bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-01-02: Flat Epithelial Atypia of the Breast on Core Needle Biopsies — To Re-Excise or Not
Authors: Uzoaru I , Morgan BR 
Published: April 2011

Abstract
Flat epithelial atypia (FEA) of the breast have a tendency to calcify, and as such, are becoming increasingly detected by mammography. There is no consensus yet on whether to excise these lesions or not after diagnosis on core needle biopsies (CNB). We reviewed 3948 consecutive mammotome breast CNB from our surgical pathology files between June 2004 and June 2009 correlating histomorphologic, radiological, and clinical features. Diagnosis of FEA was made based on the 2003 WHO definition (replacement of native epithelial cells by a single layer of mildly atypical cells often with apical snouts, or proliferation of a monotonous atypical cell population in the form of stratification of uniform, cuboidal to columnar cells generally up to 3-5 cell layers with occasional mounding). There were145 (3.7%) cases of pure FEA and 58 (1.5%) cases of concomitant FEA and atypical ductal hyperplasia (ADH). In the pure FEA population, the age range was 33-82 years (median 49 years) and 67 patients (67.4%) had calcifications on mammography. There were 95 patients of the pure FEA group who underwent subsequent excisional biopsies with the following findings: Benign-19(20%), ADH-36(38%), Ductal carcinoma in situ (DCIS)-1(1.05%), DCIS and invasive ductal carcinoma (IDC)-2 (2.10%), atypical lobular hyperplasia (ALH)-3 (3.15%). In the concomitant FEA and ADH group, the age range was 34-83 years (median 51.50), and 50 patients (86.2%) had calcifications on radiograph. Of these, 44 patients underwent subsequent excisions with the following findings: Benign-10(22.7%), DCIS-4 (9.09%), DCIS and IDC-2(4.54%), DCIS+lobular carcinoma in situ (LCIS) + Invasive lobular carcinoma (ILC)-1(2.27%), papillary carcinoma-1(2.27%), and tubular carcinoma-1(2.27%). The incidence of carcinoma in the FEA+ADH group is about 20% (9 out 44) and 3% (3 out of 95) for the pure FEA group. This difference is statistically significant (p=0.0016). The relative risk of carcinoma findings in the ADH+FEA group versus the pure FEA group is 6.4773, 95% CI: [1.8432, 22.76 24]. These findings suggest that pure FEA in spite of having an association with carcinoma, albeit a low association, has a greater association with ADH, a well known risk factor for development of breast cancer. The contentious issue, however, still remains what to do with FEA when diagnosed by CNB since there is no consensus on the clinical management. Additional studies are needed to further understand the natural history of these lesions and provide a guide for their management.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-02.
Abstract P6-01-04: Ductal Carcinoma In-Situ Associated with Triple-Negative Invasive Breast Carcinoma Is Often Immunohistochemically Distinct from Invasive Component
Authors: Simon RA , Karim TA , Zhang C , Steinhoff MM , Sung CJ , Quddus MR. 
Published: April 2011

