bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-01-21: Sentinel Lymph Node detection after previous breast tumour surgical resection: identification rate and false negative rate through a prospective multi institutional study.
Authors: Classe J-M , Andrieux N , de Lara Tunon C , Charitansky H , Lecuru F , Houpeau J-L , Faure C , De Blaye P , Houvenaeghel G , Kere D , Marchal F , Raro P , Lefebvre C , Dupré P-F , Rodier J-F 
Published: August 2014

Abstract
Background: Large multi institutional studies have pointed that previous surgical resection of breast tumours before axillary sentinel node detection (ASLND) was the main criteria of failure of this technique. Screening campaigns provide small tumours and despite efforts to obtain a diagnosis of early breast cancer, this is not always obtained, due to small tumours or false negative results of micro biopsies. The aim of our series was to assess identification rates and false negative rates of ASLND after previous surgical resection of breast tumours.
Material and Methods: In a prospective multi institutional setting (14 multidisciplinary teams), we have included patients with a previous breast tumour surgical resection for the diagnosis of infiltrative breast adenocarcinoma. Patients with only a core biopsy and no surgical removal of the tumor before axillary surgery were not included. Each patient underwent a secondary surgical procedure for ASLND and axillary lymphadenectomy, and sometimes a breast secondary surgical procedure for margins. ASLND was performed with the combined method, with blue dye and technetium. Pathology was performed with serial sectioning, eosin safron and immune histo chemistry (IHC).
Results: From July 2006 to November 2011, 138 patients where included. The median tumor size was 9mm. Identification rate was 86% (118/138). A macrometastasis was found in 11 cases, in a sentinel node (9), or in a non sentinel node(2). False negative rate was 9% (1 false negative sentinel node with macrometastasis in non sentinel node from lymphadenectomy/11 cases with a macrometastasis in either a sentinel node or a non sentinel node). In 1 case a micrometastasis was found in a sentinel node through IHC, with a macrometastasis in a non sentinel node from lymphadenectomy. Without IHC or without the decision of performing a complementary lymphadenectomy in the case of micrometastasis, the false negative rate would have been 18%.
Conclusions: After previous surgical resection of early breast cancer, ASLND remains feasible with a low identification rate of 86%, despite the use of the combined method. The False negative rate is acceptable with the use of IHC.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-01-21.
Abstract P1-04-06: Insertional mutagenesis identifies HACE1 as a HER2/Neu Cooperating Breast Cancer Tumor Suppressor Gene
Authors: Goka E , Miller P , Baker K , Stark G , Lippman ME 
Published: August 2014

Abstract
The development of human breast cancer is a multi-step process leading from normal epithelium to fully transformed breast cancer. Early genetic changes result in hyperplasias which evolves into ductal carcinoma in situ (DCIS) and culminates as invasive ductal carcinoma. The transition from DCIS to invasive disease has been implicated as the key transition in breast cancer progression. Specific genomic, transcriptomic, and proteomic alterations responsible for this transition process have yet to been elucidated.
HER2/Neu, a member of the EGFR family of receptor tyrosine kinases, is associated with poor clinical outcome. HER2/Neu overexpression/amplification is commonly seen (50–60%) in non-invasive lesions but is significantly less common (20–30%) in invasive and metastatic breast carcinoma. This indicates that HER2/Neu gives normal epithelium a proliferative advantage but additional genetic alterations are required for full malignant transformation. This idea is supported by the fact that transgenic mice that overexpress HER2/Neu develop spontaneous mammary tumors but only after a prolonged latency period.
Recent forward genetic approaches use insertional mutagenesis to randomly integrate a strong promoter into the genome, activating downstream gene transcription that can lead to either gain or loss-of-function mutations based on the integration site. We used this insertional mutagenesis approach to induce anchorage-independent growth of isolated murine HER2/Neu over-expressing mammary epithelial cells. We identified HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) as a putative breast tumor suppressor protein whose loss leads to the formation of anchorage-independent colonies.
Loss of HACE1 expression is commonly seen in breast cancer patients [as well as other tumor types] supporting the role of HACE1 as a breast tumor suppressor gene. Knockdown of HACE1 in human mammary epithelial cells (HMECs) results in the acquisition of anchorage-independent growth. Moreover, knockdown of HACE1 in established breast cancer cell lines that express moderate levels of HACE1 results in enhanced cloniginicity.
Therefore, we propose that the loss of HACE1 can potentially be used as a predictive marker for breast cancer progression. Additional studies investigating the mechanism of HACE1 action may also identify therapeutic targets that counteract HACE1 loss.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-04-06.
Abstract P1-04-07: The mRNA Expression of DAP1 in Human Breast Cancer: Correlation with Clinicopathological Parameters
Authors: Wazir U , Jiang WG , Sharma AK , Mokbel K 
Published: August 2014

