bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphovascular Invasion in BRCA Related Breast Cancer Compared to Sporadic Controls.
Authors: van der Groep P. , Heerma van Voss M. , Bart J. , van der Wall E. , van Diest P. 
Published: December 2010

Abstract
Background: Germline mutations in the BRCA1 and BRCA2 genes predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumours serves several purposes. Biomarkers can contribute to the selection of high-risk patients for genetic screening, help to identify the pathogenicity of so called “unclassified variant” mutations, and insight in the carcinogenetic pathways allows to develop new targeted therapies. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels, and are often of the medullary (like) type that has a low rate of lymphovascular invasion (LVI), we hypothesized that absence of LVI could characterize BRCA1 related breast cancer.Methods: A population of 68 BRCA1 and 10 BRCA2 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumour type.Results: LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P=0.54, OR=1.29, CI 0.58-2.78). No significant differences were found for the BRCA2 group either (P=1).Conclusion: LVI seems to occur as much in BRCA1 germline mutation related breast cancers as in sporadic controls. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation, indicating that these cancers may have specific vasculoinvasive properties.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6019.
Preliminary Study of Pre-Metastatic Niche (PMN) in Nonmetastatic Nodes for the Assessment of Metastasis Risk in Breast Cancer (BC).
Authors: Adamo V. , Ieni A. , Caristi N. , Scarfì R. , Barresi V. , Giuffrè G. , Adamo B. , Colonese F. , Ferraro G. , Ricciardi G. , Tuccari G. 
Published: December 2010

Abstract
Bone marrow-derived hematopoietic progenitor cells (HPCs) seem to participate in early spread of cancer cells by forming a peculiar and highly organized micro-environment called PMN. Identifying such HPCs in the PMNs is emerging as a key step in assessing risk of metastasis.In this preliminary study we analysed 294 axillar nodes (271 pN0 and 23 pN1a) obtained from 30 pts undergone surgery for breast ductal invasive carcinoma in the period 1998-2000.Pts mean age was 61.2 years (range 45-79); 9 pts (30%) were premenopausal and 21 (70%) postmenopausal; 13 pts (43.3%) had ER+, 10 (33.3%) PR+; MIB1 was ≤ 25% in 22 pts (73.3%), &gt;25% in 6 (20%), unknown in 2 pts. After a median follow-up of 81.27 mos (range 12–136), 14 pts are disease-free, 9 pts dead of metastatic disease. Involved sites were: 1 loco-regional, 7 bone, 3 lung, 4 liver, 1 brain.Samples were fixed in 10% neutral buffered formalin for 12-72 hrs and included in paraffin at 56°C; 4 mm thick sections were pre-treated in microwave owen in 10 mM citric acid, pH 6.0 and incubated overnight with the following poly/mono-clonal antisera: VEGF-R1 (Santa Cruz Biothechnology 1:400),CD 133(Abgent 1:80),CD 117 (DAKO 1:500),CD-34 (DAKO 1:50).Clusters of immunoreactive cells were evident with CD 117 and CD 34 in all nodes.A different degree of immunopositivity was found with VEGR-R1 and CD 133 antibodies for different sites of metastasis; in particular, the cases spread in lungs, liver and central nervous system were more immunoreactive, compared to those with bone localization. All nodes classified as pN1a showed no immunoreactivity.The prognostic significance of HPCs in PMN needs to be further investigated, especially in node-negative BCs. The immunomorphologic aspect of the lymph node microenvironment could have significant clinical implications, in order to optimize BC therapeutic strategies.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6024.
Retrospective Analysis of Pathologic Criteria in 446 Patients with pT1a and pT1b Breast Cancer: A Study from Two French Anti-Cancer Centers.
Authors: Dalenc F. , Comet B. , Lacroix-Triki M. , Charytanski H. , Chauvet M. , Ceugnart L. , Belkacemi Y. 
Published: December 2010

