bluuebunny/crossref_metadata_2025_split huggingface dataset:
P4-07-13: Prognostic Impact of Circulating Tumor Cells Assessed with the Cell Search Assay and Adna Test Breast in Metastatic Breast Cancer Patients – The DETECT Study.
Authors: Mueller V , Riethdorf S , Rack B , Wolfgang J , Fasching PA , Solomayer E , Aktas B , Kasimir-Bauer S , Mury D , Pantel K , Fehm T 
Published: June 2012

Abstract
Background
Over the last decade circulating tumor cells (CTC) were established as a prognostic factor in breast cancer patients. However, there are very limited studies comparing different test methods, although several are available.The DETECT trial for metastatic breast cancer patients was designed to investiate the prognostic impact of CTC. Here, we report on the prognostic relevance of CTC testing with different detection methods.
Material and Methods: Patients with primary metastatic breast cancer or metastatic recurrence were prospectively enrolled in this multicenter trial. CTC were detected using the FDA-approved Cell Search® assay applying immunocytochemistry and the RNA-based Adna Test Breast Cancer™. After a median follow-up of 11 months the first survival data are now presented.
Results: Both methods could be performed in 221 patients. Using the CellSearch™ assay 116 of 221 patients were CTC-positive based on the cut-off level of 5 cells. Presence of CTC was associated with the site of metastatic disease. The OS was 15.4 months in CTC positive pts. (95%-CI: 13.5−17.1 mths) compared to 20.4 mths. in CTC negative pts. (19.1−21.9 mths.; p&lt;0.001). In the multivariate analysis presence of CTC was the only independent predictor for overall survival (HR: 3.4, 95%-CI: 1.7−6.3) including tumorbiological factors, menopausal status, number and sites of metastatic disease. The progression-free survival was not correlated with CTC status in our cohort receiving different types of systemic treatment (p=0.197). When the AdnaTest Breast was performed, 88 of 221 (40%) patients were CTC positive. Except for HER2 status, no correlation could be observed between CTC positivity and any of the clinicopathological factors. CTC positivity assessed by the AdnaTest Breast has no impact on PFS and OS. A multivariate analysis was therefore not performed.
Conclusions: Currently, several different tests are available for CTC detection. Only a few tests have been approved by the FDA and been validated in large clinical trials. Therfore, it will be important to compare new techniques with the Cell Search assay.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-13.
P4-07-20: Apoptosis in Circulating Tumor Cells (CTCs) of Early and Metastatic Breast Cancer Patients.
Authors: Kallergi G , Konstantinidis G , Papadaki M , Agelaki S , Mavroudis D , Stournaras C , Georgoulias V 
Published: June 2012

Abstract
Background: Metastasis has been associated with the presence of circulating (CTCs) and disseminated (DTCs) tumor cells in peripheral blood and bone marrow of breast cancer patients, respectively. Recent studies have confirmed that the detection of CTCs and DTCs represents a strong and independent prognostic factor for decreased disease-free and overall survival. However, it is not clear so far whether all CTCs are capable to generate metastasis or some of them are destined to die. The aim of the present study was to analyze the presence of apoptotic CTCs in patients with early and metastatic breast cancer. Patients and methods: Double staining immunofluorescent (IF) expreriments were performed in peripheral blood mononuclear cells (PBMC) cytospins of patients with early (n=23) and metastatic breast cancer (n=29), prior to the initiation of adjuvant and first-line chemotherapy, respectively. Pancytokeratin A45-B/B3 antibody (as a marker of CK-positive cells) was coupled with either M30 (marker of apoptotic cells) or Ki67 (marker of proliferating cells) antibodies. Apoptotic CTCs were also evaluated using a polycaspase detection kit. Results: Significantly lower proportions of apoptotic CTCs were detected in metastatic compared to early breast cancer patients using the polycaspase kit (3% vs 49%, p=0.0001). These results were confirmed with M30 staining (32% vs 67%, in metastatic and early disease, respectively, p=0.023). The median percentage of apoptotic CTCs per patient was also lower in advanced compared to early disease patients (0% vs 100% with the polycaspase kit and 15% vs 70% with M30 staining). Ki67 positive CTCs were identified in 56% of early and metastatic patients, while the ratio of Ki67-positive/Total CTCs was 15% and 36% respectively. Conclusions: Apoptotic CTCs are more commonly observed in early compared to metastatic breast cancer, whereas, Ki-67 positive CTCs are more frequently encountered in metastatic disease. The differential incidence of apoptotic and proliferative CTCs in early and metastatic disease is probably related to disease progression. The evaluation of these markers in CTCs from patients with breast cancer may provide useful prognostic information and could be used to monitor the effectiveness of therapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-20.
P4-08-04: Preoperative Thrombin Pathway Activation Identifies Node Positive Patients in Early Breast Cancer.
Authors: Shaker H , Kirwan C , Landberg G , Bundred NJ 
Published: June 2012