Abstract
BACKGROUND: This pilot study is the first to focus on the potential role for death-associated protein 1 (DAP1) in human breast cancer.
MATERIAL AND METHODS: mRNA expression of DAP1 in breast cancer tissues (n = 127) and normal background tissues (n = 33) were determined using quantitative polymerase chain reaction (qPCR) and correlated with clinicopathological data accumulated over a 10-year follow-up period. Furthermore the effects of DAP1 knockout in breast cancer cell lines were investigated.
RESULTS: The expression of DAP1 mRNA was demonstrated to decrease with increasing Nottingham Prognostic Index (NPI2 vs. NPI3, p = 0.0026), and TNM stage (TNM1 vs. 4, p = 0.0039). Lower DAP1 expression levels were significantly associated with local recurrence (p = 0.02) and distant metastasis (p = 0.001).
The knockout of the DAP1 gene in MCF-7 cell lines resulted in a significant decrease in the mRNA expression of P-21 and DELE compared with controls, p = 0.04). However, the knockout of DAP1 had no effect on the expression of caspase 8 and 9.
CONCLUSIONS: This study demonstrates an inverse association between DAP1 mRNA levels and tumour stage and clinical outcome in breast cancer. This may be suggestive of a relationship between oncogenesis and the autophagy pathway meriting further investigation. These results also indicate that the pro-apoptotic function seems to be estrogen-dependent but independent of caspase 8 and 9. The DAP1 pro-apoptotic pathway may involve P-21 and DELE proteins.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-04-07.
Abstract P1-04-09: mTORC1 and Rictor expression in human breast cancer: correlations with clinicopathological parameters and disease outcome
Authors: Wazir U , Kasem A , Sharma AK , Jiang WG , Mokbel K 
Published: August 2014

Abstract
BACKGROUND: mTOR (the mammalian target of rapamycin) plays a key role in regulation of cellular metabolism, growth, and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2 respectively. There is a growing body of evidence that mTORC1 is up-regulated in many cancers and plays a role in carcinogenesis. The aim of the study was to investigate the mRNA expression of mTOR and Rictor in human breast cancer and examine the relationship between their expression and clinicopathological parameters.
METHODS: Specimens of breast cancer (BC) tissues (N = 150) and normal tissues (N = 31) underwent RNA extraction and reverse transcription. mTOR and Rictor transcript levels were determined using real-time quantitative PCR. Expression levels were analyzed against tumor size, grade, nodal involvement, TNM stage, and clinical outcome over a 10 year follow-up period.
RESULTS: Significantly higher mRNA transcript levels of mTOR were found in the breast cancer specimens compared to normal glandular tissue (p = 0.0018). The expression of mTOR mRNA was demonstrated to increase with increasing NPI (53 for NPI1 to 219 for NPI3) and tumor grade (37 for grade 2 vs. 159 for grade 3, p = 0.047). mTOR expression was found to be higher in ductal tumors compared with non-ductal tumors (p = 0.0014). The patients who developed recurrent disease or died from breast cancer had higher expression levels than those who had been disease-free after a median follow-up period of 10 years (p = 0.17). Higher expression levels were significantly associated with worse overall survival (p = 0.01).
In contrast, higher levels of Rictor mRNA expression were found in normal breast tissue, lower NPI stage (NPI1 vs. 2: p = 0.03) and lower tumor grade (grade 1 vs. grade 3: p = 0.01). Patients with higher Rictor expression had a significantly better overall (p = 0.037) and disease-free (p = 0.048) survival.
CONCLUSIONS: mTOR expression was found to be significantly higher in BC specimens compared to normal breast tissue. Higher transcript levels were significantly associated with unfavorable pathological parameters and adverse clinical outcomes. The core protein of the less predominant mTORC2 was associated with favorable pathological parameters and clinical outcome. Taken together these observations are consistent with mTORC1 role in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 are likely to be a more effective therapeutic strategy than dual inhibitors in human breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-04-09.
Abstract P1-07-04: Comparison of HER2 expression by immunohistochemistry (IHC) using automated imaging system and fluorescence in situ hybridization (FISH). A retrospective analysis of 2853 cases
Authors: Collins R , Xiang D , Christie A , Leitch M , Euhus D , Rao R , Haley B , Sarode V 
Published: August 2014

