bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving NPI for breast cancer prognosis by including PR and HER-2 expression: own data and external validation set.
Authors: Van Belle V , Brouckaert O , Van Huffel S , Schlichting E , Synnestvedt M , Naume B , Christiaens M , Neven P 
Published: December 2010

Abstract
Abstract #1080
The Nottingham Prognostic Index (NPI) classifies primary operable breast cancer patients into good (NPI ≤ 3.4) , intermediate (NPI 3.4-5.4) and poor (NPI ≥ 5.4) prognostic risk groups [Br J Cancer 1987; 56: 489–92]. Studies indicate a significant short term prognostic role for estrogen (ER), progesterone (PR) and HER-2 receptor on disease free survival (DFS). We proposed at SABCS 2007 to add PR and HER-2 expression to the NPI called improved NPI (iNPI) defined as (NPI) + (HER-2) – (PR), with HER-2 and PR '1' in case of amplified HER-2 and any PR-expression and '0' otherwise.&#x2028; Internal validation of the iNPI was performed on 1928 breast cancer patients, primary operated between Jan 2000 and June 2005 at Univ Hospital Leuven. All patients were classified into any of the three NPI or iNPI risk group. Mean follow-up was 3.5 yrs and DFS was defined as previously stated [Breast Cancer Research and Treatment 2007; 106: S247-S247]. Out of the 601 patients classified as NPI low risk, 59 shifted towards the intermediate iNPI group. Comparison of DFS for the 59 shifted with the non-shifted patients from the low NPI class did not reveal a significant difference (p=0.129, log-rank test). 57 patients out of 935 and 136 out of 392 respectively classified as intermediate and high NPI group became high and intermediate risk according to the iNPI. In both cases, DFS of the shifted patients differed significantly from DFS of the non-shifted patients (p=&lt;.001 en p=0.029). DFS of the shifted patients with the iNPI group they where shifted to was not/marginally significant (p=0.856, p=0.462 and p=0.047 for low, intermediate and high NPI respectively).&#x2028; For external validation a dataset from the Breast Cancer Micrometastasis group in Oslo with 677 patients and known NPI, PR and HER-2 was used. Figure 1 confirms a significant difference between DFS of the shifted and the non-shifted patients within the highest NPI risk group (p=0.021). The difference in DFS between shifted and non-shifted patients was marginally non-significant (p=0.068) in the intermediate and non-significant in the low NPI group (p=0.116). The non-significant difference between DFS of the shifted groups with the DFS of the group they were shifted to was confirmed, with exception of the low NPI group (difference in systemic treatment) (p=0.040, p=0.621 and p=0.076 for low, intermediate and high NPI respectively).&#x2028; We confirm the results from an internal study at the Univ Hospital in Leuven on an external dataset. Inclusion of the PR and HER-2 status into the NPI results in more homogenate risk groups concerning DFS.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1080.
Benefit of the 70-gene profile for widely used guidelines: an answer to increased selection for adjuvant chemotherapy in breast cancer.
Authors: Knauer M , Retèl V , Bueno-de-Mesquita J , Rutgers E , van Harten W , Rodenhuis S , van de Vijver M , van 't Veer L , Linn S 
Published: December 2010

