bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of preoperative letrozole treatment to DCIS by MRMammography.
Authors: Kuwayama T , Nakamura S , Yoshida A , Yagata H , Tsugawa K , Takei J , Tsunoda-Shimizu H , Suzuki K 
Published: December 2010

Abstract
Abstract #1164
Background:&#x2028; Since ductal carcinoma in situ (DCIS) often spreads diffusely along a lactiferous duct as multicentric lesions, it is generally treated by mastectomy. The response rate to letrozole is approximately 60%, which is relatively high among the preoperative endocrine therapies for invasive cancer, and it enables at least 50% of patients with little chance of saving the breast to actually receive breast-conserving surgery. This study was conducted to determine the value of preoperative endocrine therapy with letrozole for postmenopausal patients with hormone receptor (HR)-positive DCIS.&#x2028; Methods:&#x2028; Postmenopausal women who had been diagnosed with HR-positive DCIS by needle biopsy (Allred score ≥3) were treated with letrozole for 12 weeks. The primary endpoint was the response of target lesions evaluated by MRI based on the RECIST criteria. Patients who had no safety problems, except PD, continued letrozole therapy for up to 24 weeks, and the tumor response after 24 weeks and the rate of breast-conserving surgery were assessed. In addition to RECIST-based evaluation, changes of tumor volume on MRI were examined. Changes of Ki67, bcl-2, ER, and PgR with letrozole therapy were also assessed.&#x2028; Results:&#x2028; Twelve postmenopausal women with DCIS were enrolled, but one patient was excluded because her Allred score was 2. Using by RECIST criteria , the tumor response after 12 weeks was CR in 1 patient and SD in 10 patients. All 6 patients who could be evaluated after 24 weeks showed SD. But the evaluation by tumor volumetoric method, tumor was significantly reduced to an average of 42.2% after 12 weeks compared to before treatment.(p=0.0057) Two patients continued letrozole therapy for longer than 24 weeks. After 24 weeks of therapy, 3 patients underwent breast-conserving surgery and no mastectomies were performed. Pathological findings showed that the spread of tumor was likely to that of preoperative MRMammogrraphy. PgR was significantly reduced by letrozole therapy. There were no safety problems was not observed.&#x2028; Discussion:&#x2028; The efficacy of preoperative treatment with letrozole for 12 weeks was verified in postmenopausal patients with HR-positive DCIS. Two patients received breast-conserving surgery after letrozole therapy that had been considered impossible before treatment. Evaluation of treatment to DCIS using by RECIST criteria is unsutable,but the evaluation by MRMammography is considered to be a suitable method for determining the efficacy of therapy for DCIS.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1164.
Using mathematical models to understand the time dependence of the growth of ductal carcinoma in situ.
Authors: Edgerton ME , Chuang Y , Macklin PT , Sanga S , Kim J , Tamaiuolo G , Yang W , Broom A , Do K , Cristini V 
Published: December 2010

Abstract
Abstract #1165
Background: Models of cancer growth have been developed that predict tumor size and growth dynamics for invasive tumors. However, it has been difficult to model ductal carcinoma in situ (DCIS) because of the constraints introduced by its containment within the duct system.&#x2028; Materials and Methods: We have developed a spherical model of growth of solid type DCIS using chemical engineering models of reaction and diffusion in porous media to represent the spread of DCIS in the duct systems. The model predicts tumor diameter based on four input parameters: the ratio of the apoptosis rate to the proliferation rate (A), the diffusion penetration length for nutrient to sustain the tumor growth (L), the volume fraction that tumor cells occupied within the involved breast tissue (V), and the time taken for a cell to complete mitosis(T). We have estimated L, V, and T from the literature, and then back-calcuated A for a range of diameters. We have used these four parameters as inputs and studied the time dependence of the evolution of DCIS.&#x2028; Results: We have found that the range of the values of A that we determined are within an adeqaute physiological range based on rates of proliferation and apoptosis taken from the literature. Using the model, the time to reach at least 95% of the maximum size ranges from less than 30 days for DCIS measuring 0.5 cm to almost 80 days for DCIS measuring 6 cm in diameter.&#x2028; &#x2028; Discussion: There has been little understanding of how long it takes for DCIS to grow, and whether it reaches a steady state size. Our simulations show that DCIS can grow to sizes as large as 6 cm in less than 3 months if it has the correct properties, including a high proliferation rate relative to the apoptosis rate and appropriate access to nutrients. This finding may help to explain why many cases of DCIS are not diagnosed before they progress to invasive carcinoma.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1165.
CA 27.29 as a tumour marker for risk evaluation and therapy monitoring in patients with primary breast cancer.
Authors: Hepp PG , Rack BK , Mouarrawy D , Groh U , Graf H , Göhler T , Finas D , Hönig A , Lichtenegger W , Sommer H , Janni W 
Published: December 2010

