bluuebunny/crossref_metadata_2025_split huggingface dataset:
RFA for Small Breast Cancer — What Tumor Can Be Treated Safely?
Authors: Takahashi M. , Hosoda M. , Takahashi H. , Matsuno Y. , Todo S. 
Published: December 2010

Abstract
Breast conserving surgery for small breast cancer has been acceptable as one of standard treatments. However, there are some patients who do not be satisfied with the cosmesis. The aim of this study is to verify the clinical safety and usefulness of the RadioFrequency Ablation (RFA) for small breast cancer without resection. Between January 2006 and Octobar 2007, 20 breast cancer patients were performed RFA with cool-tip RF system after sentinel LN biopsy under general anesthesia. All patients has consented as a clinical research, beforehand. MR mammography was performed after 3 and 6 months of follow-up. All patients were performed postoperative histological examination by 8G-needle mammotome biopsy after 6 months MRI evaluation.Tumor viability after RFA was assessed by hematoxylin -eosin and ssDNA staining. QOL after RFA was assessed both subjectively(QOL-ACD score) and objectively(JBCS cosmesis criterion). Preoperative mammotome revealed 4 patients had DCIS and 16 patients had IDC. The patients median age was 53 years old. The mean greatest dimension of tumors was 1.0 cm (range, 0.5-1.5 cm). MRI showed the dimention of coagulation necrotic area by RFA treatment was 3.5cm (range, 2.5-5.4 cm).All patients have been performed postoperative histlogical examination by 8G mammtome biopsy 6 month after RFA treatment. Coagulation necrosis of the tumor was complete in 20of 20 patients (100%).No patient was troubled skin burn. Neither local and distant recurrence has occurred in all patients (median follow up was 30 month). To treat RFA for breast cancer more safely, we analyzed factors which influenced the size of necrosis. Patient age, body mass index (BMI), background concentration measured by MMG, Fat involvement measured by CT did not influence with the size of nectosis (P=0.21,0.17,0.64,0.40). The state of posterior echo detected by ultrasonography was associated with the size of necrosis (p=0.045). Hence, RFA for the tumor with rich fiber such as scirrhous type tend to make necrosis wider than one with poor fiber such as solid tubular type.Most of patients were satisfied with the cosmesis of the RFA treated breast. Objective QOL score (JBCS cosmesis criterion) showed splendid cosmetic outcome. RFA is one of the effective local treatment for small breast cancer (&lt; 1.5 cm in diameter), and bring breast cancer patients cosmetic satisfaction.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4119.
Locoregional Recurrence with Breast Conservation Surgery and Radiotherapy after Neoadjuvant Chemotherapy.
Authors: Lee S. , Shin K. 
Published: December 2010

Abstract
Purpose; Breast conservation surgery (BCS) and radiotherapy(RT) after neoadjuvant chemotherapy (NEO) has concerns of high locoregional recurrence (LRR) rates. This analysis was done to know LRR rates and the variables increasing LRRs.Patients and Methods; 242 breast cancer patients treated with BCS and RT after NEO between 2001 and 2006 were included in this study. All patients were clinically node positive by positron emission tomography. Clinical stage at diagnosis (2003 AJCC) was IIA in 22.7%, IIB in 43.0%, IIIA in 33.5% and IIIB in 0.8% of patients. Of the patients, 51.4% received anthracycline-based NEO, 34.2% received a taxane, and 14.4% received anthracycline combined taxane regimen. RT was done to all patients.Results; At a median follow-up of 56 months (range, 14 - 86 months), 24 patients (9.9%) had developed LRR. Among these, 18 (7.4%) were ipsilateral breast tumor recurrences (IBTR), 2(0.8%) axilla, 3 (1.2%) supraclavicular and 5 (2.1%) internal mammary recurrences. Five-year actuarial rates of IBTR-free and LRR-free survival were 86.9% and 84.4%, respectively. Distant metastases were detected in 36 patients (14.9%). On multivariate analyses of LRR, adjuvant hormone therapy, pathological lymph node status and clinical stage were associated with higher rates of LRR. The hazard ratios for lack of hormone therapy, pathological nodal stage N2-3, and clinical stage III were 8.9 (95% CI, 3.5 to 23.1; p&lt;0.0001), 4.3 (95% CI, 1.7 to 11.2; p=0.003) and 2.7 (95% CI, 1.1 to 6.5; p=0.02), respectively. 5-year actuarial LRR-free survival rate was 86.5% in patients with adjuvant hormone therapy while it was 76.8% in patients without adjuvant hormone therapy.Conclusion; BCS with RT after NEO results in acceptably low rates of IBTR and LRR in clinical node positive patients. The adjuvant hormone therapy, pathologic lymph node status and clinical stages predict higher rates of LRR.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4120.
miR-92 Is a Novel Regulator of ERβ1 Expression in Breast Cancer.
Authors: Al-Nakhle H. , Burns P. , Cummings M. , Hanby A. , Hughes T. , Satheesha S. , Shaaban A. , Smith L. , Speirs V. 
Published: December 2010