Abstract
Activation of the thrombin pathway (TP) is seen in 50% of cancers and plays a significant role in promoting metastasis. Cancer-induced TP activation is exacerbated by surgery, and this activation may be greater in the presence of metastases.
Our aim was to determine if pre-operative plasma d-dimer, a marker of TP activation, correlated with the presence of LN metastases in early breast cancer. We also examined whether surgery-induced TP activation is affected by tumour-associated factors.
Methods
Plasma d-dimer was measured using automated ELISA pre-operatively and at days 1 and 42 following surgery in 103 prospectively recruited patients undergoing surgery for early breast cancer(87 invasive,13 DCIS). D-dimer values were log-transformed and correlated with LN metastases, tumour size and grade and hormone receptor status using parametric statistical tests.
Results
Median age was 68 years (range 46–82). Mean tumour size was 14.6 mm (range 7.5-40). Seventy invasive cancer patients had wide local excision(WLE) and sentinel node biopsy(SNB) and 17 had mastectomy(MX) +/− axillary clearance(ANC).
Twenty-two patients had positive lymph nodes at primary surgery (MX 8,WLE 14). Of these 3(14%) were ER-ve and 19(86%) were ER+ve.
Mean pre-operative d-dimer was higher (p&lt;0.01) in LN positive (704ng/ml, 95% confidence interval, CI, 455–1088) versus LN node negative invasive cancers (443ng/ml, CI 304–627) or DCIS (366ng/ml, CI 284–471). D-dimer was also higher in patients with lymphovascular invasion (612ng/ml, CI 423–886) than in those without (454ng/ml, CI 385–534) and this approached significance (p=0.084).
Post-operative d-dimer was higher (p&lt;0.05) after MX compared to WLE at all timepoints. Following WLE + SNB for invasive cancer, post-operative d-dimer rose and was higher at day 1 and day 42 in LN positive vs LN negative and in ER negative versus ER positive cancers (see table). Repeated measures ANOVA analysis showed that the change in d-dimer over time was significantly different between subjects according to LN status (p=0.037) or ER status (p=0.015). Only one patient in the ER negative group had LN metastases. There was no association between pre or postoperative d-dimer and tumour size, tumour grade or PR status.

Conclusion
Pre-operative TP activation and the thrombotic response to surgery (as measured by d-dimer) is greater in the presence of LN metastases regardless of tumour size.
ER negative cancers (7/8 of which were LN negative) also resulted in a greater d-dimer rise, suggesting a difference in the thrombotic response to surgery between different cancer phenotypes.
Ongoing work will determine if peri-operative TP activation can act as an independent predictor of node status and cancer recurrence.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-04.
P4-09-05: CA15-3 Adds Prognostic Information in “Luminal” Type Breast Cancer – A Single Center Experience Evaluating 700 Patients with a Median Follow-Up of 5 Years.
Authors: Kantelhardt EJ , Vetter M , Steer S , Ruider T , Holzhausen H-J , Strauβ H-G , Groβe R , Thomssen C 
Published: June 2012