Abstract
Background: Gene expression profiling studies have identified a sub-set of breast carcinoma known as basal-like carcinoma, which characteristically do not express estrogen receptor (ER), progesterone receptor (PR), or HER2neu (HER2). These triple negative invasive ductal carcinomas (TN-IDC) are associated with an aggressive clinical course and poor prognosis. Little information exists in the literature concerning ductal carcinoma in-situ (DCIS) associated with TN-IDC. We evaluated the frequency, histologic features, and receptor status of DCIS associated with TN-IDC.
Design: From our institutional archives between July 2006 and August 2009, we retrieved all cases of intermediate and high grade invasive ductal breast carcinoma. Based on the immunoprofiling, invasive carcinomas were categorized into either TN-IDC or non triple-negative invasive carcinoma (non-TN-IDC). Immunohistochemistry for ER, PR, and HER2 was performed on the DCIS of the TN-IDC group and on some available cases from the non-TN-IDC group. The frequency, receptor status, and nuclear grade of DCIS associated with both groups were noted. Statistical analysis was performed using Fisher Exact Test. Results: Among a total of 224 cases, 56 (25%) were classified as TN-IDC and 168 (75%) as non-TN-IDC. DCIS was seen in 28 (50%) TN-IDC cases and in 150 (89.3%) non-TN-IDC cases (P&lt;0.0001). Sufficient tumor was available for immunohistochemical staining in 23 of 28 cases with DCIS in the TN-IDC group. Within the 23 cases, the DCIS were triple negative in 15 cases (65%). Of the remaining 8 cases (35%), 4 were positive for ER and PR, but negative for HER2, while the other 4 cases were negative for ER and PR but positive for HER2. Ninety-six cases in the non-TN-IDC group had available immunostains for review, 7 of which (7.3%) displayed a different receptor status from their invasive counterparts (p=0.0016, compared with TN-IDC). Two cases of non-TN-IDC showed an associated TN-DCIS. Of the 28 cases of TN-IDC associated with DCIS, 4 (14.3%) showed lower nuclear grade in DCIS than in its invasive counterpart, compared with 22 of 150 (14.7%) non-TN-IDC cases (no significant difference). One TN-IDC case displayed two distinct morphologic patterns of DCIS; neither pattern was triple negative.
Conclusion: Our study demonstrated the presence of DCIS in a considerable proportion of TN-IDC although at a significantly lower frequency than in non-TN-IDC. DCIS associated with TN-IDC was significantly more likely to display a different immunoprofile from its invasive counterpart than DCIS associated with non-TN-IDC.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-04.
Abstract P6-01-05: Long-Term Diagnostic Accuracy of Fine-Needle Aspiration Cytology Performed in a One Stop Clinic for the Diagnosis of Suspect Nodular Breast Lesions
Authors: Borget I , Vielh P , Canale S , Balleyguier C , Azoulay S , Garbay J-R , Bourgier C , Mathieu M-C , Delaloge S. 
Published: April 2011

Abstract
Background: Fine-needle aspiration cytology (FNAC) has been used extensively in the diagnosis of breast lesions, but false-negative rates are a matter of concern. Immediate onsite evaluation of breast lesions, combining FNAC results with clinical and radiological data allows improving its diagnostic accuracy. The objective of this study was to evaluate the diagnostic accuracy of a large series of FNAC of breast lesions during the first 3-year period of a dedicated one-stop clinic, by comparing the FNAC results with the corresponding definitive histological examination outcome or the results of the radiological follow-up at 18 months.
Method: Data of all consecutive patients (pts) whose lesions were prospectively characterized by ultrasonography (US) and diagnosed by FNAC in the one stop clinic of the Institute Gustave Roussy between May 2004 and March 2007. Histological verification by core-needle biopsy or surgery was systematically performed for lesions classified malignant or suspicious by cytopathology, and for benign lesions, when no perfect concordance between clinico-radiologic features and FNAC results (such as benign FNAC but BI-RAD 5) was found. For non-operated patients, follow-up consisted on biannual US and/or mammography; the results at 18 months were considered. Pts characteristics, radiological findings, cytopathological and histological results were extracted from the hospital computerized prospectively registered medical records. Complete sensitivity (number of carcinomas that were malignant or suspicious by cytopathology) and full specificity (benign lesions at cytology of the total number of benign lesions) were calculated by comparing the cytopathological results to the histological or the long-term follow-up status.
Results: A total of 1822 nodular breast lesions (mean size: 20 mm, BI-RAD ACR 1/2/3/4/5/unknown: 10/96/471/459/777/9) in 1739 pts (mean age: 56 years) were studied. FNAC was US-guided in 1115 lesions (61 %). Lesions were classified by FNAC as malignant in 842 (46%), benign in 771 (42%), suspicious in 154 (9%), and unsatisfactory in 55 (3%) cases. Complete sensitivity (number of carcinomas that were malignant or suspicious by cytopathology) was estimated at 98.5%, whereas full specificity (benign lesions at cytology of the total number of benign lesions) was equal to 94.4%. There were 4 false-positive lesions and 32 false-negative lesions, but all these lesions except one were operated as radiological results were suspicious of malignity.
Conclusions: Breast FNAC performed in a dedicated one-stop clinic with immediate on-site diagnosis presented a low rate of unsatisfactory specimens and a very efficient tool for triaging patients candidates for histological evaluation conversely for follow-up by imaging.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-05.
Abstract P6-01-09: HER4 Is Downregulated in Lymphnode Metastases Compared to the Paired Primary Breast Carcinoma
Authors: Brügmann A , Jensen V , Garne JP , Nexo E , Sorensen B. 
Published: April 2011