Abstract
Abstract #2004
Background:&#x2028; Several trials show that the use of tumor markers leads to an early diagnosis of tumor dissemination in breast cancer patients. Whether this improves the prognosis is still under discussion. In the SUCCESS Trial CA27.29 has been examined before and after adjuvant chemotherapy (n=3754).&#x2028; Methods:&#x2028; The SUCCESS Trial compares FEC-Docetaxel (Doc) vs. FEC-Doc-Gemcitabine (Doc-G) regime and two vs. five year treatment with Zoledronat in patients with primary breast cancer (N+ or high risk). CA27.29 has been measured with ST AIA-PACK Ca27.29 reagent using MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). The cutoff for positivity of CA27.29 is 24 U/ml.&#x2028; Results:&#x2028; 2669 patients have been examined prospectively before and after chemotherapy. 22% of patients had a marker &gt;24 U/ml (n=587, mean 19.00, range 3.04-410.00) before and 40% (n=1058, mean 23.34, range 2.70-330.76) after chemotherapy. The correlation between both values was significant (p&lt;0.0005).&#x2028; While 17% showed elevated CA27.29 before and after therapy, 5% patients changed from positive to negative for CA27.29 afterwards. 55% were negative before and after therapy whereas 23% became positive after treatment.&#x2028; &#x2028; Before treatment the prevalence of elevated CA27.29 was equally distributed between the FEC-Doc and the FEC-Doc-G arm. After treatment 34.1% in the FEC-Doc arm showed an increased level vs. 45.6% in the FEC-Doc-G arm. The correlation analysis showed no significant coherence between hormonal status (ER: p&lt;0.323; PR: p&lt;0.078), HER2/neu status (p&lt;0.308), Grading (p&lt;0.565) and CA27.29 level. However, tumor size (p&lt;0.020) and the nodal status (p&lt;0.022) were significant associated with Ca27.29 levels.&#x2028; Conclusion:&#x2028; These results might indicate a close relation between Ca27.29 and tumour mass at primary diagnosis. Whether this marker will be useful for treatment monitoring will be shown by further follow-up in the Success-trial.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2004.
HoxC6 regulation of early mammary epithelial growth and differentiation: implications for breast cancer potential.
Authors: Zhang G , Neumann CA , Moreno CS , Rosenzweig SA , Spyropoulos DD 
Published: December 2010

Abstract
Abstract #2010
Background: Early menarche and breast development are increasingly common risk factors for breast cancer. Epigenetic mechanisms implicated include natural and anthropogenic steroids, such as estrogens, that disrupt endocrine signaling and dysregulate stem cell homeostasis. Animal models show that, although a proliferative response to estrogens in mammary epithelium is not observed until near puberty, in utero or neonatal exposure can recapitulate aberrant breast development. The molecular basis for the delay in proliferative response remains poorly understood and assessments of agent activity, potency and risk remain inaccurate. Here, we provide a candidate molecular mechanism involving the homeobox transcription factor HoxC6, through which more accurate assessments may be facilitated.&#x2028; Materials & Methods: Genetically and hormonally manipulated in vivo mouse models (HoxC6 targeted disruption, C6KO; and mammary epithelial-specific inducible HoxC6, MMTV-rtTA TRE-HoxC6-IRES-EGFP) and in vitro human breast cancer cell lines (MCF10A, MCF7 and MDA-MB-231; "231") were used to assess impacts on mammary epithelial growth, differentiation and expression of HoxC6 and its direct target genes IGFBP3, CD44 and FGFR2. Cell lines were manipulated using HoxC6 shRNA and cDNA lentivirus and activated Akt isoform retroviral expression vectors. Gene expression and signaling were measured by quantitative RT-qPCR, IHC, Western blot and using the BioPlex200 Multiplex System.&#x2028; Results: RT-qPCR analysis shows HoxC6 expression elevated in well-differentiated cell lines (MCF10A, 5.06X; MCF7, 5.16X) and decreased in more aggressive tumor cell lines (-1.95X, 231 cells; relative to A549 cells). HoxC6 knockdown in MCF10A cells results in an inhibition of cellular growth and decreased branching in 3D cultures and dysregulation of HoxC6 target genes. These results are consistent with in vivo results in which C6KO causes defective postnatal mammary epithelial growth/branching. Rescue of growth defects in knockdown MCF10A cells is achieved to varying extents with myristoylated Akt isoforms, however morphological defects persist and are associated with EMT. HoxC6 induction in stem cells is associated with altered self-renewal and differentiation. HoxC6 repression by estrogens was assessed in vivo under conditions of neonatal estrogen exposure and estrogen-free diets, showing alterations in HoxC6 and target gene expressions and other phenotypic changes.&#x2028; Discussion: Based on our results, we will present a model in which HoxC6 is estrogen-responsive and coordinates mammary stem/progenitor cell homeostatic pathways, including FGF and GH-IGF1 signaling in the control of pool size and branching morphogenesis.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2010.
Heregulin induces Iressa-resistance of breast cancer cells through receptor heterodimerization.
Authors: Li J , Liu H , Espinoza I , Lupu R 
Published: December 2010