Abstract
Background: Accurate assessment of HER2 status is critical for selecting patients who will benefit from trastuzumab therapy. There is still no consensus regarding the optimal method to assess HER2 status. Computerized image analysis has been shown to provide a more accurate and objective way for quantification of HER2 expression by IHC than manual evaluation. It has been suggested that the use of image analysis may help to resolve some of the discrepancies between IHC and FISH assay.
We compared the results of HER2 expression by IHC using automated image analysis with fluorescent in situ hybridization (FISH) assay.
Design: Testing for HER2 expression by IHC and FISH was performed on 2853 specimens at UT Southwestern Medical Center between the years 2002 to 2011. Quantification of IHC HER2 expression was done by image analysis and scored as positive (&gt;2.0), borderline (1.5 to 2.0) and negative. (&lt;1.5). The PathVysion kit was used for FISH assay to evaluate HER2 amplification. Ratios &gt;2.0, 1.8 to 2.0 and &lt;1.8 were defined positive, borderline and negative amplification respectively.
Results: IHC compared to FISH

Conclusion: Despite improvements in IHC testing, the FISH assay may be a better method for determining HER2 status. Factors such as tissue fixation, scoring methods and choice of antibodies may contribute to the lower specificity of IHC.
In the amplified group, the gene amplification ratio correlated with protein expression, being highest in the IHC positive cases and lowest in those that were negative.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-04.
Abstract P1-07-14: Enabling biomarker validation in breast cancer molecular subtypes: sensitivity and specificity of array-based subtype classification in 983 patients
Authors: Györffy B , Lanczky A 
Published: August 2014

Abstract
Background: The diverse breast cancer molecular subtypes have different clinicopathological characteristics and outcomes. Here, we assessed the correlation between microarray-defined and author-reported molecular subtypes using publicly available breast cancer datasets.
Methods: GEO was searched for datasets where the authors determined molecular subtypes. The molecular subtype was re-calculated for each patient using the StGallen guidelines by assessing the microarray-based expression of ER, HER2 and MKI67 (Basal: ER negative + HER2 negative, Luminal A: ER positive + HER2 negative + low MKI67, HER2 enriched: HER2 positive + ER negative, Luminal B: ER positive + HER2 positive and ER positive + HER2 negative + high MKI67). The thresholds used were 500 for ER (probe set 205225_at), 4800 for HER2 (216836_s_at) and 470 for MKI67 (212021_s_at). Sensitivity and specificity were calculated for each subtype separately.
Results: Molecular subtype was published in all together six datasets (GSE1456, GSE21653, GSE25066, GSE20711, GSE31519 and GSE17907) for 983 patients. In these, 380, 306, 169 and 128 were Basal, Luminal A, Luminal B and HER2 enriched, respectively. The microarray-based molecular subtype determination resulted in a sensitivity of 0.70, 0.55, 0.63 and 0.38 and a specificity of 0.96, 0.87, 0.67 and 0.99 for Basal, Luminal A, Luminal B and HER2 enriched subtypes, respectively. Finally, the option to filter for molecular subtypes was implemented into our online biomarker validation platform at www.kmplot.com.
Discussion. Microarray data provided highest sensitivity and specificity to independent subtype classification for Basal tumors, while the luminal B subtype displayed the highest discordance. Our registration-free online service enables the validation of gene expression based biomarkers in each subtype separately.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-14.
Abstract P1-10-01: Curcumin suppresses MMP-9 expression via inhibition of PKCα/MAPKs and NF-κB/AP-1 activation in MCF-7 cells
Authors: Kim SK , Kim YW , Youn HJ , Jung SH 
Published: August 2014