Abstract
Down-regulation of ERβ1 expression is thought to contribute to carcinogenesis in the breast and consequently is seen in many breast cancers. The molecular mechanisms responsible for the down-regulation of ERβ1 remain unclear. microRNAs are a novel family of regulators of gene expression that have been shown to act on the expression of many critical cancer genes but their relationship with ERβ1 has not so far been demonstrated. The aims of this study were to establish whether miR-92 regulates ERβ1 expression, and whether this regulation plays a role in defining ERβ1 expression levels in breast cancers.Using a bioinformatics approach we initially identified potential binding sites for miR-92 within the 3' untranslated regions of ERβ transcripts using RNAhybrid software (http://bibiserv.techfak.uni-bielefeld.de/rnahybrid/). Two conserved target-sites for miR-92 were identified within the ERβ1 3'-UTR sequence contained within Genebank. We confirmed the expression of these UTRs in MCF7 cells. Next, we performed 3' RACE reactions to determine the 3'-UTR sequence of ERβ1 in MCF7 cellsWe used qPCR analyses of expression in paired normal breast and breast tumour samples (n=6) to examine the relative expression of miR-92 and ERβ1. Upregulation of miR-92 expression was observed in breast tumours compared with normal breast. An inverse relationship with ERβ1 expression was observed in these samples. In a separate cohort of breast tumours (n=36), a significant negative correlation between ERβ1 mRNA and miR-92 was observed (Spearman's correlation coefficient, r = -0.5, p=0.001). Elevated ratios of ERβ1 mRNA /miR92 were also observed in ERβ1 positive compared to ERβ1 negative cells lines.Inhibition of miR-92 in MCF-7 cells increased ERβ1 expression in a dose–dependent manner at RNA levels. Enhanced GFP reporter constructs containing miR-92 binding sites from the 3'-UTR of ERβ1 were used to determine whether miR-92 downregulates ERβ1 via the direct targeting of this 3'-UTR. Inhibition of miR-92 increased the translational efficiency (protein produced per unit of mRNA) of the GFP reporter, confirming that the miR-92 binding sites are a critical regulatory region. Finally, we showed that miR-92 expression was upregulated by 17β-estradiol and downregulated by tamoxifen in MCF7 cells (ERα+ ERβ+) but not in ERβ negative cells (BT20 and MDAMB453), suggesting ERs can mediate miR-92 regulation. Our results demonstrate that ERβ1 expression in breast cancer is regulated by miRNA-92.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4139.
Phosphorylation of Estrogen Receptor β at Serine 105 in Primary Breast Cancer.
Authors: Hamilton-Burke W. , Shaaban A. , Cummings M. , Holliday D. , Pollock S. , Horgan K. , Speirs V. 
Published: December 2010

Abstract
Background: Estrogen receptor (ER) α predicts response to hormonal therapy in breast carcinoma. The role of ERβ is less well understood. ER activities can be modulated by post-translational modifications including phosphorylation and phosphorylated ERα has been correlated with patient outcome. We investigated whether ERβ phosphorylated at Serine 105 (P-S105-ERβ) is expressed in breast carcinoma and assessed its potential clinical implications.Material and Methods: Tissue microarrays comprising 427 breast tumours (23% grade 1, 43% grade 2, 34% grade 3) with median follow up 118 months and 106 endocrine resistant breast tumours (15% grade 1, 41% grade 2, 44% grade 3) with median follow up 71 months were used in this study. Expression of P-S105-ERβ was studied by immunohistochemistry and analysed against clinical data. Regulation of P-S105-ERβ in vitro was assessed by immunofluorescence and Western blotting.Results: Expression of P-S105-ERβ was mainly nuclear and could be abolished by phosphatase pre-incubation, indicating specificity. In the first cohort Allred scoring ranged from 0 to 8 (median 6). Nuclear speckling was observed in 45% of cases. P-S105-ERβ correlated with ERβ1 (Allred score ≥ 3) and was associated with better overall survival (OS) and disease free survival (DFS) (p=0.028 and p=0.027, respectively). In a multivariate Cox hazard analysis, P-S105-ERβ overexpression was a significant predictor of better survival independent of tumor grade, lymph node status, size or ERα. In the endocrine resistant cohort Allred scoring ranged from 0 to 8 (median of 4) and the overexpression of P-S105-ERβ was also associated with improved OS and DFS (p=0.044 and p=0.033, respectively). Nuclear speckling was present in only 11% of cases. The difference in expression of P-S105-ERβ and association with survival outcome between the two cohorts was statistically significant. P-S105-ERβ was expressed in MCF-7 cells and in response to 17β-estradiol (E2); levels were raised within 30 min, and sustained for 24 hours. ERβ1 expression was unaffected by this treatment. Nuclear speckling was also observed and was markedly increased at 24 hours following E2 but not Tamoxifen.Conclusion: This is the first time to our knowledge that the expression of P-S105-ERβ in breast carcinoma has been investigated. Its presence in breast carcinoma and association with improved survival suggest P-S105-ERβ might be a useful additional prognostic marker in breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4141.
Receptor Conversion in Breast Cancer Metastases.
Authors: Hoefnagel L. , van der Wall E. , van de Vijver M. , van Diest P. 
Published: December 2010