Abstract
Introduction: The Human Epidermal Growth Factor Receptor 4 (HER4) of the EGF receptor family has been characterized in both normal and malignant human breast tissue and HER4 overexpression has been shown to predict prolonged survival compared to HER4 receptor negative disease.
In our study we investigated the HER4 expression in normal breast tissue, primary breast carcinoma and in ipsilateral metastatic axillary lymphnodes at the time of primary breast cancer surgery.
Material and methods: Paired tissue samples from normal breast tissue and primary breast carcinomas were obtained from 169 patients. Out of these a third sample was obtained from 66 patients with metastatic lymphnodes. The primary tumour specimens were sampled uniformly at random. The mRNA expression of HER4 was quantified with real time RT-PCR and expressed relative to the householdgene (HMBS) in arbitrary units (arb.u.).
Results: The mRNA expression of HER4 was significantly higher in breast carcinoma with a mean of 2.26 arb.u. [95% c.i.:1.87 to 2.65 arb.u.] than in the paired sample of normal breast tissue with a mean of 0.82 arb.u. [95% c.i.: 0.47 to 1.16 arb.u.] (p=0.0001). The mRNA expression of HER4 was also significantly higher in breast carcinoma than in the corresponding lymphnode mean 0.75 arb. u. [95% c.i.: 0.43 to 1.07 arb.u.] (p=0.015). There was no significant difference observed in mRNA expression of HER4 between the metastatic lymphnode and the corresponding normal breast tissue (P&gt;0.05). When HER4 expression was compared between the primary tumours that had metastasised and those that had not, there was no significant difference (P&gt;0.05). Conclusion:
The HER4 expression was high in the primary tumour as compared to normal breast tissue and the corresponding lymphnode. In view of previously published relations between a low expression of HER4 and a poor prognosis our results warrant further studies in order to evaluate whether suppression of HER4 in tumour cells could be involved in lymphogenic metastatic spread.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-01-09.
Abstract P6-02-01: Meta-Analysis of Ductal Carcinoma In Situ (DCIS) on Core Needle Biopsy — Underestimation and Predictors of Invasion
Authors: Brennan ME , Turner RM , Ciatto S , Marinovich ML , French JR , Macaskill P , Nehmat H. 
Published: April 2011

Abstract
Background: A diagnosis of ductal carcinoma in situ (DCIS) on core needle biopsy (CNB) may represent an underestimate (or understaging) of invasive breast cancer (IBC). This is identified on excision histology in 4%-35% of CNB diagnoses of DCIS. It is of clinical significance as it may prevent informed discussion about management options for IBC and may mean that more than one surgical procedure is required. We systematically review the literature on CNB to report pooled estimates for underestimation of IBC following CNB diagnosis of DCIS and identify preoperative predictors of invasion.
Methods: Studies were identified by searching MEDLINE and were evaluated against predetermined inclusion criteria: data were extracted independently by 2 authors. We calculated study-specific proportions for DCIS underestimates. Using meta-regression (random effects logistic models) we investigated the association between study-level preoperative variables and understaged IBC.
Results: 47 studies met eligibility criteria reporting 6,213 cases of DCIS on CNB with excision histology as the reference standard.
Table 1: Pooled underestimation rates for
There were 1,482 underestimates (DCIS on CNB and IBC on excision); pooled estimate 25.9%(95% CI 22.2, 29.9). Preoperative variables associated with underestimation included ultrasound-guidance (vs stereotaxis), 14Gautomated (vs 11GVAB), high grade CNB lesion (vs nonhigh grade), size &gt;20mm, BIRADS 4/5 (vs BIRADS3), mammographic mass (vs calc only) and palpability.
Conclusion: Using available evidence we estimate that around 26% of CNB DCIS diagnoses represent understaged IBC. We identified preoperative variables associated with higher risk of understaging. This information can be used for preoperative discussion of management options, including possible sentinel node biopsy at the time of excision.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-02-01.
Abstract P6-04-03: Unique Recurrent Signature and Signaling Pathway of Asian Triple Negative Breast Cancer
Authors: Kuo WH , Chen HL , Hsiao CK , Chuang EY , Chang KJ. 
Published: April 2011