Abstract
Background: To assess the risk of recurrence and survival after locoregional and systemic treatment regarding biological features among women with a 1cm-maximal size of breast cancer.Material and Methods: Individual clinicopathological data were collected from 446 patients, treated in the Oscar Lambret and Claudius Regaud centers between 2003 and 2006. 5 patients had bilateral breast cancer. Median age was 59y (range: 26-92). None of the patient had node involvement, but patients could have isolated cells. Surgery consisted of lumpectomy, quadrantectomy or total mastectomy in 95%, 1%, 4% of the patients respectively. Sentinelle node biopsy and axillary dissection were performed in 87% and 13% of the patients, respectively. Estrogen receptor (ER, n=447) and Progesterone receptor (PR, n=448) were determined from tumor tissue microarrays using immunohistochemistry (IHC). Cut-off used for ER and PR positivity was 10% of stained cells. Radiation therapy was delivered to 432 breasts (96%; 45-50Gy) and a boost to 296 (69%; 6-16Gy). Nodal RT was delivered in 29% of the patients. Systemic therapy consisted of hormonotherapy in 380 (85%) including aromatase inhibitors in 38%. Chemotherapy was administered in 18 patients. Only two patients received 1 year of trastuzumab.Results:Pathological tumor size was ranged between 1.0 and 10.0 mm (median: 8.0 mm). The majority of tumors (n= 383 or 85%) were ductal infiltrant carcinoma and 42 (9%) were lobular infiltrant. 189 tumors (48%) contained a ductal carcinoma in situ component. 11/381 (3%) presented lymphovascular invasion. The majority were grade III (n=194 or 45%). Only 53 tumors (12%) were ER negative and 129 (28.8%) were PR negative. Nineteen (5.2%) tumors and 4 (0.9%) patients presented tumors with Her 2 overexpression or gene amplification, respectively.After a median survival of 26 months, 8 patients presented locoregional or distant recurrence. Local, locoregional, and distant metatstases were observed in 3, 2 and 4 patients. Among these 8 patients ¾ were aged more than 50y, all of them had tumors &gt; 5mm and grade II or III. 6 out of the 9 patients were HR+. Presences of lymphovascular invasion and Her2+ status were not correlated to recurrence.ConclusionMammographic screening increased the rate of small tumors diagnosed and reduces mortality in breast cancer. It is not known if this reduction is more pronounced in certain groups of patients. In the new era of tumor biology new markers that could predict the sensitivity of tumours to local and systemic therapy have to be determined in further studies for more tailored treatments in small tumors. Further pathologic analyses are ongoing and will be presented.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6026.
Benefit of the Sequential Administration of Docetaxel after Standard FEC Regimen for Node-Positive Breast Cancer: Long-Term Follow-Up Results of the FNCLCC-PACS 01 Trial.
Authors: Coudert B. , Campone M. , Spielmann M. , Symann M. , Eichler F. , Serin D. , Delozier T. , Romieu G. , Canon J. , Orfeuvre H. , Piot G. , Petit T. , Chollet P. , Jerusalem G. , Audhuy B. , Veyret C. , Beauduin M. , Eymard J. , Martin A. , Roché H. 
Published: December 2010

Abstract
Objective: To evaluate the long-term impact on disease-free survival (DFS) and on overall survival (OS) of the sequential administration of docetaxel (D) following FEC100 among patients (pts) with node positive, operable breast cancer.Patients and Methods: Pts with localized, resectable, non pre-treated, unilateral breast cancer were randomly assigned to receive either Arm A: 6 cycles of FEC100 (5FU/epirubicin/cyclophosphamide 500/100/500 mg/m² day 1, every 3 weeks), or Arm B: 3 cycles of FEC100 followed by 3 cycles of docetaxel (D) 100 mg/m² (day 1, every 3 weeks). First chemotherapy cycle was to be started no more than 42 days after surgery. Radiotherapy was mandatory after conservative surgery and hormone therapy was given for 5 years if tumors were positive for at least one hormone receptor. Main inclusion criteria were: age &lt; 65 years, at least one positive node, no metastasis and normal cardiac, hematologic and renal functions. The main end-point of this prospective, non blinded, randomized, multicentre phase III trial was the 5-year DFS. These results have been already published (Roché et. al. J Clin Oncol. 2006 24(36):5664-71). Since this first analysis, survival data have been updated.Results: Between June 1997 and March 2000, 1999 pts were recruited. Main pts characteristics were well balanced between the 2 arms: median age 50 years, conservative surgery 57%, grade III 39%, both HR negative 21%, both HR positive 60%, 1-3 involved nodes 62%. Treatment was completed for 95% and 93.4% of pts in arms A and B, respectively.As of 15 April 2009, with a median long term follow-up of 92.8 months, 639 pts have experienced at least one event: 124 loco regional relapses, 421 metastasis, 68 contra lateral breast cancer, and 26 deaths as first event. A total number of 71 second cancers and 383 deaths have been registered.8-year DFS rates were 65.8% with FEC and 70.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 15% reduction in the relative risk of relapse with FEC-D (HR = 0.846 [95%CI 0.724 – 0.988], p=0.03).8-year OS rates were 78% with FEC and 83.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 25% reduction in the relative risk of death with FEC-D (HR = 0.754 [95%CI 0.616 – 0.922], p=0.006).Conclusion: Initial report of 5-year benefit in DFS and OS with sequential administration of FEC followed by D are fully confirmed at 8 years.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 603.
Tumour Aromatase Expression, a Prognostic for Local Control in Young Breast Cancer Patients after Breast-Conserving Treatment?
Authors: Bollet M. , Savignoni A. , De Koning L. , Tran Perennou C. , Barbaroux C. , Degeorges A. , Sigal-Zafrani B. , Almouzni G. , Cottu P. , Salmon R. , Servant N. , Fourquet A. , de Cremoux P. 
Published: December 2010