Abstract
Background: Since breast cancer metastases are not usually biopsied due to their often inaccessible locations, choice of systemic treatment for metastatic breast cancer is usually based on tissue characteristics of the primary tumor, as determined by immunohistochemistry. However, pilot studies have shown that the immunophenotype of breast cancer metastases may be different from that of the primary tumor (“receptor conversion”). This means that many metastatic patients may not get the appropriate systemic treatment. The pilot studies published so far are however small and methodologically suboptimal as original staining data of the primary tumors were often used, and decalcified bone metastases were included that may give rise to false negative immunohistochemistry. Therefore, definite conclusions that may chance clinical practice could not be drawn. The aim of this study was therefore to study receptor conversion for ERα, PR, and HER2 in a large group of (non-bone) breast cancer metastases, restaining all primary tumors and metastases with current optimal immuno-histochemical methods.Methods: A group of 150 distant breast cancer metastases from different distant sites (79 skin, 33 liver, 22 lung, and 16 brain) was immunohistochemically stained for ERα, PR, and HER2, and receptor expression was compared to that of the primary tumor.Results: Receptor conversion for ERα, PR and HER2 occurred in 6%, 27.4% and 2.7% of the 150 patients, respectively. Conversion was mainly from positive to negative for ER and PR, and from negative to positive for HER2. Receptor conversion seemed to occur especially in liver metastases (ER 9.1%, PR 36.4%, HER2 6.1%) while brain metastases showed no conversion for ER and HER2.Conclusion: Receptor conversion in breast cancer metastases indeed occurs, is rare for ER and HER2, but is more frequent for PR, and may be most outspoken in liver metastases. This underlines the importance of having breast cancer metastases frequently biopsied when possible. Alternatively, molecular imaging strategies are warranted for sites that are difficult to biopsy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4145.
FOXP1 as a Potential ER Coregulator in Human Breast Cancer.
Authors: Shigekawa T. , Shigekawa T. , Ijichi N. , Takayama S. , Tsuda H. , Ikeda K. , Horie K. , Osaki A. , Saeki T. , Inoue S. , Inoue S. 
Published: December 2010

Abstract
Estrogen activates the estrogen receptor (ER) by recruiting various coregulators and cofactors, resulting in transcriptional regulation of target genes. Recently, we have shown that the FOXP1 forkhead transcription factor is a novel androgen-regulated coregulator for the androgen receptor (Biochem Biophys Res Commun, 374, 388-93, 2008). However, its role in breast cancer is still unknown.Here, we investigated the expression pattern of FOXP1 by immunohistochemistry in a series of 110 invasive breast cancers and compared it with clinicopathological factors. The expression of FOXP1 was detected in nuclei in 76 cases (69.1%) and correlated with expressions of ERα (P=0.001) and progesterone receptor (PgR) (P=0.003), while there was no association with age, lymph node status, size, or grade. Expression levels of FOXP1 mRNA are investigated by qRT-PCR using samples selectively obtained from breast cancer specimens with laser microdissection system (Zeiss Axiovert + P.A.L.M laser microdisection system). ERα, ERβ, and PgR mRNA levels were also measured.Then, we examined expression and function of FOXP1 in human breast cancer MCF-7 cells that possess functional ERα. The expression level of FOXP1 mRNA was up-regulated by estrogen treatment. In addition, estrogen-responsive element-driven luciferase reporter analysis showed that exogenously transfected FOXP1 increased estrogen-dependent transcriptional activity. We also observed that FOXP1 overexpression and knockdown could modulate the growth of MCF-7 cells.Taken together, these findings suggest that FOXP1 plays an important role as a potential ER coregulator in human breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4149.
Relationships between Progesterone Receptor Isoforms and the HER Receptors and Ligands Network in 299 Primary Breast Cancers.
Authors: Révillion F. , Lindet C. , Lhotellier V. , Hornez L. , Bonneterre J. , Bonneterre J. , Peyrat J. 
Published: December 2010