Abstract
Abstract #1084
Introduction:&#x2028; Risk assessment for breast cancer patients differs substantially among treatment guidelines. The NCCN, St.Gallen, Adjuvant!Online, and Dutch 2008 guidelines are less restrictive in comparison to the 2004 Dutch guidelines and Nottingham Prognostic Index, when selecting patients for adjuvant systemic treatment. The Dutch Institute for Healthcare Improvement (CBO) has introduced slight changes in the concept 2008 guidelines. Adjuvant systemic treatment is only advised when the absolute 10-years survival benefit is 5% or more. The new recommendations for adjuvant systemic treatment are based on survival tables used in the Adjuvant! software. The changes affect only node-negative patients aged 35 years: since 2008 patients with G2/G3 tumors &gt;1cm or every tumor &gt;2cm are advised to undergo adjuvant systemic therapy, while in 2004 this was the case for tumors G3&gt;1cm, G2&gt;2cm or every tumor &gt;3cm.&#x2028; Patients and Methods:&#x2028; Risk was assessed for 427 lymph-node negative (LNN) patients in the prospective RASTER-study (Bueno-de-Mesquita, 2007) and 151 LNN patients in the NEJM-series (van de Vijver, 2002). Clinical risk was calculated using the 2004 and 2008 Dutch guidelines. Genetic risk was assigned according to the result of the Amsterdam 70-gene signature. Survival analyses were done according to the univariate Kaplan-Meier-method.&#x2028; Results:&#x2028; Instead of 57% in 2004, in 2008 only 24% of patients were assigned to clinical low risk in the RASTER study, and 141 patients (33%) changed from low to high risk (p&lt;0.001). The rate of discordant findings between clinical assessment and 70-gene signature increased from 30% in 2004 to 41% in 2008 (p&lt;0.001, table 1). Similar results were obtained for the 151 patients of the NEJM-series (30% and 35% discordance for the 2004 and 2008 CBO guidelines, respectively). At 10 years follow-up, differences between the high and low risk categories according to the 2004, 2008 guidelines and the 70-gene profile, were best predicted by the latter: distant-disease-free survival (DDFS) log-rank p=0.002, p=0.11 and p&lt;0.001 respectively.&#x2028; &#x2028; Conclusion:&#x2028; As adjuvant systemic treatments become more effective, guidelines become less restrictive, resulting in more patients being selected for adjuvant therapy. Since newer treatment guidelines do not better predict survival, the magnitude of the 70-gene profiles benefit, which is defined as proportion of patients in whom over- and undertreatment can be avoided, depends on present guidelines for risk assessment and shows a remarkable increase.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1084.
Metaplastic breast carcinoma: clinicopathologic features and prognostic value of triple-negativity.
Authors: Lim K , Oh D , Chie E , Han W , Im S , Kim T , Park I , Nho D , Ha S , Bang Y 
Published: December 2010

Abstract
Abstract #1085
Backgroud Metaplastic breast carcinomas (MBC) are a rare type of breast cancer comprising &lt;1% of all invasive breast cancers and are generally characterized by hormone receptor and human epidermal growth factor receptor 2 (HER2) negativity. There is a paucity of information on prognosis according to hormone receptor and HER2 expression for these rare tumors. The aim of this study was to compare the clinical features and prognosis, between triple negative metaplastic carcinoma (TNMC) and non-triple negative metaplastic carcinoma (NTNMC).&#x2028; Material and Methods We retrospectively analyzed MBC patients treated at Seoul National University Hospital between 1996 and 2006. Pathologic, immunohistochemical findings and clinical outcome information were reviewed.&#x2028; Results fifty-one patients were identified. The median age at presentation was 45.8 years (range: 27.3-83.8). Median tumor size at diagnosis was 3.0 cm (range: 0.8-12.0). 34 cases (66.7%) were node-negative, 16 (31.4%) node-positive, and 1 (2.0%) were missing. Estrogen receptor (ER)/progesterone receptor (PR) yielded negative results in 49 cases (96.1%) and 48 cases (94.1%), respectively. HER2 overexpression by immunohistochemistry was negative in 41 of 51 (80.4%). At median follow-up of 40.8 months, the 5-year overall survival rate and disease free survival were 73.9% and 64.9%, respectively. Non-triple negativity (p=0.031) correlated significant with overall survival in multivariate analysis.&#x2028; Of the 51 patients, 39 (76.5%) were TNMC, and 12 (23.5%) were NTNMC. In TNMC and NTNMC group, median ages were 45.6 and 51.5 years and tumor sizes were 3.0 cm and 3.0 cm, respectively. There were 12 patients (30.8%) in TNMC and 4 patients (33.3%) in NTNMC for lymph node metastasis. Two groups did not differ significantly by age, tumor size, or nodal status. Positive rates for ER, PR and HER2 were 16.7%, 25% and 83.3% in NTNMC. The 3-year overall survival rates in TNMC and NTNMC were 91.4% and 61.9%, respectively (p=0.029). As regards to 3-years disease-free survival, there was no statistically significant difference between TNMC and NTNMC (p=0.694, 75.8% versus 75.0%).&#x2028; Discussion MBC mainly has triple negative features. However, in subgroup analysis of MBC, non-triple negative group displayed a poor prognosis compared with triple negative group, which is contrary to the case of invasive ductal carcinoma of breast. Further research exploring mechanism of this result.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1085.
Ki-67 gives additional prognostic information on St Gallen 2007 and Adjuvant! Online risk categories in early breast cancer.
Authors: Jung S , Han W , Lee J , Yu J , Ko E , Kim E , Moon H , Park I , Hwang K , Oh D , Kim T , Noh D 
Published: December 2010