Abstract
Introduction: To determine whether the levels of expression of 17 candidate genes were associated with locoregional control after breast conserving treatments of early-stage breast cancers in young, premenopausal women.Methods: Gene expression was measured using RT-PCR in the breast tumors of a series of 53 young (≤40 years), premenopausal patients. All treatments consisted in primary breast conserving surgery followed by whole-breast radiotherapy (+/- regional lymph nodes) with or without systemic treatments (chemotherapy +/- hormone-therapy). The median follow-up was 10 years.Results: The 10-year locoregional recurrence rate was 70% (95% CI 57%-87%). In univariate analysis, no clinical/pathological prognostic factors were found to be significantly associated with a decreased loco-regional control. Expression of three genes was found to be significantly associated with an increased loco-regional recurrence rate: low estrogen receptor beta, low aromatase, high GATA3. Two others were associated with only a trend (p&lt;0.10): low HER1 and SKP2. In multivariate analysis only the absence of aromatase was significantly associated with an increased loco-regional recurrence rate (p=0.003, Relative Risk=0.49 95% CI [0.29-0.82]).Conclusions: Recent data give credit to the fact that breast cancer in young women is a distinct biological entity driven by special oncogenic pathways. Our results highlight the role of estrogen signalling pathways (mainly CYP19/aromatase, GATA3 and ERβ) in the risk of locoregional recurrence of breast cancer in young women. Confirmation in larger prospective studies are needed.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6035.
Identification of an Adverse Biologic Profile in Cyclophosphamide/Metotrexate/5-Fluorouracil Treated Early Stage Breast Cancer Patients by Immunohistochemical Analysis of PI3K/p-Akt Pathway Alterations.
Authors: Mottolese M. , Novelli F. , Di Benedetto A. , Melucci E. , Sperduti I. , Perracchio L. , Buglioni S. , Vici P. , Nisticò C. , Pinnarò P. , Fabi A. , Bria E. 
Published: December 2010

Abstract
Background: Akt activation through PI3K, leads to the phosphorylation of p27 protein thus avoiding nuclear entry and inducing mislocation to the cytoplasm of the protein with consequent inhibition of p27 cell cycle inhibitory function. The prognostic role of PI3K/Akt pathway alterations correlating phenotypic profiles with bio-pathologic variables of known clinical importance have been investigated in a retrospective series of early stage breast cancer patients (BC pts) treated with cyclophosphamide/metotrexate/5-fluorouracil based chemotherapy (CMF).Materials and methods: p-Akt, PI3K and p27 expression were evaluated by immunohistochemistry in a series of stage I/II BC pts who underwent conservative surgery and were candidates to receive CMF adjuvant therapy plus radiotherapy. Multiple Correspondence Analysis (MCA) was used to identify sub-groups of pts with different prognosis, while uni- and multivariate Cox regression analyses were applied to determine the impact of parameters identified by MCA on 10-yrs Disease Free Survival (DFS), together with clinico-pathological features. Receiver Operative Curve (ROC) analysis was adopted for optimal cut-off values.Results: In a series of 133 pts, with a median follow-up of 107 months (range 40 to 141), those pts characterized by high Ki67 index, p53+, p-Akt+, PI3K+ and HER2+ (Adverse Biologic Factors, ABF) were associated with tumor relapse at the MCA analysis. ROC analysis dicotomized between pts with a Favourable Biological Profile (FBP, &lt;3 ABF) and Unfavorable Biologic Profile (UBP ≥ 3 ABF). UBP pts showed a significantly shorter 10- yrs DFS than FBP pts at Kaplan-Meier analysis (67.0% vs 91.3%, p=0.0006). According to the multivariate analysis, the biologic profile was the only significant prognostic indicator for longer DFS (p=0.002). Significant factors at uni- and multivariate analysis are shown in the table.Significant factors at uni- and multivariate analysisFactorsUnivariate (HR, 95% CI)p-valueMultivariate (HR, 95% CI)p-valueGrading3.32 (1.31-8.43)0.012--PgR2.37 (1.03-5.48)0.043--UBP4.24 (1.73-10.40)0.0024.24 (1.73-10.40)0.002 Discussion: These data suggest that the activation of Akt may contribute together with high Ki67 index, p53+, p-Akt+, PI3K+ and HER2+ in predicting recurrence in early stage BC pts homogeneously treated with CMF based therapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6036.
Validation of an Array CGH Test for HER2 Status Using Tumor-Targeted DNA Extraction from Formalin Fixed Tissue: Comparison with Fresh Frozen Tissue Results.
Authors: Gunn S. , Gorre M. , Mohammed M. , McCaskill C. , Hibbard M. , Barry T. , Yeh I. 
Published: December 2010