Abstract
Background: The effects of progesterone are mediated by two distinct nuclear receptors, called PR-A and PR-B, which are encoded by a single gene. In the normal human breast, these two isoforms are co-expressed at similar levels of expression whereas breast cancer seems to be characterized by an unbalanced expression of PR-A and PR-B, with a predominance of either one of these two isoforms. In the present study, we analyzed the relationships between the PR isoforms and the HER receptors and ligands network in primary breast cancer.Materials and Methods: This study involves 299 breast cancer samples from patients operated in our institute for locoregional disease between May 1989 and December 1991. Since PR-A has no specific sequence to distinguish it from PR-B, the mRNA expression of total PR-(A+B) isoforms as well as those of PR-B were assessed. They were quantified by real time quantitative RT-PCR using TaqMan probes, as previously described for HER receptors (Epidermal Growth Factor Receptor EGFR, HER2, HER3, and HER4) (Pawlowski et al, Clin Cancer Res 2000;6:4217-25) and HER ligands (EGF, Transforming Growth Factor alpha (TGFa), amphiregulin (AREG), betacellulin (BTC), Heparin-Binding EGF (HB-EGF), Epiregulin (EREG), and neuregulins 1-4 (NRG1-4)) (Révillion et al, Ann Oncol 2008;19:73-80).Results: PR-(A+B) and PR-B mRNA levels strongly correlated with PR and ER protein levels determined by radioligand assay. PR-(A+B) were found to correlate positively to IGF1 receptor, and both isoforms correlated negatively to histoprognostic grading. Considering the HER receptor and ligands network, PR-(A+B) were positively correlated with HER3, HER4, EGF, AREG, while they were negatively correlated with EGFR, TGFa, HB-EGF, EREG, and NRG2. Similarly, a positive correlation was found between PR-B and HER3, HER4, EGF and AREG while PR-B correlated negatively to EREG, NRG3 and NRG4. Finally, PR-(A+B) expression (higher than the lower quartile) was significantly associated with a longer overall survival (p= 0.02, Kaplan-Meier analysis).Conclusion: Our results, demonstrating strong correlations between PR isoforms and HER receptors and ligands network, reinforce the observations (Proietti et al, Mol Cell Biol 2009;29:1249-65) demonstrating that cross-talk between PR and the HER family appears to be a hallmark of breast cancer growth.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4150.
Amplification of the Prolactin Receptor Gene in Mammary Lobular Neoplasia.
Authors: Tran-Thanh D. , Tran-Thanh D. , Arneson N. , Pintilie M. , Warren K. , Bane A. , O'Malley F. , O'Malley F. , Done S. , Done S. 
Published: December 2010