Abstract
Abstract #1086
Purpose: We sought to determine the significance of Ki-67, one of the tumor cell proliferation indexes, as a useful prognostic factor in early breast cancer.&#x2028; Patients and Methods: 1,080 consecutive patients with stage I or II breast cancer operated between 1998 and 2003 were enrolled. Patients were categorized based on the 2007 St. Gallen consensus and Adjuvant! Online. The expression of Ki-67 in the tumor was assayed using immunohistochemistry (cut-off value: 10%).&#x2028; Results: Univariate analysis revealed that tumor size, lymph node involvement, histologic grade, estrogen receptor, progesterone receptor, bcl-2, and Ki-67 (≥10%) were significant for both overall survival (OS) and distant metastasis-free survival (DFS). Of them, lymph node involvement and high Ki-67 expression were identified as independent prognostic factors for OS at multivariate analysis. The survivals of intermediate- and high-risk groups according to 2007 St Gallen consensus were further separated by Ki-67 expression level (5-yr DFS rate=93.3% vs 86.6% for Ki-67&lt;10% and ≥10%, respectively in intermediate-risk group (p=.001); 5-yr DFS rate=83.1% vs 61.5% for Ki-67&lt;10% and ≥10%, respectively in high-risk group (p=.006)). The survivals of low- and high-risk groups according to Adjuvant! Online were further separated by Ki-67 expression level [5-yr DFS rate=97.8% vs 89.5% for Ki-67&lt;10% and ≥10%, respectively in low-risk group (p=.010); 5-yr DFS rate=90.4% vs 82.6% for Ki-67&lt;10% and ≥10% in high-risk group (p=.005)).&#x2028; Conclusion: Ki-67 was an independent prognostic factor for DFS and OS in early breast cancer, and could give additional prognostic information on the risk grouping by 2007 St Gallen consensus and Adjuvant! Online.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1086.
Vascular endothelial growth factor receptor 2 is a significant negative prognostic biomarker in triple-negative breast cancer: results from a controlled randomised trial of premenopausal breast cancer.
Authors: Ryden L , Ferno M , Stal O , Linderholm B , Ostman A , Jirstrom K 
Published: December 2010

Abstract
Abstract #1087
Background: Triple-negative breast cancer (TNB) is today an established phenotype of primary breast cancer recognized by estrogen (ER) negativity, progesterone (PgR) negativity and (human epidermal growth factor) HER2 negativity. The prognosis is poor and moreover patients with TNB dont benefit from established targeted drugs with antiestrogen therapies or trastuzumab. The role of other putative targets in TNB, like angiogenic markers and additional tyrosine kinase receptors is therefore a topic of interest in order to find effective targeted therapies improving the prognosis.&#x2028; Patients and methods: In a cohort of premenopausal breast cancer (n=564) randomized to adjuvant tamoxifen or no adjuvant treatment a tissue microarray was prepared from available primary tumors (n=500) and immunhistochemical (IHC) staining was performed including ER, PgR, HER2, vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGFR2), epidermal receptor growth factor (EGFR) and platelet derived growth factor ß (PDGFR ß). HER2 status was additionally defined using fluorescence in situ hybridisation (FISH). Data regarding Nottingham histological grade (NHG) and Ki67, node status, tumour size and age was also included. All included patients were used for descriptive analysis, whereas only untreated patients were included in survival analysis.&#x2028; Results: In the whole cohort 96 patients had a TNB phenotype characterized by low age, high NGH (p&lt;0.001), high Ki67-index (p&lt;0.001), T2 tumors (p=0.002), N-negativity (p=0.004. EGFR-positivity (p&lt;0.001) and tumor-specific VEGFR2 expression (p=0.03). TNB phenotype was not associated with VEGF-A or stromal expression of PDGFR ß, and was a significant prognostic factor for 10-year BCSS (HR 2.1 CI: 1.4-3.3) by univariate analysis in the untreated arm. The prognosis was further explored among TNB patients and VEGFR2 was a significant negative prognostic factor (HR 2.5 CI; 1.1-5.5) for 10-year BCSS, whereas VEGF-A , EGFR and PDGFR ß were not.&#x2028; Discussion: In a controlled randomized trial of premenopausal breastcancer, TNB was associated with worse prognosis. VEGFR2 was a significant prognostic biomarker for TNB patients which makes VEGFR2 a putative therapeutic target for this specific phenotype. Additional analysis of EGFR, VEGF-A and PDGFR ß did not add any prognostic information for TNB patients in this study.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1087.
HER2 status determined on pre operative biopsies and in operative specimens: concordance among immunohistochemistry (IHC) fluorescence in situ hybridization (FISH) and chromogenic in situ hybridization (CISH) techniques in the CRITHER study.
Authors: Arnould L , Roger P , MacGrogan G , Lannes B , Hayem C , Campana F , Balaton A , Penault-Llorca F 
Published: December 2010

