bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P3-01-04: Surgical management of mammographic microcalcification is improved by full field digital mammography (FFDM)
Authors: Bundred SM , Zhou J , Hurley E , Wilson M , Morris J , Bundred NJ 
Published: August 2014

Abstract
Background: Preoperative diagnosis of impalpable breast lesions correlates closely with the number of surgical procedures required for treatment. Correct diagnosis of mammographic microcalcification as DCIS or invasive cancer is important because lesions upgraded to malignant diagnosis at surgery require repeat surgical procedures in 44% of cases (BASO Audit 2011).
Methods: To determine the impact of FFDM (FFDM only since April 2010) on diagnostic accuracy, positive predictive value (PPV) and surgical management of MM. Screening and symptomatic women with mammographic microcalcification (n = 1125) in one visit were reviewed. Demographic information; pre and post operative diagnosis and number of surgical procedures were recorded for pre FFDM (8/ 2007 to 3/2010: n=710) and post FFDM (4/2010 to 5/2011: n=413).
Results: Overall 299 (106 invasive) and 144 (62 invasive) malignant lesions were diagnosed before and after FFDM introduction.

Reduction in PPV of biopsy for mammographic microcalcification was observed (SFM PPV 42.6%: FFDM PPV 34.6% (p &lt; 0.01)). Upgrade of B3/4 lesions reduced (SFM 50% (21/42) vs. FFDM 21.7% (5/23): p &lt; 0.05) and pre-operative diagnosis of DCIS improved (88.6% vs. 94%) using digital mammography.
Correct histological pre-operative diagnosis permitted a single therapeutic operation for 76.7%, compared to 66% of mammographic microcalcification where pre-operative diagnosis was inaccurate (p &lt; 0.001).
Re-excision rates for DCIS lesions &gt;20mm fell from 34.1% (60/176) to 21.1% (19/90) with FFDM (p &lt;0.05).
Conclusions: Correct pre-operative diagnosis of mammographic microcalcification using FFDM has reduced second therapeutic procedures for mammographic microcalcification, decreased upgrade of B3/4 lesions at diagnostic surgery, but increased benign non-operative biopsies for mammographic microcalcification.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-01-04.
Abstract P3-02-01: Mammographic Screening: Good Prognosis Tumor Biology in Screen-detected Breast Cancers
Authors: Drukker CA , Schmidt MK , Rutgers EJT , Cardoso F , Kerlikowske K , Esserman LJ , Slaets L , Bogaerts J , van't Veer LJ 
Published: August 2014

Abstract
Introduction After the introduction of population-based screening breast cancer incidence increased while breast cancer mortality declined. Our previous analyses suggested screen detection might be associated with a higher likelihood of a biologically low risk or even ultralow risk tumor assessed by the 70-gene signature (MammaPrint™). (Ultralow 70-gene signature defined as indexscore &gt; 0.6, no distant metastasis observed at 5 years in the original 78 patients with no adjuvant systemic treatment.) The aim of this study is to determine the proportion of biologically low and ultralow risk tumors among the screen-detected tumors. Second, to evaluate the impact of analog versus the more sensitive digital screening technique on the biology of tumors detected.
Methods All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007–2011, who were invited for the Dutch screening program (biennial, age 50–75), were included (n = 1381). The proportions of 70-gene signature high, low and ultralow risk were calculated for patients with screen detected (n = 694), interval (n = 366), and symptomatic, non-screening (n = 321) carcinomas, taking into account analog vs. digital technology. Co-variants, such as age, tumor size, histological type, ER, progesterone receptor (PgR) and HER2/neu-oncoprotein (ERBB2) will be included in a multinominal logistic regression model to assess both confounding and effect modification by technology type; these data are pending and will be available during SABCS 2012.
Results Among the screen-detected tumors, 33% had a high risk 70-gene signature tumor and 67% had a low risk tumor (table 1). A significant difference was seen between the screen-detected carcinomas and interval carcinomas (p X2 test = 0.001) in all 70-gene signature risk groups. Among the screen detected carcinomas, 41.5% was detected using analog mammography and 58.5% was detected using digital mammography. Analog mammography detected 26.4% high risk, 31.9% low risk and 41.7% ultralow risk tumors. This is significantly different using digital mammography (p X2 test = 0.001), which detected 37.7% high risk, 32.8% low risk and 29.6% ultralow risk tumors.