Abstract
Background: Triple-negative (TN) breast cancer, a lack of understanding of the driving oncogenic mechanisms and thus therapeutic targets has left this an understudied ‘Cinderella’ in breast cancer phase III trials. No publication has been addressed on recurrent signature and pathway signaling of Asia TN breast cancer. The gene expression difference between Eastern and Western breast cancer is also unknown.
Material and Methods: 185 represent breast cancer cases including 43 Luminal A, 31 Luminal B, 35 Her-2 type, 51 TN and remaining 25 unclassified were selected from our tissue bank. Using Agilent microarray chip, we explored gene expression profile of these patients. For direct western and eastern comparison, 195 Caucasian breast cancer gene expression profile using the same Agilent platform were downloaded wedsite. In TN breast cancers, excluding 3 cases with stage IV disease at diagnosis, 11 patients developed distant recurrence during follow up. For these 48 patients, recurrent model was established by two step Cox proportional hazard regression: in first step, 35 candidate recurrent genes were selected from 20173 genes with significant level less than 0.0005. Then, we randomly choose 4 genes from the 35 candidate genes to construct recurrent model to avoid overfitting. TN related signaling pathways were discovered using Ingenuity Pathway Analysis(IPA) and GSEA(Gene Set Enrichment Analysis).
Results: Using non-supervised analysis, we found the eastern and western breast cancers have their own TN cancer clustering phenomenon, obviously in a different cluster.
This represented the eastern and western breast cancer have fundamental differences. The model including PKRAG3, MORC2, GRB7, FAM43A showed the best recurrence prediction power in 52360 combination models(R Square 0.71). This model was cross-validated by Vector machine(SVM) with leave one out setting. The overall accuracy was 87.5%. The sensitivity and specificity were 72.7% and 91.9%. This model was failed to predict recurrence in Luminal or Her-2 Molecular type. With IPA, we found 9 TN related pathway. The top two were cAMP-mediated and Ephrin Receptor signaling. 10 pathways were found from GSEA. Nicotinate, Olfactory transduction and Axon guidance were on the top of the list. Further functional study is on going.
Discussion: This is the first study to compare the gene expression between eastern and western breast cancer on the same gene expression platform. The gene expression profile is fundamentally different between eastern and western TN breast cancers. This phenomenon infers different biological behavior and drug sensitivity may exist among different ethnic groups. We established recurrent prediction model unique for Taiwanese TN breast cancer by four genes with high accuracy. We can develop commercial recurrent kit after further clinical validation.
Figure available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-04-03.
Abstract P6-04-07: Pathway Activation Probability Score Analysis Reveals Patterns of Pathway Deregulation in Inflammatory Breast Cancer
Authors: Van Laere S , Van der Auwera I , van Dam P , Vermeulen P , Dirix L. 
Published: April 2011

Abstract
Background: Inflammatory breast cancer (IBC) is the most aggressive manifestation of primary epithelial breast cancer and differs from non-IBC both from a clinical and a biological perspective. The high metastatic potential of IBC is highlighted by the low 5-year survival rate of 50%. In the past, we demonstrated that IBC is characterized by a specific molecular profile, partly mediated by increased NFkB-activation. In the current study we aim to identify additional molecular alterations responsible for the altered gene expression profile.
Methods: We profiled 46 IBC samples and 56 non-stage matched nIBC samples using the Affymetrix HGU133plus2 platform. Using a set of recently published gene signatures (Gatza et al, PNAS, 2010) we calculated the activation probability scores for 18 distinct pathways (ER, PR, HER2, P53, P63, EGFR, RAS, SRC, TNFa, INFa, INFg, TGFb, STAT3, E2F1, PI3K, AKT, CTNNB and MYC). Unsupervised cluster analysis was performed on the IBC samples only to identify IBC-specific transcriptional heterogeneity. The silhouette-algorithm was used to test the robustness of clustering. Supervised analysis was performed to compare IBC to nIBC. All P-values were FDR-corrected.
Results: Using only IBC samples, unsupervised hierarchical cluster analysis identified four robust sample clusters (Average silhouette width = 0.345; P&lt;0.0001). Interestingly, the primary bifurcation of the resulting dendrogram is determined by INFa-, INFg-and TNFa-signalling. In addition to ER-, PR-, HER2- and P53-signalling, the transcriptional heterogeneity in IBC is also determined by AKT-, RAS-, STAT3- and TGFb-signalling. When comparing IBC to nIBC we identified 12 pathways that are differentially regulated (P&lt;0.05). Out of these 12 pathways, 4 (CTNNB, PI3K, E2F1 and P63) did not reveal any IBC-specific heterogeneity and all of these were hyperactivated in IBC. Interestingly, the PI3K-, E2F1- and P63-pathways form a tightly correlated signaling nodule (Spearman correlation coefficients &gt; 0.65, P&lt;0.001). Conclusions: In this study we demonstrated that IBC is transcriptionally heterogeneous and this heterogeneity is mainly determined INFa-, INFg-and TNFa-signalling. Also, we identified four pathways (CTNNB, PI3K, E2F1 and P63) which are differentially regulated in IBC as compared to nIBC but which do not contribute to the establishment of transcriptional heterogeneity within IBC. Therefore, we reason that these pathways can be added to the molecular repertoire of IBC.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-04-07.
Abstract P6-05-01: Triple Negative Breast Cancer in Korea — Distinct Biology with Different Impact of Prognostic Factors on Survival
Authors: Lee JA , Bae JW , Jung Y-H , An H , Lee ES. 
Published: April 2011