Abstract
Background: Prognostic markers are essential for the decision about individual therapy for patients with newly diagnosed breast cancer. Biological meaningful cancer types are revealed by gene expression analysis. Steroid hormone receptor (HR) and HER2 status of the tumor by immunohistochemistry (IHC) are more easily available and predominantly resemble these cancer types. The “luminal” type as HR pos. and HER2 neg., the “luminalHER2” type as HR pos. and HER2 pos., the “HER2” type as HR neg. and HER2 pos. and the “triple neg.” type as HER neg. and HER2 ***neg.. We evaluated preoperative serum CA 15–3 and CEA within IHC-cancer types and outcome using our own cohort from 1999–2010.
Material and Methods: Since 1999 all patients with breast cancer were entered in our tumor registry. Patients were treated by surgery and adjuvant therapy according to national guidelines (www.ago-online.de). Data was entered into SPSS by a specially trained study nurse. Follow-up was obtained yearly using our own out-patient clinic, information from general practitioners and the general cancer registry. Informed consent was taken from the patients at time of diagnosis. CA 15–3 and CEA were defined elevated if above 25 U/ml or 4,6 μg/l respectively.
Results: Preoperative serum CA15-3 available for 1149 patients. Patients with elevated results showed a reduced 5year disease-free survival (DFS) of 74.4% as compared to 84.7% (p&lt;0.001). CA15-3 remained an independent prognostic factor in multivariate analysis (nodal status, grading, HR). Within HR positive disease, normal CA15-3 values predict a significantly better 5years DFS of 89.9% compared to 79.7% (p&lt;0.001). No significant difference was seen in HR negative patients (5year DFS 57.5% vs 68.4%; p=n.s.). Patients with HER2 status available (n=700) were classified into biological tumor types by IHC. Significant differences in DFS were seen for “luminal” (n=435) tumors only (5year DFS 81.0% vs 91.8% (p&lt;0.001). Only trends of differences in DFS were seen in the other less frequent tumor types “luminalHER2” (n=90) or “triple neg.” (n=112) types. Within the “HER2” (n=63) group no discrimination by serum levels of CA15-3 was seen. CEA did not add information on prognosis.
Discussion: Decision on adjuvant therapy is increasingly based on tumor biology. Particularly, in “luminal” tumors additional prognostic information is needed to decide on adjuvant chemotherapy. CA15-3 may be an easily available, independent marker to identify patients with a higher risk of recurrence within this group. Prospective validation and comparison to molecular typing is needed.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-05.
P4-09-07: Breast Cancer Outcome by Combined Immunohistochemical ER/PR/HER2 Receptor Phenotype.
Authors: Brouckaert O , Laenen A , Reynders A , Vanderhaegen J , Amant F , Leunen K , Smeets A , Berteloot P , Van Limbergen E , Weltens C , Moerman P , Paridaens R , Wildiers H , Vergote I , Christiaens M-R , Neven P 
Published: June 2012

Abstract
Introduction: We previously reported that molecular prognostic subgroup classification of operable breast cancers resembles the classification based on combined immunohistochemical expression of ER, PR and HER-2 receptors. This update represents a larger cohort with more detailed follow-up (median 5.5y).
Patients and methods: A prospective cohort of 4334 breast-cancer patients primary operated at our institution between 2000 and 2009. Steroid receptors were considered positive for any nuclear staining, HER-2 for strong (3+) membrane staining or positive fluorescence in situ hybridization. Survival curves were calculated for six predefined breast cancer subgroups: ER + PR + HER-2 - (PPN), ER + PR - HER-2 - (PNN), ER + PR + HER-2 + (PPP), ER - PR - HER-2 - (NNN), ER - PR - HER-2 + (NNP), and ER + PR - HER-2 + (PNP) (figures not allowed in abstract). Disease free interval (DFI), distant metastatis free interval (DMFI), overall survival (OS) and breast cancer specific survival (BCSS) were calculated. A long-rank test was used for testing the null hypothesis of no difference between the groups.
Results:

Conclusion: Combined receptor expression for ER/PR/HER2 determines specific breast cancer subtypes with significant different clinical behavior. Both predictive and prognostic factors need to be considered when interpreting these results.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-07.
P4-09-13: External Validation of Adjuvant! Online Breast Cancer Prognosis Tool. Improvement Is Still Needed.
Authors: Hajage D , De Rycke Y , Bollet M , Savignoni A , Caly M , Pierga J-Y , Horlings HM , Van de VjverMJ , Vincent-Salomon A , Sigal B , Senechal C , Asselain B , Sastre X , Reyal F 
Published: June 2012