Conclusion Screen detection was found to be associated with a higher likelihood of a biologically low risk tumor. Half of all screen-detected low risk tumors had an index score above 0.6, indicating an ultralow risk of distant metastasis. The transition from analog to digital mammography resulted in a decrease in detection of ultralow risk tumors and an increase in the detection of high risk tumors. Screen-detected low risk biology tumors are frequent and comprehension may aid to minimize overtreatment.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-01.
Abstract P3-02-14: INTEGRATED PROGRAM FOR BREAST CANCER CONTROL: PARTIAL PRESENTATION OF THE RESULTS OBTAINED INTHE FIRST 24MONTHS OF OPERATION
Authors: Blanco EC , Borges MM , Pinotti M , Gennari MB , Ribeiro IM , Nascimento CCP , Santos LFG , Sahium RC 
Published: August 2014

Abstract
Introduction Breast cancer is a public health problem in Brazil. This is due to the difficulty of primary prevention (eliminating risk factors or to diagnose and treat precursor lesions), with a consequent increase in the incidence and mortality from this cancer. The current challenge arises from the lack of access to a few specialized centers, which in turn ar e not always qualified for diagnosis and prompt treatment.
Objective To develop a strategic plan aimed at two management priorities: resolubility diagnostic and fast treatment of women with clinical or secondary changes to mammographic screening.
Methodology The Oswaldo Cruz Alemão Hospital (OCAH) in partnership with the Ministry of Health of Brazil has developed and deployed in the region of the Mooca - City of St. Paul the Integrated Program for Breast Cancer Control (IPBCC), which begins in the primary prevention (health education and removal of factors risk), continues with the mammographic detection and early diagnosis, modern instrumental in a Center for Diagnostic Detection and Tracking (CDDT), and culminates in the surgical and radiotherapy, ad juvant chemotherapy and hormone therapy or not, according to a standardized protocol. The care is coordinated in single query by mastologists trained in resolving service, with the participation of radiologists, oncologists, social workers, psychologists, nutritionists and health educators.
Results From January 2010 to December 2011 were met 12266 women, mean age 58 years (range, 22–89) of which 100 were diagnosed with breast cancer and the proportion of carcinomas was of 8 per 1000. The detection rate mammography, ultrasound, and by both methods were: 0.30, 0.30 and 0.25, respectively. Forty-one percent of cancers corresponded to stages Tis N0M0 (3%) and T1N0M0 (38%) predominantly in women aged less than 50 years (38% of the sample). The average time between diagnosis and recorded start of surger y or chemotherapy was 42 days (range 19–68). As for quality of care, satisfaction was 99% (n = 12143).
Conclusions The experience in resolving service provided a significant increase in the number of initial cases showing detection ratesper image consistent with the age distribution of population. It is expected that the tracking time and quality of service, allow the prevalent cancers cease to be diagnosed, privileging the incidents. The median time to diagnosis and early treatment of patients with cancer was significantly lower the average of 120 days recorded in some public reference services.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-14.
Abstract P3-03-01: 3D mapping of total choline in human breast cancer using high-speed MR spectroscopic imaging at 3T: initial experience during neoadjuvant therapy
Authors: Posse S , Zhang T , Royce M , Dayao Z , Lopez S , Sillerud L , Casey L , Eberhardt S , Lomo L , Rajput A , Russell J , Lee S-j , Bolan P 
Published: August 2014

Abstract
OBJECTIVE: To assess the feasibility of quantitative high-speed MR spectroscopic imaging (MRSI) of total Choline (tCho) as an adjunct to dynamic-contrast enhanced MRI to improve lesion characterization and monitor treatment response in patients undergoing neoadjuvant chemotherapy (NAC).
METHODS: Twelve patients with infiltrating ductal carcinoma (Table 1) were studied using a clinical 3T MR scanner (Siemens, Erlangen, Germany) equipped with 8- and 16-channel breast array (Hologic Inc., Bedford, MA). Four patients were studied before NAC. Four patients were studied once during NAC. Two patients were studied before and within 2–7 days of treatment initiation. One of these patients participated in an additional scan after 5 months of treatment. Two additional patients were studied at 3 time points during NAC. Measurements were performed using PRESS prelocalized 3D Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) using TR/TE=2000ms/135ms, matrix size up to 32×16×8, voxel size = 1cc, and total acquisition time of 10 minutes (including water reference scan). Additional data were collected at TE 60 ms to enhance sensitivity for detecting tCho and J-coupled resonances. TE-averaging (8 steps, DTE: 2.5 ms) was employed to minimize gradient sideband artifacts. Quantification of tCho in reference to tissue water was performed using spectral fitting and relaxation correction.
RESULTS: Strongly elevated tCho with maximum concentration up to 5.3 mmol/kg was measured in 9 patients with enhancing lesions larger than 2 cc volume (Table 2). Decreases in tCho were measured in all four patients who were followed during neoadjuvant chemotherapy. Decreases in tCho were measurable during the first week of neoadjuvant treatment in responders, consistent with previous studies. Our preliminary data also indicate that the combination of concentration and spatial extent of detectable tCho may be the most sensitive marker of treatment response.