Abstract
Background: Curcumin is a polyphenol derived from the plant turmeric (Curcuma longa), which is commonly used as a spice. It was recently reported for its anticancer effect on several types of cancer cells in vitro, however the molecular mechanisms of this anticancer effect are not fully understood. In the present study, we investigated the effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced matrix metalloproteinase-9(MMP-9) expression and cell invasion in MCF-7 breast cancer cells.
Materials and Methods: The effect of curcumin on MCF-7 cell viability was determined using MTT assay. The cells invasion was demonstrated by the Matrigel-coated transwell assay. Western blot analysis was performed to detect the effect of curcumin on the expression of MMP-9. MMP-9 mRNA levels were analyzed by real-time PCR. NF-κB and AP-1 DNA binding was analyzed by EMSA.
Results: Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation. Curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK and also inhibited TPA-induced translocation of PKCa from the cytosol to the membrane, but did not affect the translocation of PKCδ.
Conclusion: It is concluded that curcumin inhibits the TPA-induced MMP-9 expression and cell invasion through the suppression of the PKCα/MAPK/NF-kB/AP-1 pathway in MCF-7 breast cancer cells. Accordingly, curcumin may have the therapeutic potential in restricting breast cancer metastasis.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-10-01.
Abstract P1-13-06: Breast cancer survival advantage with oral bisphosphonates use
Authors: Rennert Gad , Rennert Hedy S , Pinchev Mila , Landsman Keren , Lejbkowicz Flavio 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-06.
Abstract P1-14-09: Immunohistochemical classification of intrinsic subtypes as a predictive biomarker of pathological compelete response in breast cancer patients treated with preoperative chemotherapy.
Authors: Nagayama A , Jinno H , Takahashi M , Hayashida T , Hirose S , Kitagawa Y 
Published: August 2014

Abstract
Background: Analysis of gene expression arrays has resulted in the recognition of several fundamentally different subtypes of breast cancer. These subtypes have different natural histories and different responses to systemic and local therapies. However, widespread use of gene expression profiling is limited because of its expense and of technical difficulty. Alternatively, this classification has also been reproduced in immunohistochemical studies. The objective of this study was to evaluate the clinical utility of immunohistochemical classification of breast cancer intrinsic subtypes in the prediction of pathological compelete response (pCR) in a cohort of breast cancer patients receiving the sequential combination of taxane followed by anthracycline as preoperative chemotherapy.
Materials and methods: A prospective database of 150 women with stage II/ III breast cancer, who received neoadjuvant chemotherapy, was analyzed. The regimens were either four cycles of docetaxel (40 mg/m2 on day 1 every 3 weeks) with S-1 (80 mg/m2 on days 1–14 every 3 weeks) followed by four cycles of 5-fluorouracil (500 mg/m2), epirubicin (100 mg/m2) and cyclophosphamide (500 mg/m2) (FEC) or four cycles of docetaxel (60 mg/m2 on day 8 every 3 weeks) with capecitabine (1650 mg/m2 on days 1–14 every 3 weeks) followed by four cycles of FEC. Subtypes were classified into luminal A (lumA) (ER+ and/or PgR+, HER2−, Ki67&lt;14%), luminal B (lumB) (ER+ and/or PgR+, HER2−, Ki67&gt;14%), triple-positive (TP) (ER+ and/or PgR+, HER2+), HER2 (ER−, PgR−, HER2+), and triple-negative (TN) (ER−, PgR−, HER2−) by using immunohistochemically stained specimen obtained by core needle biopsy. Absence of invasive tumor cells in the breast at the time of surgery was defined as pCR.
Results: We found 34 women in lumA, 54 in lumB, 15 in TP, 8 in HER2, 33 in TN. The median age in each group was 53, 51, 50, 57 and 53 respectively (p = .397). The mean tumor size was 3.2cm, 3.5cm, 4.4cm, 3.9cm and 3.6cm respectively (p = .158). The clinical response rate measured by physical examination (calliper) was 80.6%, 93.9%, 86.7%, 100% and 82.4% (p = .378). pCR rate was 5.9%, 14.8%. 13.3%, 50%, 21.2% respectively (p = .031). The multivariate analysis showed ER negative, PgR negative and intrinsic subtype (TN) were the significant predictive factors of pCR (p = .027, p = .003, p = .004).
Conclusion: This study indicated that immunohistochemical classification of intrinsic subtype might be a useful predictive biomarker of pCR in breast cancer patients treated with preoperative chemotherapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-09.
Abstract P1-15-10: Chemotherapy-Induced Neutropenia in Breast Cancer Patients Receiving Sequential Anthracycline and Taxane Chemotherapy: An institutional experience
Authors: Staudigl C , Seifert M , Tea M-K , Pfeiler G , Fink-Retter A , Fritzer N , Singer CF 
Published: August 2014