Abstract
Abstract #2016
Background: Heregulins (HRGs) are known as soluble secreted growth factors that are involved via binding and activating HER3 and HER4 cell surface receptors in cell proliferation, metastasis, survival, and differentiation in normal and malignant tissues. We have previously shown that up-regulation of HRG is sufficient for development of mammary tumors independently of estrogen stimulation and HER2 overexpression. Moreover, inhibition of HRG expression suppresses the aggressive phenotype by decreasing HER activation and reducing matrix metalloproteinase-9 activity. Therefore, HRG appears to be a key modulator of tumorigenicity and metastasis in triple negative breast carcinomas. Resistance to anti-epidermal growth factor receptor (anti-EGFR) therapies such as gefitinib is an emerging clinical problem. In this regard we have used MDA231, HS578T and BT549 cells to study potential mechanisms of gefitinib resistance. These cell lines are EGF independent and express high levels of HRG and resistant to gefitinib. Our hypothesis is that HRG signaling through HER3 induces resistance to EGFR blockade. To demonstrate this, we knocked down HRG expression by RNA interference (RNAi) in MDA231, HS578T, and BT549 cells.&#x2028; Material and Methods: Down-regulation of HRG is observed in MDA231, HS578T, and BT549 cells transduced with HRG siRNA lentiviral vector pRNAt-U6.2. Sensitivity to gefitinib was determined by MTT assays and soft agar assays. Each experiment was repeated at least 3 times, all data were analyzed by ANOVA. The level of significance was set at p &lt; 0.05.&#x2028; Results: Our results show that when comparing to their parental cells, all MDA231/HRGsiRNA, HS578T/HRGsiRNA and BT549/HRGsiRNA cells grew at a lower rate and become sensitive to gefitinib. Our results indicate that HRG can overcome the inhibitory effects of gefitinib on cell growth and HRG signaling allows at least in part, the acquisition of gefitinib-resistant phenotype.&#x2028; Discussion: Although the mechanism for the resistance is still under further investigation, our observation has implications for the effectiveness of anti-EGFR therapies in breast cancer where HRG induced receptor heterodimerization in EGFR-positive breast tumors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2016.
High resolution representational oligonucleotide microarray analysis (ROMA) suggests that TOPO2 and HER2 co-amplification is uncommon in human breast cancer.
Authors: McArthur HL , Tan LK , Patil S , Wigler M , Hudis CA , Hicks J , Norton L 
Published: December 2010