Abstract
Background: Patients with triple negative breast cancer(TNBC) are known to have poor prognosis and derive no benefit from endocrine therapy or targeted treatments. Using a database from a multicenter registry in Korea, we present the clinical features and prognosis for TNBC with other subtypes of breast cancer and clinicopathologic variables that influence the 3-year survival of the TNBC patients.
Materials and Methods: From 1993 to 2008, patients diagnosed with breast cancer who were registered to the Korean Breast Cancer Society Registry were analyzed retrospectively. A cohort of 26,767 patients were divided in four groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+, HER2+), HER2 overexpression (ER-, PR-, HER2+), and triple negative (ER-, PR-, HER2-). Clinicopathologic features such as age, tumor size, nodal status, p53, ki-67 expression and survival were evaluated. Results: The luminal A (14437 patients, 53.9%) subtype was the largest in our study sample, as compared with luminal B (3517 patients, 13.1%), ER-/HER2+ (3227 patients, 12%), and TNBC (5586 patients, 21%) subtypes. Compared with luminal A subtype, TNBC correlated with younger age and more aggressive characteristics, such as larger size, more lymph node metastasis, and higher proliferation rate. Moreover, TNBC correlated with poor overall survival and breast cancer-specific survival. The hazard rate showed a peak at 24 months for the TNBC subtype, but after 60 months, the risk was similar to that of the luminal A subtype. Higher T, N stage and histologic grade, and lymphatic and vascular invasion showed poor prognosis in TNBC patients, but on multivariate analysis only histologic grade and ki-67 status were related to poor prognosis. Young age was related to poor prognosis in the luminal A subtype, however, age was not related to prognosis in the TNBC subtype. Of the 5586 TNBC patients, 282 patients (7.11%) expired within 3 years of diagnosis. T and N stage, and grade was significantly associated with prognosis on multivariate analysis.
Discussion: TNBC subtype is characterized by a younger age with poorer outcome. However, younger age is not related to prognosis, and mortality risk decreases to that of the luminal A subtype, which is known to have the best prognosis after a few years. The underlying biology of the TNBC subtype is important, and further studies to discover novel biomarkers to predict prognosis and target treatments for the TNBC subtype are necessary.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-01.
Abstract P6-05-07: Molecular Classification of Breast Cancer: Clinical Correlation and Outcome in a Venezuelan Population
Authors: Mackarem G , Duran B , Vilchez L , Sierra M , Bracho E , Colina J. 
Published: April 2011

Abstract
Background: Gene expression analysis has defined several subtypes of breast cancer that differ in prognosis and response to therapy. Distribution of clinical, pathological features and outcome was performed among Venezuelan women diagnosed with breast cancer. The objective of this study was to evaluate clinical features and outcome. Material and Methods Of 1004 women treated at the BCTC between January 1, 2000 and April 30, 2010, 624 patients had assessable data for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER 2/neu). Molecular subtypes were defined as Luminal A (ER+, PR+, HER 2-), Luminal B (ER+, PR+, HER 2+), Basal Like (ER-, PR-, HER 2-) and HER 2/neu (ER+, PR+, HER 2+). Clinical and Pathologic features were available for all 624 patients. Follow-up (FU) for distant recurrence (D.R.) and deaths were available for 514 patients (survival and distant disease free survival). Data was compared for women younger than 50 years with those 50 and older
Results Median FU was 33 months. 268 patients (43%) were 49 years or younger and 356 were 50 years (57%) or older.
Discussion: Distribution of molecular subtypes in Venezuelan women is different than other ethnicities. This study also revealed that both age subgroups in the HER2/neu subtype had the worst outcome followed by patients under 50 in the Basal subtype.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-05-07.