CONCLUSION: This study demonstrates feasibility of quantitatively mapping tCho in invasive breast carcinoma using high-speed MRSI. The long-term goals are to utilize high-speed MRSI as an early predictor of treatment failure in women undergoing neoadjuvant therapy (i.e. chemotherapy, endocrine therapy or biologic therapy) for breast cancer and to develop an improved screening protocol for high-risk patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-03-01.
Abstract P3-03-03: A tri-modality imaging assessment algorithm to evaluate neoadjuvant therapy response in patients with operable breast cancer
Authors: Umphrey H , Bernreuter W , Bland K , Carpenter J , Falkson C , Forero A , Keene K , Krontiras H , Meredith R , Urist M , De Los Santos J 
Published: August 2014

Abstract
Background: To determine the negative predictive value (NPV), positive predictive value (PPV), accuracy, sensitivity and specificity of a pre-surgical tri-modality imaging assessment algorithm to determine complete pathologic response (pCR) post neoadjuvant therapy in patients with operable breast cancer.
Methods: A retrospective analysis was performed on data collected from patients receiving neoadjuvant therapy and pre-surgical breast magnetic resonance imaging (MRI), ultrasound (US) and mammography between 2004 and 2010 at our institution. Tri-modality imaging was reviewed by a single blinded breast radiologist and evaluated for predetermined modality specific parameters as defined in Table 1. The NPV, PPV, accuracy, sensitivity, and specificity were calculated on the basis of the final surgical pathology report with a complete pathologic response in the breast defined as no residual invasive disease or in situ disease.
Results. Eighty-three tumors in 83 patients with a mean age of 50 (range 27–70) were evaluated. Twenty-three patients had a pCR. The NPV, PPV, sensitivity, specificity, and accuracy of tri-modality imaging algorithm for pCR were 0.87, 0.95, 0.95, 0.87 and 0.93 utilizing a cut-point of ≤ 5 for complete response by imaging. The mean score for patients with pCR was 4.61 (range 3–10) with 3 patients scoring above 5. The mean score for patients with residual disease was 7.73 (range 5–11).
Conclusions: A tri-modality imaging scoring algorithm is predictive of complete pathologic response. This algorithm will be tested in a developing prospective trial that will also assess the additive value of tumor bed biopsy in patients who achieve a score of 5 or less.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-03-03.
Abstract P3-04-01: Protein pathway activation mapping of the I-SPY 1 biopsy specimens identifies new network focused drug targets for patients with triple negative tumors
Authors: Wulfkuhle JD , Wolf D , Gallagher RI , Yau C , Calvert V , Espina V , Illi J , Wu Q , Boe M , Yan Y ,   I-SPY TRIAL-1 Investigators, Liotta LA , van't Veer L , Esserman L , Petricoin EF 
Published: August 2014