Abstract
Abstract #1089
Background: In breast cancer, HER2 status is generally assessed by IHC or FISH on operative tissue sample and in situ hybridization techniques are standard tools for determining equivocal IHC 2+ overexpression and deciding the correct treatment for HER2-positive breast cancer patients. For the management of their patients, oncologists or surgeons sometimes ask for assessment of HER2 status on per cutaneous core biopsy (CB).The primary objective of the CRITHER study was to investigate concordance between the results of CISH, FISH, and IHC techniques on pre-operative CB samples for HER2 status compared with HER2 status determined by FISH on surgical specimen from a population of previously untreated non-metastatic breast cancer patients in France. Methods: Analysis was performed on samples from 260 patients recruited at 24 pathology centers for the period 2003 to 2006 inclusive. Recruitment was made on the basis of IHC obtained from operative tissue samples in order to obtain around 50% HER2-positive (3+), 30% HER2-negative (0/1+), and 20% HER2-equivocal (2+) cases. CISH and IHC were performed in parallel on the pre-operative biopsy and matched surgical specimen in the participating laboratories, and FISH on both specimens in each of four reference pathology centers. IHC staining was analyzed according to different scoring systems. Results: The rate of discordance between pre-operative CISH and operative FISH was 1.8% with 1.5% false-positives and 2.2% false-negatives (k=0.963; p&lt;0.001); the corresponding rate for pre-operative IHC (excluding equivocal IHC 2+ cases) and operative FISH was 1.5% with 1.6% false-positives and 1.4% false-negatives (k=0.953; p&lt;0.001). Comparison of pre-operative and operative samples showed expected low rates of discordance for CISH (0.85%; k=0.982; p&lt;0.001) and FISH (0.45%; k=0.991; p&lt;0.001), with no false positives in either case. Results for the IHC scoring system analyses on concordance will be presented at the meeting. Discussion: As expected, concordance for both CISH and FISH between pre-operative and operative results was excellent. There was a high rate of concordance for pre-operative CISH and IHC HER2 status determination on CB (excluding equivocal IHC 2+ cases) compared with operative FISH results in patients with previously untreated non-metastatic breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1089.
Meningeal carcinomatosis in patients with breast cancer: clinical features and prognostic factors in 91 patients from a single institution.
Authors: Gautier H , Guilhaume M , Bidard FC , Dieras VC , Pierga J , Livartowski A , Mignot L 
Published: December 2010

Abstract
Abstract #1090
Background&#x2028; Breast cancer is the leading solid tumor responsible for meningeal carcinomatosis (MC) and the incidence is rising. To date, there is no standard of care and few prospective trials. Intrathecal treatment is provided but the modalities remain controversial.&#x2028; Methods&#x2028; From our data base we recorded 91 patients with breast MC admitted to Institut Curie between 2000-2007. Lumbar punction was performed in all patients for cerebrospinal fluid (CSF) cytology, protein level and dosage of CYFRA 21. Intra-thecal treatment: methotrexate 15 mg day1 to 5 and hydrocortisone acetate day 1 with oral folinic acid rescue day 1 to 5 every two weeks.&#x2028; Results&#x2028; Median age was 53 years (range 30-78). Tumor type was ductal carcinoma (63%), lobular (28%), ER positive 74%, HER2 overexpressed 10% and triple negative 31%. All patients presented other metastatic site: bone (67%), liver (42%) lung (29%), brain (38%). The median interval between primary tumor and diagnosis of MC was 60 months.&#x2028; Amongst the 80 patients treated (87%) with intra-thecal MTX, clinical response was observed in 88% of cases. There was a strong correlation between clinical response and survival (p&lt;0.001). Normalization of cerebrospinal fluid cytology (CSFC) was observed in 13 % of patients and was associated with better survival: 13 months versus 2 months (p=0.003). Improvement of other biologic parameters as CSF protein and CYFRA 21 was observed in 17% and 80% of patients respectively. The median survival was 4.5 months (0-53). In multivariate analysis, prognostic factors were: performance status 3-4 (p&lt;0.0001), more than 3 chemotherapy regimens before MC diagnosis (p=0.04), lack of ER (p=0.04) and high CYFRA 21 at diagnosis (p=0.01). With these factors a prognostic score may select patients with a true benefit to IT MTX (20% survival &gt; 1 year) or patients for whom treatment will have no impact on survival (&lt; 3 months).&#x2028; Conclusion: This score has to be confirmed in prospective study and new modalities of treatments need to be evaluated according to the biology of disease.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1090.
Men attending a breast cancer risk evaluation clinic.
Authors: Vaz FH , Opinião AS , Rodrigues PC , Machado PM , Fragoso S , Santos S , Silva J , Moura C , Oliveira J 
Published: December 2010