Abstract
Introduction: AdjuvantOnline is a web-based application designed to provide 10 years survival probability patients with breast cancer. Few validation studies have underlined some limitations, particularly an overestimation of the prognosis among certain subgroups of patients. Moreover, several predictors such as HER2 over expression status and proliferation markers have not been assessed in Adjuvant! original study. We provide the validation of AdjuvantOnline algorithm on two breast cancer datasets collected from two large European cancer centres, and we determined whether the accuracy of AdjuvantOnline is improved by others well known prognostic factors.
Material and Methods: The French data set is composed of 456 women with early breast cancer, treated at the Institut Curie between 1995 and 1996. The dutch data set is composed of 295 women less that 52 years treated at the Netherlands Cancer Institute between 1984 and 1995. Agreement between observation and Adjuvant! prediction was checked by testing that the calibration slope was equal to 1. Logistic models were performed to evaluate whether risk factors adds significant prognostic information, including AdjuvantOnline a priori information as an offset.
Results: Ten years survival status was known for 383 patients in the French data set and 247 patients in the Dutch data set. Adjuvant! prediction was globally well calibrated in the French data set (observed survival 86%, predicted survival 85%), but was overestimated in high grade, HER2 positive and Ki67 &gt; 20% subgroups. HER2 status, Mitotic Index, Ki67 and treatment type were strongly associated with 10-year survival, even considering AdjuvantOnline a priori information. In the Dutch data set, the overall 10-year survival was overestimated by AdjuvantOnline (observed 66%, predicted 79%), particularly in patients less than 40 years old.
Conclusion: AdjuvantOnline needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider candidates, such as Ki67, HER2 and Mitotic Index.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-13.
P4-09-15: Clinical and Pathological Predictors of Outcome among Patients with Triple Negative Breast Cancer.
Authors: Pearlstone DB , Gray M , Garofalo RM , Trapani M , Nyirenda T , Hazelwood VA 
Published: June 2012

Abstract
Background
Triple negative (TN) breast cancer portends a poor prognosis, yet outcomes remain heterogeneous. Specific characteristics of individual TN patients that can predict outcome compared to non-triple negative (NTN) patients have yet to be well defined.
Methods: A prospective oncology database at Hackensack University Medical Center was queried for all patients with invasive breast cancer between 2000 and 2005. Patients with triple negative breast cancer were identified and compared to non-triple negative patients. Numerical values were compared by Mann-Whitney test; categorical values by Chi square/Fisher exact test. Log-rank test was used to compare outcome statistics, univariate and multivariate analyses were used to identify factors affecting relapse-free survival and overall survival.
Results: A total of 2,216 patients were identified (TN: n=260; NTN: n=1956). There was no difference in race (white vs non-white; TN: 82.3% vs NTN: 87.3%) or family history of breast cancer (TN: 19.2% vs NTN: 16.8%). TN patients were significantly younger (median age; TN: 55.5 vs NTN 57.7; p&lt; .05), had larger tumors (mean cm; TN: 3.1 vs NTN: 2.4; p&lt;.05), had higher grade tumors (% grade 3; TN:74.6 vs NTN: 26.1; p&lt;.0001), had higher proliferation index (&gt;20% nuclei stained for Ki-67; TN: 30.8% vs NTN: 6.7%; p&lt;.0001), but were less likely to have lymph node metastases at presentation (TN: 35.7% vs NTN: 48.0%; p &lt; .0001). Among node negative patients, overall survival (OS) and disease free survival (DFS) were not significantly different between TN and NTN. Among node positive patients, both OS and DFS were worse for TN patients compared to NTN patients (p &lt; .0008). By univariate analysis, age, nodal status, tumor size and tumor grade were all independent predictors of DFS, but proliferation rate and TN status were not. In a multivariate analysis, however, age, TN status, nodal status and tumor size were all significantly associated with DFS.
Conclusion: Although TN patients have poor outcomes overall, among node negative patients, TN status does not affect overall nor disease free survival. Among node positive patients, however, TN status has a significant impact on outcome. In this analysis, well established predictors of outcome, including age, tumor size, tumor stage and nodal status were all independent predictors of outcome, but TN status and Ki-67 level were not.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-15.
P4-09-22: Multicenter Quality Assurance Profile Review of Lobular Breast Carcinomas Versus the 21 Gene Recurrence Score: Assessment of Clinical Relevance.
Authors: Dabbs DJ , Hicks D , Tubbs R , Bhargava R , Brufsky A 
Published: June 2012