Abstract
Background: Identification of new therapies and predictive biomarkers is needed for patients with triple negative (TN) breast cancer. Elucidating pathway activation in cancer is critical as these proteins represent targets for many of the new molecular therapeutics and companion diagnostic markers. The I-SPY TRIAL (CALGB 150007/150012, ACRIN 6657) is a trial of neoadjuvant anthracycline- and taxane-based chemotherapy that provides longitudinal biopsy specimens and molecular and clinical/pathological characterization.
Methods: Tumor epithelium was procured by Laser Capture Microdissection from 149 pretreatment frozen biopsy specimens (T1) and 102 frozen biopsy specimens collected 1–4 days after first chemotherapy treatment (T2). Reverse Phase Protein Microarray was used to measure the activation of 39 and 100 signaling proteins in the T1 and T2 biopsies, respectively, including drug targets for Phase I-III and FDA cleared therapeutics. Associations between pathway activation and response to chemotherapy (RCB 0/1 vs. 2/3) and relapse-free survival (RFS) were evaluated for the triple-negative (TN) patient population at each time point and for changes between T1 and T2. Significance thresholds for response and RFS were as follows: Wilcoxon rank sum test p &lt; 0.05; Cox proportional hazard model, likelihood ratio p &lt; 0.05.
Results: We focused our analysis on protein changes in patients who had poor clinical outcomes (Table 1)

We observed systemic activation of receptor tyrosine kinases such as MET and ALK in the T2 biopsies from patients that recurred, and VEGFR activation was seen in the T1 relapsed tumors. Activation in the AURORA-PLK1 cell cycle signaling network was seen with increased activation in the T2 biopsy from patients who did not respond to therapy and had poor RFS. Dynamic changes in ERK activation were revealed with decreased ERK activation between T1 and T2 time points associated with recurrence.
Conclusions: Our analysis has revealed activation and increased expression of proteins involved in proliferation (Ki67), DNA repair (phosphorylated p53) and protein kinases in patients with TN disease who had poor clinical response. These events, if validated, point to potential treatment options that could be considered for non-responding TN breast cancer patients. VEGFR, ALK and MET, have FDA cleared therapeutics that could be rationally proposed for rapid clinical investigation, and there are numerous investigational agents that target AURORA and PLK1 in the clinic. Further validation is required to explore the significance of these ongoing findings with the hope that the analysis could lead to molecularly rationalized therapies for patients with TN tumors.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-04-01.
Abstract P3-04-05: Kinomic and phospho-proteomic analysis of breast cancer stem-like cells
Authors: Leth-Larsen R , Christensen AG , Ehmsen S , Moeller M , Palmisano G , Larsen MR , Ditzel HJ 
Published: August 2014

Abstract
Cancer stem cells are thought to be responsible for tumorigenic potential and to possess resistance mechanisms against chemotherapy- and radiation-induced cancer cell death, while the bulk of a tumor lacks these capacities. The resistance mechanisms may cause these cells to survive and become the source of later tumor recurrence, highlighting the need for therapeutic strategies that specifically target pathways central to these cancer stem cells. The CD44hi/CD24−/low compartment of human breast cancer is enriched in tumor-initiating cells; however the functional heterogeneity within this subpopulation remains poorly defined.
From a triple-negative breast cancer cell line we isolated and cloned CD44hi single-cells that exhibited functional heterogeneity according to cancer stem cell features, such as tumor formation in immunodeficient mice, mammosphere formation, invasion and migration abilities and sensitivity to chemotherapeutics.
Quantitative proteomic analysis of these clones revealed several proteins, including kinases, exhibiting altered expression levels, while other proteins exhibited altered phosphorylation levels. The quantitative proteomic approach was based on post digestion dimethyl labeling followed by TiO2 enrichment of phosphopeptides. Moreover, analysis of the flowthrough fraction revealed quantitative changes in the total proteome. Transcriptomic analysis using Affymetrix Human Gene 1.0 ST Arrays revealed similar alterations at the gene expression level.
We used these single cell clones to further investigate the molecular mechanisms underlying the association between selected proteins, some of them phosphorylated, and cancer stem cell features. Furthermore, phosphosite-expression was investigated with NetworKIN that predicts in vivo kinase-substrate relationships.
Our studies reveal pathways that are regulated by protein phosphorylation and include relevant kinase targets for drug discovery. Our results support functional heterogeneity in the breast cancer cell compartment and hold promise for further refinements of prognostic marker profiling of cells with cancer stem cell-like features.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-04-05.
Abstract P3-04-08: Expression of hormone-responsive genes in benign breast tissue varies with menstrual cycle phase and menopausal status
Authors: Hu H , Wang J , Lee O , Shidfar A , Iyer S , Ivancic D , Chatterton RT , Stearns V , Sukumar S , Khan SA 
Published: August 2014