Abstract
Background: Sequential regimen of anthracyclines and taxanes are commonly used in patients with early stage breast cancer (BC) and curative treatment intent. Due to the associated myelotoxicity, internationally accepted guidelines recommend granulocyte-colony stimulating factors (G-CSF) as primary or secondary prophylaxis, dependent on chemotherapy (CT) and patient-associated risk of febrile neutropenia. As part of a quality control initiative at our center, we have analyzed rates of grade 1 or 2 (&lt;2.0 to &gt;1.0 × 109/L) and 3 or 4 (&lt;1.0 to &lt;0.5 × 109/L) neutropenia, febrile neutropenia (&lt;0.5 × 109/L and single oral temperature ≥38.3°C/100.4°F), CT dose reductions, anti-infective use, and hospitalizations in cycles with pegfilgrastim prophylaxis.
Methods: Patients (pts) with BC stages I to III received four three-weekly (q21) cycles of adjuvant or neoadjuvant EC (Epirubicin 90 mg/m2 + Cyclophosphamide 600 mg/m2 q21) followed by four cycles of D (Docetaxel 100 mg/m2 q21) plus primary or secondary pegfilgrastim prophylaxis. Chart records were collected and analyzed retrospectively for patients treated between 2009 and 2012 at our institution for incidence of neutropenia and for the presence of neutropenia-associated risk factors. Only cycles with pegfilgrastim prophylaxis were considered for this analysis.
Results: 100 consecutive patients were identified who had overall received 200 EC cycles followed by 251 D cycles under G-CSF prophylaxis with pegfilgrastim. Pts age mean: 51,57 (SD:11,23), BMI mean: 25,8 (SD:5,03) were well controlled in both sequences. Overall, neutropenia was significantly higher for EC (p = 0.001), however higher grade neutropenia (Grade3 and 4) were comparable (p = 0.200). No statistically significant correlations were found between neutropenia and age or body mass index.

Conclusions: Sequential use of EC followed by D in combination with prophylactic pegfilgrastim results in lower den expected FN rate [1]. In contrast to most published trials EC leads to significantly more neutropenias than D. However, the use of pegfilgrastim reduces both EC and D associated neutropenias grade 3 and 4 to a similar extent.
References:
1. Aapro, M.S., et al., 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 47(1): p. 8–32.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-10.
Abstract P2-04-02: Identification of genes associated with breast cancer micrometastatic disease in bone marrow using a human-in-mouse xenograft system
Authors: Aft R , Li S , Mudalagiriyappa C , Dasgupta N , Watson M , Fleming T , Ellis M , Pillai S 
Published: August 2014

Abstract
Disseminated tumor cells (DTCs) found in the bone marrow (BM) of breast cancer patients portend a poor prognosis and are thought to be the intermediaries in the metastatic process. Study of these cells has been limited due to their scarcity. To develop a clinically relevant model to characterize hese cells, we have employed a human in mouse (HIM) xenograft model for propagating, isolating, and molecularly characterizing DTCs. Human breast adenocarcinomas were prospectively collected from 5 patients and implanted into humanized NOD/SCID mouse mammary fat pads. BM was collected from the long bones at varying passages of the tumors and analyzed for human-specific gene expression by qRT-PCR and gene expression microarray. Human-specific gene expression of SNAI1, GSC, FOXC2, KRT19, and STAM2, presumably originating from disseminated tumor cells, was detectable in the BM of all mice that had developed metastatic disease to other solid organs, but was not detectable in xenotransplanted mice that did not develop metastatic disease. Comparative gene expression microarray analysis of the HIM primary tumor, the corresponding BM from mice with metastatic disease, and BM from control mice identified additional patterns of gene expression enriched in BM-associated DTCs which included several genes associated with epithelial-mesenchymal transition, aggressive clinical phenotype, and metastatic disease development in primary human tumors. We have found that BM DTCs can be detected using the HIM xenograft model and have identified unique patterns of gene expression associated with BM DTCs, which may provide further insight into the biology and therapeutic vulnerability of metastatic tumor cell populations in breast cancer patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-04-02.