Abstract
Abstract #2023
&#x2028; Background&#x2028; Clinical studies relating TOPO2A expression or amplification by FISH have yielded inconsistent results regarding prediction of benefit from various drug therapies, particularly in the setting of HER2 amplification by FISH. Because HER2 and TOPO2A are relatively small genes that are close to each other, and because the relevant commercially-available FISH probes hybridize to DNA sequences beyond the genes of interest, there is significant potential for false positive results. We therefore conducted an exploratory study comparing HER2 and TOPO2A amplification by ROMA and FISH.&#x2028; Methods:&#x2028; Forty-two archived formalin-fixed paraffin-embedded primary breast cancer specimens were pre-selected to contain 36 HER2 amplified and 6 HER2 non-amplified cases by FISH. These specimens were evaluated for HER2 and TOPO2A amplification by FISH at Memorial Sloan-Kettering Cancer Center and by ROMA at Cold Spring Harbor Laboratory in a double-blinded experiment. Two HER2 amplified by FISH specimens proved inevaluable for technical reasons. The results for the remaining 40 evaluable specimens were then compared.&#x2028; Results:&#x2028; Of the 40 evaluable specimens, the 6 cases selected as HER2 non-amplified by FISH were HER2 non-amplified by ROMA and TOPO2A non-amplified by both FISH and ROMA. Thirty-two specimens were HER2 amplified by both FISH and ROMA. Two specimens with HER2 FISH results of 2.2 and 2.4 did not demonstrate focal amplification by ROMA. Twenty-five (74%) of the 34 specimens with HER2 amplification by FISH were TOPO2A non-amplified by both FISH and ROMA (Table 1). However, only 2 (22%) of the 9 specimens with HER2 and TOPO2A co-amplification by FISH demonstrated TOPO2A amplification by ROMA.&#x2028; &#x2028; Conclusions:&#x2028; Our results suggest that by ROMA, the determination of HER2 status (amplified and non-amplified) and TOPO2A non-amplification by FISH is accurate. The absence of TOPO2A amplification in HER2 non-amplified breast cancer is consistent with published reports. We also confirmed the published frequency of HER2 and TOPO2A co-amplification by FISH. However, we found that co-amplification of HER2 and TOPO2A by ROMA is uncommon, which suggests that commercially-available FISH probes over-estimate the frequency of TOPO2A amplification in HER2 amplified cases. Studies evaluating the clinical implications of these findings are underway.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2023.
Phosphoproteomic study of breast cancer: quantitative analysis of SH2 binding proteins.
Authors: Machida K , Claffey KP , Thompson CM , Hong S , Shin D , Mayer BJ 
Published: December 2010

Abstract
Abstract #2034
Background: An important biological process involved in breast cancer cell is tyrosine phosphorylation. Particularly, two tyrosine kinases, Src and HER2, are over expressed in invasive breast cancer tissues and both are considered excellent prognostic markers and therapeutic targets. Since tyrosine kinases transduce downstream signals by phosphorylating substrate proteins, leading to cellular responses, we assume the status of tyrosine-phosphorylated proteins in tumors can also provide molecular markers for breast cancer. Recently we established a method termed SH2 profiling, in which a battery of Src Homology 2 (SH2) domains are used to profile proteomes based on interaction between SH2 domains and tyrosine phosphorylated proteins. In this study we developed a semi-automated method to quantify SH2 binding proteins on multiple blots, and explored the feasibility of SH2 binding patterns as potential molecular markers for breast cancer. Material and Methods: Protein lysates from 10 breast cancer patient tissues as well as cancer cell lines were prepared and loaded into multiple precast gels. Proteins were separated using a SDS-PAGE multigel apparatus and transferred onto nitrocellulose membranes. Blocked membranes were incubated with HRP-labeled GST-SH2 domain probes, and SH2 binding patterns were detected by chemiluminescence with a phosphorimager. To correct blot-to-blot variation, we produced a semi-automated imaging tool for multiple blots. SH2 binding proteins were individually quantified based on their molecular sizes on blots, and different breast cancer samples were compared using the SH2 binding profiles. Results and discussion: 1. We have developed a method to quantify and incorporate data from multiple protein blots, a task that is always challenging due to blot-to-blot variation. 2. Using the semi-automated quantitation approach, large numbers of SH2 binding proteins in breast cancer samples were analyzed. SH2 domains including Vav2 and Eat2 bound strongly to proteins even in HER-2 negative tumors suggesting activation of HER-2 independent tyrosine kinase signaling pathways in breast cancer. 3. Further development of the quantitation method is underway to determine if specific SH2 binding patterns are potential prognostic molecular markers for breast cancer. This study is supported by the Connecticut Breast Health Initiative, Inc.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2034.
Evaluation of CD83 antigen in the normal mammary epithelium and fibroadenoma human.
Authors: Borges MN , Silva ID , Silva BB , Araujo Neto JT , Facina G , Nazario AC 
Published: December 2010