Abstract
Background: The expression of many genes is known to be regulated by ambient hormone levels. In a preliminary study of random fine-needle aspirate (rFNA) samples from benign breast tissue, we found several genes that were highly correlated with the serum levels of progesterone (P4) and estradiol (E2). We now present data to further validate these genes as markers of menstrual cycle phase (MCP) and menopausal status (MPS) in benign breast tissue which may allow retrospective classification of archived breast samples with respect to MCP and MPS at the time of sampling.
Methods: 240 rFNA samples from healthy women with recorded hormonal data at the time of sampling were analyzed. We divided these subjects by menstrual cycle phase (MCP) and menopausal status (MPS): 41 early follicular: (low circulating E2 and P4); 48 mid-cycle (high E2 and low P4); 31 luteal (moderate E2 and high P4). 120 post-menopausal (low E2 and low P4). 100 ng of RNA from rFNA samples of the breast was reverse transcribed. Amplicons of interest were linearly amplified to 14 cycles for 35 genes related to hormone responsiveness. qPCR reactions were carried out using the TaqMan OpenArray (Applied Biosystems). For each gene of interest, expression levels were normalized to the average expression of GAPDH. Gene expression difference between groups were conducted using the Mann-Whitney Test. P-values from gene expression difference were adjusted via the Benjamini-Hochberg (1995) approach.
Results: The mean value of TNFSF11 expression level was 13.19 fold higher in luteal phase subjects than in post-menopausal subjects (p = 0.0003) where there was also the biggest difference of serum P4 level between groups. The expression of DIO2 and MYBPC1 was also significantly higher in luteal phase group than in the post-menopausal group (p = 0.005, p = 0.02, respectively). These 3 genes also demonstrated a higher expression pattern in luteal phase than mid-cycle and follicular phase but analysis is still ongoing. All comparisons between these groups will be presented at the meeting.
Conclusion: The expression levels of TNFSF11, DIO2 and MYBPC1 vary with MCP and MPS. These hormone-responsive genes are candidate MCP classifiers which could be applied to archived breast samples to assess whether biomarkers of breast cancer risk are stable across the menstrual cycle, since MCP and MPS variation is likely an important source of biological noise in studies of archived breast biopsy material.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-04-08.
Abstract P3-04-12: BreastMark: An integrated approach to mining publically available Transcriptomic Datasets relating to Breast Cancer Outcome
Authors: Madden S , Gaule P , Clarke C , Aherne ST , O'Donovan N , Clynes M , Crown J , Gallagher WM 
Published: August 2014

Abstract
Background: Breast cancer is a complex heterogeneous disease for which a substantial resource of transcriptomic data is available. Indeed, gene expression data have facilitated the division of breast cancer into, at least, five molecular subtypes, Luminal A, Luminal B, Her2, Normal-like and Basal. Once identified, breast cancer subtypes can inform clinical decisions surrounding patient treatment and prognosis. It is important to identify patients at risk of developing aggressive disease so as to tailor the level of clinical intervention.
Methods: We have developed a user-friendly web-based system to allow the identification and evaluation of genes that are significantly associated with disease progression and survival for breast cancer in general and also with respect to molecular subtype. The underlying algorithm combines gene expression data from multiple DNA microarray experiments and detailed clinical data to correlate outcome with gene expression levels. This algorithm integrates gene expression and survival data from 21 datasets on 10 different microarray platforms corresponding to 20,017 gene sequences across 3,519 samples.
Results: We demonstrate the robustness of our approach in comparison to two commercially available prognostic tests in breast cancer. Our algorithm complements these prognostic tests and is consistent with their findings. In addition, BreastMark can act as a powerful reductionist approach to these more complex gene signatures, eliminating superfluous genes, potentially reducing the complexity and cost of these multi-index assays. We also applied the algorithm to examine expression of 58 receptor tyrosine kinases in the basal-like subtype of breast cancer, identifying seven receptor tyrosine kinases associated with poor disease-free survival and/or overall survival in this subtype (EPHA5, FGFR1, FGFR3, VEGFR1, PDGFRβ, ROS, TIE1). A web application for using this algorithm is currently available at http://glados.ucd.ie/BreastMark/index.html.
Conclusions: BreastMark is a useful tool for examining putative prognostic markers at the RNA level in breast cancer. The value of this tool will be in the preliminary assessment of putative biomarkers in breast cancer as a whole and within its molecular subtypes. It will be of particular use to clinical and academic research groups with limited bioinformatics facilities.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-04-12.