Abstract
Background: Lobular carcinoma in situ (LCIS) has long been considered a marker of increased risk of cancer in both breasts. However, recent studies have shown that it can behave as a non-obligate precursor lesion as well. The biology and natural history of LCIS still remains ill defined in part because it is a challenging lesion to study as it usually does not have an identifiable gross appearance and is only recognized in fixed tissue specimens.Material and Methods: Using array comparative genomic hybridization (aCGH) we have analyzed regions of amplification found in LCIS and adjacent invasive lobular carcinoma (ILC) in a series of thirteen cases of archival patient samples from our institution. Degenerate oligonucleotide primed (DOP) PCR was performed for whole genome amplification of the extracted DNA from microdissected tissue samples prior to microarray analysis. Analysis of microarray data was performed using Significance Analysis of Microarrays (SAM). Of the ten most amplified genes in LCIS (highest SAM scores), one was selected for quantitative real time PCR (Q-PCR) validation due to the limited amount of material available from these cases. Q-PCR validation was performed on samples from 8 cases of LCIS and invasive lobular carcinoma and 12 archival cases of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) for comparison.Results: Amongst the 10 genes with the highest SAM scores, the prolactin receptor gene (PRLR) was selected for further Q-PCR validation in our limited samples. Amplification of PRLR was confirmed by Q-PCR in 4/8 (50%) of cases of LCIS and 4/8 (50%) cases of ILC, compared to 0/12 (0%) cases of DCIS and 3/12 (25%) cases of IDC. When LCIS and ILC were combined into one group, there was more amplification of the prolactin receptor gene when compared to the DCIS and IDC group (p= 0.01). The level of amplification between the two groups also differed in the range of copy number values, which was lower in the ductal group (0.78-1.58, n=24) compared to the lobular group (0.92-3.68, n=16) (p&lt;0.05).Conclusion: We have identified the prolactin receptor as a potential molecular target in lobular neoplasia using array comparative genomic hybridization. In contrast, we have shown that the prolactin receptor may not be as important for the progression of ductal lesions. These results support the view that lobular and ductal carcinoma evolve along separate pathways. Validation of the expression of PRLR in a larger number of LCIS cases is warranted.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4151.
Expression Levels of Enzymes Related to In Situ Estrogen Synthesis and Clinicopathological Parameters in Breast Cancer Patients.
Authors: Saeki T. , Suzuki M. , Nakata T. , Shiotsu Y. , Ishida H. , Akinaga S. , Aogi K. , Utsumi T. , Harada N. 
Published: December 2010

Abstract
Background: Local estrogen synthesis may play an important role of progression of breast cancer with hormone receptors. Local progression of breast cancer may depend on high concentration of estrogens and estrogen receptor status. To clarify correlation between expression levels of enzymes in breast cancer and clinicopathological parameters, we analyzed expression of steroid sulfatase(STS), estrogen sulfatase(EST), 17b-hydroxyl steroid dehydrogenase type I & II(17b-HSDI & II) and aromatase. In addition, mRNA expression of estrogens receptor alpha(ERa), estrogen receptor beta(ERb), cycline D1 and erbB2 were measured. Material and Methods: The mRNA expression levels of genes in 196 breast cancer tissues removed from surgery were assayed by RT-PCR. Results: The level of STS were significantly higher in patients with clinical stage. STS expressed none in stage 0 or I, 0.011 in stage II, and 0.013 amol/1 amol b-actin in stage 3 or 4. In addition, EST expressed 58.5 amol/1 amol b-actin in stage 2 and 36.8 in stage 3 or 4, otherwise, the expression level of EST in stage 0 or 1 revealed 15.3 amol/1 amol b-actin. There were no correlation between clinical stage and aromatase expression. Expression levels of ERa and cyclineD1 significantly correlated with protein levels of ER, and there were significant correlation between erbB2 expression and prognosis of patients. Conclusion: Up-regulation of STS play an important role in tumor progression of breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4155.
MMP-3 and MMP-9 Gene Transfer Decrease Growth and Angiogenesis in Breast Cancer Xenografts In Vivo.
Authors: Bendrik C. , Dabrosin C. 
Published: December 2010

Abstract
Matrix metalloproteinases (MMPs) are largely implicated in tumor angiogenesis and metastasis due to their extracellular matrix (ECM) degrading capacities. Although MMP activity generally is discussed in terms of facilitating tumor invasion, MMP inhibition in clinical trials has failed. Moreover, increasing amounts of data show that MMPs may inhibit tumor progression by generation of potent anti-angiogenic factors such as endostatin from the tumoral stroma. We have previously shown that intratumoral gene transfer of MMP-9 induced tumor regression and reduced angiogenesis of breast cancer in vivo. If MMP activity induces tumor progression or regression may depend on type of MMP or expression levels of MMP in the tumor tissue. In this study we treated established breast cancers in nude mice with adenovirus vectors carrying the human genes of MMP-3 or MMP-9 in a dose response manner. Microdialysis was used to sample endostatin in situ and tumor growth was monitored for 35 days. Tumors in mice treated with low-dose of either MMP-3 or MMP-9 vectors exhibited tumor stasis throughout the experiment whereas high-dose gene transfer of either MMP-3 or MMP-9 induced significant tumor regression compared to controls treated with empty adenovirus vectors. The extracellular in vivo levels of endostatin were significantly increased in tumors treated with adenovirus carrying the MMP genes compared to controls. Tumors treated with high-dose MMP vectors also exhibited decreased microvessel area. Our results propose that increased expression of MMP-3 and MMP-9 have therapeutic effects of established breast cancer in a dose dependent manner where a slight increase of MMP expression results in tumor stasis and a high expression of either MMP-3 or MMP-9 by gene transfer results in a potent tumor regression.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4164.