahim Nuhad K. , Pusztai Lajos , Booser Daniel J. , Valero Vicente , Hortobagyi Gabriel N. , Esteva Francisco J. 
Published: February 2017

10 Background: Bone is the preferred site for metastases of breast cancer, affecting approximately 70% of women with advanced disease. N-terminal of procollagen type 1 (P1NP), c-terminal peptide crosslinks (CTX), osteocalcin (OC), and interleukin-6 (IL-6) are markers of bone turnover that may have clinical utility as predictors of breast cancer recurrence in the bone. Methods: Serum was collected prior to treatment from 162 patients with stage I-III and 83 patients with stage IV breast cancer from 09/2001 to 12/2008. Serum levels of P1NP, CTX, OC, and IL-6 were determined using the Roche’s Elecsys 2010 automated immunoassay system. Correlations of biomarker levels with stage and with time to bone metastases development were assessed with Cox proportional hazards regression analysis and the Kaplan-Meier method. Results: Patients with stage IV at the time of diagnosis had higher levels of serum P1NP (p<0.0001) and CTX (p<0.0001) compared with stage I-III patients. Fifty-five of the 162 patients with stage I-III breast cancer subsequently developed metastatic disease. Baseline P1NP level ≥ 75 ng/mL predicted time to development of bone metastases in patients with stage I-III breast cancer (hazard ratio = 2.7, 95% confidence intervals = (1.2, 6.0), p = 0.031), even after adjusting for clinical factors (p = 0.019). Baseline P1NP level also correlated with OS when it was modeled as a quadratic polynomial (on the log scale) with patients with P1NP level ≥ 75 ng/mL having a worse overall survival (hazard ratio = 3.3, 95% confidence intervals = (1.5, 7.3),p = 0.0036. Conclusions: In patients with stage I-III breast cancer, serum P1NP levels >75 ng/mL prior to definitive treatment correlated with shorter time to development of bone metastases and shorter overall survival rate. Baseline serum levels of IL-6, CTX and osteocalcin did not correlate with development of bone metastases.
Funding of biomarker, imaging, quality-of-life (QOL), and cost-effectiveness analysis (CEA) studies by NCI.
Authors: Petryshyn Ray A. , Seidel Geoffrey David , Prindiville Sheila Ann 
Published: February 2017

104 Background: NCI’s purpose for the Biomarker, Imaging, and QOL Studies Funding Program (BIQSFP) is to ensure that the most important, scientifically meritorious biomarker, imaging, QOL, and/or CEA studies can be initiated in a timely manner in association with NCI clinical trials. BIQSFP studies are embedded in selected large, randomized phase II treatment trial concepts with a control arm and an integral study(ies), along with integral and/or integrated studies associated with phase III treatment trials, cancer prevention trials, and primary symptom management trials. Methods: BIQSFP provides opportunities to enhance clinical outcomes by validating targets, reducing morbidity, predicting treatment effectiveness, identifying populations that may better benefit from treatment, improving clinical trial accrual and retention, and modifying standards of care. BIQSFP applications are accepted from NCI Cooperative Groups and Community Clinical Oncology Programs. Integral components must be performed in order for the trial to proceed. Integral studies have the highest funding priority. Integrated components are clearly identified as part of the clinical trial from the beginning, are intended to identify or validate (in the patient population of interest) assays/tests/QOL tools that are planned for use in future trials, are performed in real time, and include complete plans for specimen collection, laboratory measurements, and statistical analysis. Integrated studies in general should not be exploratory but rather should be designed to test a hypothesis, not simply to generate hypotheses. Results: Since 2009, 36 BIQSFP funding applications have been reviewed with most evaluations via NCI’s Scientific Steering Committees (http://ccct.cancer.gov/). Twenty studies have been approved for BIQSFP funding. Conclusions: BIQSFP information presented in the poster includes scope of activity, process for application and evaluation, and funded projects (http://biqsfp.cancer.gov/). Funded by NCI Contract No. HHSN261200800001E.
Cell-free microRNA expression profiles in malignant effusion associated with patient survival in non-small cell lung cancer.
Authors: Wang Tingting , Liu Baorui , Hou Yayi 
Published: February 2017