Abstract
Background: Recent clinical validation of a commercially available array CGH test (HerScan™) for determination of HER2 status in 97 cases of newly diagnosed breast cancer showed high accuracy and 97% concordance with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) results meeting the CAP/ASCO validation requirements for HER2 testing. However, the validation study was performed using fresh frozen tissue, a requirement which precludes the clinical use of array CGH in the majority of breast cancer workups. In this study, 55 additional cases with known HER2 status by IHC and FISH were analyzed by array CGH using a tumor-targeted DNA extraction method designed to achieve optimal results from formalin fixed paraffin embedded (FFPE) tissue.Methods: Tumor tissue from 55 cases of invasive ductal, invasive lobular, and one mucinous carcinoma was visualized and marked on H&E stained sections cut from the FFPE block, with targeted areas captured by slide scraping or 4mm punch. Following proteinase K digestion, DNA was extracted from known HER2 positive (n=25), HER2 negative (n=25), and HER2 equivocal (n=5) samples. Verification of high molecular weight DNA was accomplished by agarose gel electropheresis followed by analysis of the tumor genomes using the HerScan test, a 1524 clone whole genome BAC microarray including 64 probes targeting the HER2/TOP2A amplicons on chromosome 17q.Results: Concordance equivalent to fresh frozen tissue results (&gt;95%) was found between HER2 status obtained by IHC/FISH and array CGH on FFPE tissue. Five cases with equivocal results by IHC/FISH were resolved by array CGH and found to have unamplified partial chromosome 17 polysomy (n=4) and normal HER2 status (n=1). In addition, chromosome 17 status, overall genomic stability, and the presence of co-amplified genes including EGFR, MYC, MDM2, CCND1, and PDGFRalpha were clearly revealed by microarray evaluation in all cases.Conclusions: Array CGH analysis of DNA extracted from FFPE tissue provides a robust and accurate alternative for the clinical determination of HER2 status in newly diagnosed breast cancer. In addition, the complete genomic evaluation of core biopsy specimens afforded by array CGH allows clinicians to deliver personalized cancer care through incorporation of prognostic markers and potential therapeutic targets into treatment planning and prediction of disease outcome.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6038.
Impact of OncoType DXTM Recurrence Score and Tumor Size on Making Chemotherapy Decisions in Breast Cancer Patients.
Authors: Goodwin M. , Hughes J. , Diego M. , Frazier T. 
Published: December 2010