Abstract
Introduction
The oncotype dx (ODX) 21 gene recurrence score (RS), was intended to predict the 10 year risk of breast cancer recurrence for estrogen receptor positive, lymph node negative disease (NEJM 2004;351:2817–26). The proportions of patients that were reported as low, intermediate and high risk were 51%/22%, 27%. This population of patients was dominated by ductal carcinomas (DCA), with a paucity of classical lobular carcinomas (CLCA), which are ER-rich and low grade histology. To date, there is dearth of data regarding the relationship of the RS and CLCA, and the clinical relevance regarding the ODX RS in CLCA has not been studied.
Methods
As part of quality assurance review at three institutions, the ODX RS for all CLCA were reviewed in order to determine the perceived clinical relevance of the ODX RS compared to the proportions of RS reported (NEJM 2004;351:2817–26).
Results
A total of 219 cases of ODX were performed on CLCA. The low/intermediate/high risk profile was 58%/40%/2%.
Conclusions (1) The risk profile of ODX for CLCA is very different from the original DCA dominant population previously reported. (2) If the goal of ODX is to identify candidates for chemotherapy, then a high RS is a rare event for CLCA, and as such, the judgment to administer chemotherapy to an individual patient would most likely depend upon factors other than the ODX, because 98 percent of patients are combined low/intermediate risk RS.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-22.
P4-10-09: Hormone Replacement Therapy: A Benign Breast Disease's Risk?
Authors: Hamy AS , Gronier H , Porcher R , Giacchetti S , Cuvier C , De Roquancourt A , Espie M 
Published: June 2012

Abstract
Background Use of hormone replacement therapy (HRT) has been associated with increased risk of breast cancer. However relations between use of HRT and benign breast lesions remain contradictory (1-3). Our goal was to investigate whether HRT and its duration use are associated with benign breast lesions.
Materials & Methods From 2001 to 2007, 2708 patients with a non palpable breast lesion were referred to our breast care center. Radiological abnormalities were screened either by breast ultrasound mammography, or MRI. Of those, 1 329 patients had a biopsy in our Radiology Unit. We focus on the postmenopausal women (n=739). Clinical data including HRT use extent were reported. Patients with previous history of benign breast disease or malignancy were excluded.
Results The analysis was performed on 739 patients. Biopsies yielded a benign result in 414 (56%) of them (fibroadenoma n=71, blunt duct adenosis n=94, fibrocystic disease n=92, epithelial hyperplasia n=56, others n=101), high risk lesions in 57 (8%) (atypical ductal hyperplasia n=28, atypical lobular hyperplasia n=19, lobular carcinoma in situ n=10) and malignancy in 268 (36%) (not studied here). For the 471 patients with benign or high risk breast lesion, the median age was 59 years, 80% had at least one pregnancy and 27% had a family history of breast cancer. Among these 471 patients, 47% of them had used an oral contraceptive and 53% of them a HRT, with a mean duration of use of 2 years.
The HRT use was not significantly associated with the type of benign or high risk breast disease. No association was observed either between breast disease and duration of HRT (less or more than 7 years respectively).Older age was significantly correlated to atypia or carcinoma (median age at diagnosis 59 y.o in benign lesions, 60 y.o in high risk lesions and 62 y.o in malign lesions, with significant difference) (p&lt;0,0001).

Conclusion In this study of postmenopausal women, HRT and its duration use were not associated with the type of benign or high risk breast lesion. Although a lack of statistical power may be invoked to explain the results, we are called to believe that the magnitude of an effect of HRT use is small, if ever it exists.
1. Finkelde DT, Kitchen PR, Hayes PR, McKinlay MR, Henderson MA 2001 Symptomatic benign breast disease and hormone replacement therapy. Breast 10:127–130
2. Gayet A, Esteve J, Seradour B, Piana L, Jacquemier J 2003 Does hormone replacement therapy increase the frequency of breast atypical hyperplasia in postmenopausal women? Results from the Bouches du Rhone district screening campaign. Eur J Cancer 39:1738–1745
3. Rohan TE, Miller AB 1999 Hormone replacement therapy and risk of benign proliferative epithelial disorders of the breast. Eur J Cancer Prev 8:123–130
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-09.