Abstract
Abstract #1103
Background- Counselling for hereditary breast cancer risk has been mostly directed to women and their female counterparts. However, BRCA1/2 male carriers are at risk for several cancers and their motivation for counselling and follow up is mostly unknown.&#x2028; Material and methods- Review of individual and family records from all male pts counseled in our clinic from Jan2001-Dec2007.&#x2028; Results: eighty one male pts were counseled, 32 previously affected with cancer (mean age 61yrs) and 49 healthy men (mean 41 yrs). Mostly, all affected pts were refered to or invited to as probands for BRCA2 screenning. All but 2 of these accepted screening after counseling, being the concern with their offspring the main motivation for testing. With 3 exceptions all unaffected men were unvited for counselling due to the identification of BRCA2 mutations in their families: 6/49 refused or postponed genetic testing after counselling (mean age 39 yrs). All male BRCA carriers (total of 32) are BRCA2 positive: 12 index probands affected with Breast (10 cases, 3 bilateral) or prostate cancer ( 2 cases) and 20 healthy carriers under increased surveillance (yearly observations at the Breast Clinic + Dermatology and Urology). Psychosocial support is also available but only one male BRCA2 carrier, a prostate cancer survivor with previous depressive symptons, has this support regularly.&#x2028; Male carriers did adhere to increased surveillance and 5 neoplasias were diagnosed in 4 BRCA2 male breast cancer survivors: 3 cases of asymptomatic prostate cancer (Gleasons 9, 7 and 6 respectivly) 1 case of contralateral breast cancer and 1 case of gastric cancer. All 4 pts are alive without evidence of disease, after appropriate treatment. Conclusions: men belonging to BRCA families are at risk for several cancers and seem to adhere to genetic testing and surveillance. Guidelines for hereditary breast cancer management should be comphreensive and include orientations to counsell male individuals at risk.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1103.
Identification of urinary biomarkers to distinguish tumor bearing and control rats in the methylnitrosourea (MNU) – induced model of mammary carcinogenesis: use of label-free, comparative, ultra-high resolution nano-LC mass spectrometry.
Authors: Townsend RR , Rohrs H , Leduc R , Yi Y , Yao R , Malone JP , Edrman-Gilmore P , Grubbs CJ , You M , Lubet RA 
Published: December 2010

Abstract
Abstract #1109
In the MNU induced model of mammary cancer, rats given a single dose of MNU (75 mg/kg BW), via the jugular vein, at 50 days of age develop multiple ER+ mammary cancers. These cancers appear similar to highly differentiated ER+ human breast cancers, and have been shown to be sensitive to many of the same chemotherapeutic agents that are effective in women. When a female rat developed its first palpable cancer, it was placed in a metabolic cage and urine collected overnight on dry ice. The urine from these rats were compared to those obtained from control rats. Using a new sample preparation protocol, peptides were prepared from the urines of control (n = 4 individual animals) and rats bearing induced mammary tumors (n = 4). The peptide pools were analyzed using nano-LC-LTQ-FT-MS. The 8 LC-MS analyses were aligned and the integrated accurate mass signals were quantified using Rosetta ElucidatorTM software. The ion currents from 4430 peptides (charge state &gt; +2) were analyzed between the two groups using ANOVA. Two hundred and twenty nine peptides were found to be significantly different (P&lt; 0.01) between the two groups, with clear distinction between the urines from control and experimental animals being observed using hierarchical clustering and principal component analysis. The protein identifications that were significantly increased in the tumor-bearing urines were confirmed by targeted tandem mass spectrometry. Further studies relating the altered expression of these peptides to differences in tumor size, the effects of therapeutic agents, etc will also be presented.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1109.