Abstract
Background: Oncotype DXTM is a 21 gene assay that calculates recurrence score(RS) and recurrence risk(RR) over 10 years. Despite the contention that this genomic assay is more accurate than tumor size(TS) and age in predicting outcome, these factors continue to have major impact in decision-making regarding chemotherapy(CT). We analyzed the impact of TS, RS, and age on the decision to give CT.Methods: An IRB-approved chart review of 105 lymph node(LN) negative patients with ER+ T1 and T2 tumors was performed, reviewing age, RS, TS, CT history, Her-2 status, and pathology. RS was low(0-17), intermediate(18-30), or high(&gt;30). TS was divided into T1a(0.1-0.5 cm), T1b(0.51–1.0 cm), T1c(1.1–2.0 cm), and T2(2.1-5.0 cm).Results: Mean patient age was 60.9 years(range 35-82 years). Average(AVG) RS was 20.9; AVG RR at 10 years, 13.6%. Mean TS was 1.5 cm(median 1.3 cm). Overall, 29 patients(27.6%) received CT; 76(72.4%) did not. AVG TS for CT patients was 1.8cm, AVG RS was 29.5, and AVG age was 56.4(range 35-75). Non-CT patients' AVG TS was 1.4cm; AVG RS, 17.7; AVG age, 62.6(range 44-86). 9 patients(8.5%) had T1a tumors with an AVG RS of 19.1, and no patient received CT. 25(23.8%) had T1b tumors with an AVG RS of 21.0, and 5(20.0%) received CT. 51(48.6%) had T1c tumors with an AVG RS of 20.4, and 15(29.4%) received CT. 20(19.0%) had T2 tumors with an AVG RS of 23.1; 9(45.0%) received CT. 41 patients(39.0%) had low RS: 4(9.8%) received CT; 37(90.2%) did not. AVG TS and RS were 1.6cm and 15.0 respectively for CT patients, and 1.5cm and 11.6 for no CT patients. 49 patients(46.7%) had intermediate RS: 13(26.5%) received CT; 36(73.5%) did not. AVG TS and RS were 1.9cm and 22.7 for CT patients; 1.3cm and 22.2 for no CT patients. 15 patients(14.3%) had high RS: 12(80.0%) received CT; 3(20.0%) did not. AVG TS and RS were 1.7cm and 44.7 for CT patients; 1.3cm and 39.3 for no CT patients. 10 patients were Her-2+, 5 with high, 4 with intermediate, and 1 with low RS. 7 had CT. 5 of the 15(33.3%) high RS patients were Her-2+. AVG RS for the Her-2+ patients was 36.2, and AVG TS was 1.9cm. AVG RS was 19.3 for the non-Her-2+ patients. 16 patients were &lt;50 years old. AVG TS was 1.5cm and AVG RS was 24.2. 8 received CT and 8 did not. 89 patients were ≥50. AVG TS was 1.5cm and AVG RS was 20.3. 21(23.6%) received CT and 68 did not. Discussion: AVG RS was 20.9 for all T stages. Overall, 27.6% of patients received CT. Of the 64 with RS&gt;18, only 25(39.1%) received CT; 4(9.8%) of low RS patients still received CT. Patients with larger tumors and younger age were more likely to receive CT. Neither RS, TS, nor age alone seemed to influence the final decision. Multiple factors are still considered by oncologists when making CT decisions, and conversely, patients may not accept CT despite high RS.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6039.
The Influence of Oestrogen Receptor (ER) Status on the Pattern of Recurrence in Early Breast Cancer.
Authors: Mansell J. , Angerson W. , Wilson C. , Doughty J. 
Published: December 2010

Abstract
IntroductionThere is an early peak in recurrence in women with early breast cancer (EBC). This may be related to underlying tumour biology or secondary to a reaction to surgery. We aim to determine if ER expression influences the pattern of recurrence.MethodsData from 3 centres in Glasgow of consecutive women with EBC diagnosed between 1995 and 2001 were examined. Recurrence was defined as invasive disease at any site. Patients were grouped as high ER (≥70% expression), low ER (&lt;70% expression) and ER negative. Kaplan Meier and Time dependent Cox survival analysis was performed.Results2779 women were included with a median follow up of 5.5yrs. 1915 (68.9%) had high ER, 310 (11.2%) had low ER and 554 (19.9%) were ER negative. At 5yrs the cumulative recurrence rates were 10.4% (9.0-11.8) vs. 19.2% (14.7-23.7) vs. 30.5% (26.6-34.4) respectively. Time dependent multivariate analysis showed that low ER and ER negative were significantly stronger predictors of recurrence within 2.5yrs from diagnosis than at later intervals (p = 0.024 and p &lt;0.001 respectively). The hazard ratios for recurrence within 2.5 yrs for low ER and ER negative groups were 2.23 (95% CI 1.41-3.54, p=0.001) and 3.68 (2.60-5.21, p &lt;0.001). Beyond 2.5yrs the respective hazard ratios were 1.12 (0.77-1.64, p=0.558) and 1.40 (1.03-1.90, p=0.031)ConclusionsWomen with Low ER expressing and ER negative tumours are initially at a significantly increased risk of recurrence compared with women with high ER expressing tumours suggesting that underlying tumour biology contributes to the initial peak in recurrence.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6042.