13 Background: MicroRNAs (miRNAs) expression is altered in cancer cells, and miRNAs could serve as diagnostic and prognostic biomarker for cancer patients. This study was designed to analyze circulating miRNAs expression in the malignant pleural effusion (MPE) and their association with patient survival in non-small cell lung cancer (NSCLC). Methods: Pleural effusion from 184 patients with NSCLC and MPE were collected. MiRNA microarray and bioinformatics interpretation were used to evaluate miRNA expression profiles in 10 NSCLC patients with different survival prognosis. Associations were validated in 184 patients (randomly classified into training and validation set with equal number in each group) using quantitative RT-PCR. Risk scores were formulated based on the expression signature of miRNAs. Clinical data, such as patient survival, were collected for correlation analysis. Results: Thirty-three miRNAs were found to be altered more than two-fold by microarray in malignant effusions between longer-survival and shorter-survival groups, and levels of five miRNAs (miRNA-93, miRNA-100, miRNA-134, miRNA-151, and miRNA-345) were significantly associated with overall survival. High expression of miR-100 and low expression of miRNA-93, miRNA-134, miRNA-151, and miRNA-345 were associated with poor survival in both the training and validation cohort. Patients with high risk scores had overall poor survival compared to the patients with low risk scores. Risk score was an independent predictor of patient survival. Conclusions: Expression patterns of miRNAs are systematically altered in MPE of patient with NSCLC. The five miRNA signature from the effusion may serve as a predictor for the overall survival of patients with lung cancers.
MicroRNA in biofluids—Robust biomarkers for disease, toxicology, or injury studies: The case of minimally invasive colorectal cancer detection.
Authors: Mouritzen Peter , Nielsen Søren Jensby , Wrang Teilum Maria , Blondal Thorarinn , Andreasen Ditte , Tolstrup Niels 
Published: February 2017

20 Background: MicroRNAs function as post-transcriptional regulators of gene expression. Their high relative stability in common clinical source materials (FFPE blocks, plasma, serum, urine, saliva, etc.) and the ability of microRNA expression profiles to accurately classify discrete tissue types and specific disease states have positioned microRNAs as promising new biomarkers for diagnostic application. Furthermore microRNAs have been shown to be rapidly released from tissues into the circulation with the development of pathology. Methods: Thousands of biofluid samples were profiled including blood derived plasma/serum and urine using a genome-wide LNA-based microRNA qPCR platform, which has unparalleled sensitivity and robustness even in biofluids with extremely low microRNA levels. Only a single RT reaction is required to conduct full miRNome profiling thereby facilitating high-throughput profiling without the need for pre-amplification. Results: Normal reference ranges for circulating microRNAs were determined in several biofluids, allowing development of qPCR arrays containing only relevant microRNA subsets present in various biofluids together with tissue specific microRNA markers. Procedures were developed to control pre-analytical variables, for quality checking and qualifying biofluid samples in particular serum and plasma but also urine and other biofluids. An extensive QC system was implemented in order to secure technical excellence and reveal any unwanted bias in the dataset. We currently screen and validate microRNAs biomarkers for cancer with the aim of developing minimal invasive tests to be applied in early detection population screens. Conclusions: The qPCR panels support development of robust biomarkers in disease, toxicology, and injury studies. We will demonstrate how panels may be quickly and robustly applied in biomarker discovery/validation projects using the specific case early detection of colorectal cancer in blood. Close attention is required on pre-analytical parameters. Hemolysis and cellular contamination affect miRNA profiles in biofluids and control is required.
Role of M402, a novel heparan sulfate mimetic, in pancreatic cancer cell invasion and metastasis: Inhibition of the Sonic Hedgehog pathway and heparanase activity.
Authors: Galcheva-Gargova Zoya , Chu Chia Lin , Long Alison , Duffner Jay , Holte Kimberly , Schultes Birgit Corinna 
Published: February 2017

25 Background: M402 is a novel heparin sulfate mimetic that binds to multiples growth factors, adhesion molecules, and cytokines to inhibit tumor angiogenesis, progression, and metastasis in nonclinical studies. We investigated if M402 could modulate tumor-stroma interactions in pancreatic cancer by inhibiting the Sonic Hedgehog (Shh) pathway as well as inhibit the activity of the extracellular matrix degrading enzyme, heparanase. Methods: Surface plasmon resonance (SPR) was used for analysis of M402 binding to Shh in vitro. A cell based Gli-1 reporter assay was implemented to assess the effect of M402 on Shh signaling. Immunohistochemistry and RT-qPCR were utilized to investigate M402’s effect on Shh activity in an orthotopic Capan-2 model in nude mice. The effect of M402 on heparanase activity in vitro and on Capan-2 tumor samples isolated from treated and untreated mice was measured using an HTRF-FRET assay. Results: There was specific binding of M402 to Shh in vitro. Additionally, Shh signaling was inhibited in the presence of M402. Immunohistochemistry and RT-qPCR of Capan-2 tumor samples from animals treated with M402 also demonstrated reduction of Shh signaling via Gli, its targeted transcription factor. The degree of inhibition of heparanase activity, as measured in the HTRF assay, was affected by the size, structure, and sulfation pattern of the different heparin sulfate mimetics evaluated. M402 was the most potent inhibitor of heparanse activity in vitro from all compounds tested. In addition, treatment with M402 inhibited heparanase activity in the pancreatic tumor lysates in a dose-dependent manner. Conclusions: M402 was shown in nonclinical studies to modulate tumor-stroma interactions involved in the metastatic, invasive, and desmoplastic pathways by simultaneously inhibiting two distinct pathways: Shh signaling and the activity of heparanase. M402 regulates a variety of polysaccharide-based binding proteins, which provides a rationale for the clinical investigation of M402 in a range of cancers.
A nanofluidic immunoassay system to develop proteomic responsive biomarkers in non-small cell lung cancer.
Authors: Chen Jin-Qiu , Lee Jih-hsiang , Herrmann Michelle , Wang Yisong , Park Kang-seo , Heldman Madeleine , Goldsmith Paul , Giaccone Giuseppe 
Published: February 2017