Abstract
Abstract #2038
Background: The immune response initiation requests the capture and the presentation of the antigens to the specific lymphocytes. The cells that has this capacity are denominated antigen-presenting cells, and the dendritic cell (DC) is the one that has larger specialization degree for these functions. The DC maturation it is considered essential for the beginning of the immune response. The CD83 antigen is a co-stimulator, member of the immunoglobulin superfamily with 45Kd, and your expression is an important marker of the maturation of DC.&#x2028; Objectives: To analyze the CD83 antigen expression in the human's breast fibroadenoma and in the adjacent breast tissue and to identify the clinical features that can influence this expression.&#x2028; Material and Methods: It is a retrospective study where 29 histopathologic materials of breast fibroadenomas and the adjacent breast tissue, of 28 women in reproductive age, were analyzed. The immunohistochemistry method was used for analysis of the CD83 antigen expression and, subsequently, the cells were counted by light microscopy. A thousand epithelium cells of each case were analyzed (five hundred of the fibroadenoma and five hundred of the adjacent breast tissue) for statistical calculation of the expression or not of the antigen reaction in the cells. We used parametric test (t-Student) for statistical analysis of the results.&#x2028; Results: The CD83 antigen expression positive in the fibroadenoma's cells (365.52 ± 133.13) in relation to the adjacent breast tissue's cells (189.59 ± 140.75) was statistically greater (p &lt;0.001). Several clinical features were analyzed, however, only parity showed influence in the expression of the CD83 antigen in the adjacent mammary tissues, and the positive expression was more evident in nulliparous women (p=0.042).&#x2028; &#x2028; Conclusion: The CD83 antigen expression was statistically greater in the breast fibroadenoma's cells, when compared with the one of the adjacent breast tissue. No clinical variable influenced CD83 expression in the breast's fibroadenoma, however, it was significantly greater in the adjacent normal breast tissue of nulliparous women.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2038.
Genomic and transcriptomic differences between lobular and luminal ductal invasive carcinoma.
Authors: Gruel N , Raynal V , Lucchesi C , Pierron G , Fourchotte V , Cottu P , Sastre-Garau X , Fourquet A , Delattre O , Vincent-Salomon A 
Published: December 2010

Abstract
Abstract #2039
Background: Invasive lobular carcinomas (ILCs) of the breast are characterized by morphological and phenotypical features such as small, non cohesive, estrogens receptors positive cells, low proliferation rates with a metastatic spreading in numerous and different unusual metastatic sites as compared to invasive ductal carcinomas (IDCs) (Ferlicot et al, 2004). We have previously shown that ILCs presented the same outcome than IDCs (Sastre-Garau et al, 1996). Beyond E-cadherin genomic inactivation, little is known about the underlying genomic and transcriptomic alterations that may discriminate both subtypes.&#x2028; Aims of the study: To get an insight into ILC biological specificities, we performed a combined genomic (aCGH), transcriptomic (Affymetrix U133A+B) and phenotypic analysis of a series of 24 lobular carcinomas and compared it to a series of 41 ER-positive IDCs.&#x2028; Results: Analysis of genomic copy number showed that ILCs and IDCs shared gains of the 1q11-q43 region and losses of 16q12.1-q24.2 and 17pter-p13.1 regions. ILCs presented the 22q12-q13 loss but not the 16pter-p11.2 gain and 11q23-q24 loss as observed in IDCs. Eight different regions of high level amplifications were found in 29% of ILC cases (7/24 cases). Only one region of amplification was recurrent and observed in 5 out of 24 tumors (21% of the cases). This recurrent region of amplification was localized on the 11q13.2 region and encompassed the Cyclin D1 (CCND1) and Cortactin (CTTN) genes. ILCs and IDCs had comparable overall survival rates, however, unsupervised hierarchical clustering of transcriptomic data showed that ILCs and IDCs clustered apart. Genes involved in cell adhesion and motility, lipid/fatty transport and metabolism and electron transport were differentially expressed between the two groups.&#x2028; Conclusions: This integrated analysis emphasized the biological differences between ILC and IDC and highlighted genes of interest that could be useful for diagnosis, and could be new putative therapeutical targets.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2039.