27 Background: Molecular targeted therapy is widely used to treat non-small cell lung cancer (NSCLC). However, errors in predicting response to targeted therapies are 20-30%, based on sequencing or FISH, and patient specimen are at times not sufficient for conventional protein technologies. Developing clinically feasible proteomic biomarkers may be valuable to identify patients who may benefit from targeted therapy. Methods: NanoPro technology (ProteinSimple), is a capillary-based isoelectric-focusing (IEF) immunoassay system, which detects and quantifies multiple protein phosphorylation isoforms that are not readily assessed by traditional immunoassays. The platform only uses nanograms of protein for analysis. Results: We studied dynamic phosphoprotein activities in NSCLC cells (PC9, H827, H4006, H2122 and H322) treated with EGFR or/and MEK inhibitors. In MEK inhibitor (PD325901) treated cells, NanoPro showed that the drug efficiently inhibited Erk phosphorylation, and also revealed a complex MEK response profile which was not detectable by Western blotting, demonstrating its on-target effect. NanoPro also identified a MEK2 signature that associated with erlotinib sensitivity and distinguished erlotinib sensitive from resistant cells. This MEK2 signature was further confirmed in acquired resistant cells to erlotinib (H827R, H4006R). In a H827 xenograft study, NanoPro was able to detect and distinguish human Erk1 isoform from mouse Erk1 based on their pI difference, and clearly demonstrated that erlotinib effectively inhibited Erk phosphorylation in human xenograft cancer cells but not in surrounding mouse stromal cells. We further demonstrated that Nanopro could monitor erlotinib and AZD2644 response in a KrasG12C NSCLC patient (NCT01229150) by profiling 18 signaling molecules with as little as 4ug tumor material. Conclusions: NanoPro provides a valuable platform to monitor signaling response to targeted therapy. Nanopro assesses protein phosphorylation both qualitatively and quantitatively using small sample size, thus creates new opportunities for pharmacodynamic biomarker assessment in clinical studies.
The analytic validation of prostate-specific mRNA detection in whole blood by RT-PCR as a prognostic biomarker for patients with castration-resistant prostate cancer (CRPC).
Authors: Danila Daniel Costin , Anand Aseem , Heller Glenn , Wan Mingliang , Zehnder Matthew , Khanin Raya , Schultz Nikolaus , Fleisher Martin , Lilja Hans , Scher Howard I. 
Published: February 2017

36 Background: To estimate the association between molecular biomarkers and outcomes, robust assays are needed before clinical qualification. Although tumor specific transcripts detected in blood by PCR have been associated with outcome, an analytically validated platform enabling detection of CTC-associated transcripts in clinical settings remains to be identified. Here we explore the efficacy of detecting a panel of prostate specific transcripts in CRPC. Methods: Blood was collected from 97 pts with progressive CRPC in PAXgene tubes (2.5 ml) for total RNA extraction using PAXgene Blood RNA Kit. Five genes expressed in prostate but not in nucleated blood cells were analyzed by RT-PCR. We used Fluidigm Dynamic Array platform to analytically validate RT-PCR assays for KLK3, KLK2, HOXB13, GHRL2, and FOXA1 transcripts. Each PCR-reaction was run in 6 replicates, detection thresholds for each gene were chosen by ROC analysis of an independent set of 56 CRPC patients versus 51 healthy volunteers, and results were reported as transcripts present or absent. CellSearch reported CTC number/7.5 ml of blood drawn into CellSave tube. Results: Prostate specific transcripts (≥ 2 genes) were detected in 52/97 (54%, 95% CI 43-64%) of patients with progressive CRPC studied with a median survival time of 17 months (95% CI: 13.8, 23.5). 40/45 CRPC-patients with ≥ 5 CTC and 15/52 CRPC patients with < 5 CTC had transcripts present in blood. Similar to CTC enumeration, transcript detection predicted overall survival in proportional hazards models that included LDH dichotomized at above and below 300. The predictive accuracy (CPE) of PCR detection + LDH was 0.785 (SE 0.036), comparable to CTC-enumeration + LDH (0.796, SE 0.035). Conclusions: Detecting prostate specific mRNA in whole blood using validated RT-PCR assays, applicable to larger CRPC cohorts, provides prognostic biomarkers that predict overall survival. The clinical utility in monitoring treatment will be prospectively explored. [Table: see text]