bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating tumor cells in operable breast cancer: a pilot study.
Authors: Sandri MT , Zorzino L , Munzone E , Cassatella C , Luini A , Bassi F , Salvatici M , Botteri E , Rotmensz N , Esposito A , Adamoli L , Goldhirsch A , Nolè F 
Published: December 2010

Abstract
Abstract #5028
Background. Circulating tumor cells (CTCs) in the peripheral blood are an ideal source for the detection of disseminated tumor cells because of an easy sampling procedure. Their prognostic significance has been demonstrated in metastatic breast cancer, while little data exist in operable patients. Aims of this study are the evaluation of the prevalence and kinetics of CTCs before and after surgical treatment and the possible correlation between CTCs and clinico-pathological characteristics and biological features. Methods. We analyzed 30 ml of peripheral blood from 60 T1-T3, any N, M0 breast cancer pts, before surgery and after 5 days. In case of positivity of one of the perioperative samples, a further sample was taken after 30 days. The presence of CTCs was assessed with the CellSearch System (Veridex, USA). Samples were subjected to immunomagnetic enrichment with an anti-Epcam-antibody: CTCs were defined as nucleated cells expressing cytokeratin 8, 18 and 19 but lacking CD45. A sample was considered positive when 1 or more cells were detected. Results. Data are available for 50 pts. We found ≥1 CTC in 28% of the pts (n=14/50) before surgery, and in 29% of the patients (n= 12/42 ) at 5 days. The median number of CTCs was 1, with a range of 1-3. We found a borderline significant association between the presence of CTCs at baseline and the presence of vascular invasion (p=0.09). The presence of CTCs at baseline did not correlate with tumor size (p=0.66), grading (p=0.88), presence of estrogens receptor (p=0.30), presence of progesteron receptor (p=0.30), HER2/neu status of the tumor (p=1.0), or with the presence of lymph node metastases (p=0.71). In 42 pts we have the data of CTCs determined at baseline and at day 5: 27 patients showed concordant results (23 negative and 4 positive). Among the 15 patients with different results, 8 were negative at baseline and positive at day 5: 6 out of the 8 patients had positive nodes. At day 30 we analyzed samples from 18 subjects: persistence of at least 1 CTC was found in 18 % of patients (n=5). Conclusions. The results of this explorative study are very preliminary and a larger number of patients and a long-term follow-up will be required. However, it is of interest the borderline correlation between presence of CTCs at baseline and vascular invasion, and between appearance of CTCs and nodal involvement in postoperative samples. The study is ongoing and the patients will be followed during and after adjuvant treatment to explore the prognostic significance of persistency of CTCs. Complete data will be presented.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5028.
Behaviour and metastatic potential of her2/neu positive and her2/neu negative circulating epithelial tumor cells (CETC) during adjuvant systemic therapy in breast cancer.
Authors: Camara O , Hammer U , Gajda M , Kroll T , Krauspe S , Gellner A , Joerke C , Runnebaum IB , Hoeffken K , Pachmann K 
Published: December 2010

Abstract
Abstract #5030
Background: Most tumor patients do not die from the primary tumor but from metastases in vital organs. Here we report on the influence of adjuvant chemotherapy and trastuzumab on the remnant CETC patients with her2/ positive tumors after surgery and the impact on metastasis formation.&#x2028; Material and Methods: Tumor cells were quantified with an automated microscope (Laser Scanning Cytometer®, Icis or ScanR) from anticoagulated blood drawn before each new therapy cycle from patients treated with systemic chemotherapy after surgery and subsequent maintenance therapy with trastuzumab. After red blood cell lysis leucocytes were stained with PE-anti-CD45 and tumor cells with FITC-anti-EpCAM. FISH analysis was performed for determination of the proportion of her2/neu positive cells and changes registered as % increase or decrease. The response to therapy was correlated to outcome.&#x2028; Results: Almost all her2/neu positive breast cancer patients scheduled for systemic treatment had CETC before therapy. A decrease in cell numbers highly correlated with relapse free survival. Her2/neu positive patients responding to therapy with an increase in CETC were at increased risk to develop further increasing cell numbers also during subsequent trastuzumab treatment. Her2/neu positive patients who did never receive trastuzumab all had increasing CETC numbers during the postoperative observation time and all have suffered relapse. Patients who received trastuzumab only after adjuvant treatment all had decreasing CETC numbers and all are in sustained complete remission after up to 4 years. Of the patients who received trastuzumab together with adjuvant treatment those who showed no change or an increase in CETC in spite of trastuzumab had increasing proportions of FISH high amplified cells and a higher risk of relapse than patients with decreasing CETC during trastuzumab.&#x2028; Discussion: Monitoring CETC will not only provide the earliest and most reliable indicator of successful adjuvant treatment and spare patients unnecessary treatment but also patients with the highly aggressive her2/neu positive tumors can be discerned into such with high and low risk of relapse even during trastuzumab therapy. This warrants further therapy studies to control what patients may benefit from addition of e.g. small molecules already during therapy before development of metastases.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5030.
Abundance and distribution of polychlorinated biphenyls (PCBs) in breast tissue.
Authors: Ellsworth DL , Gillard D , Love B , Ellsworth RE , Deyarmin B , Hooke JA , Kostyniak PJ , Shriver CD 
Published: December 2010

Abstract
Abstract #5039
Background: Breast cancer is a complex disease whose causative factors remain ambiguous and poorly defined. Many environmental chemicals accumulate in human tissues and may contribute to breast cancer risk. Polychlorinated biphenyls (PCBs), which constitute a class of chlorinated compounds that are ubiquitous in the environment, are believed to be associated with adverse health effects. Because the rising incidence of breast cancer may result from exposure to increasing levels of exogenous chemicals, there is keen interest in determining relationships between exposure to environmental chemicals and breast cancer risk.&#x2028; Material and Methods: Frozen sections of breast tissue were collected from each quadrant and the central region of the breast from 47 patients enrolled in the Clinical Breast Care Project at Walter Reed Army Medical Center. Pathological diagnoses ranged from disease free prophylactic mastectomy to metastatic breast cancer. From a portion of each sample, 98 PCB congeners were assayed by pressurized liquid extraction followed by high resolution gas chromatography.&#x2028; Results: PCBs were abundant in breast tissues. Only one congener was not observed in any patient and four (153, 138+163, 180, 206) were seen in all patients in at least one quadrant. Mean total PCB concentration in 202 breast quadrants was 602 ng/g lipid (range 0-4030), while for individual congeners, PCB 153 had an average level of 107 ng/g lipid (range 8-773 ng/g). Total PCB concentration (P&lt;&lt;0.001) and presence of 26 congeners (P&lt;0.05) were highly correlated with patient age, particularly in the UIQ and LOQ, but not in the central region, suggesting that chemicals may accumulate at different rates in different regions of the breast. Similarly, no significant differences were observed for PCB concentrations among the four traditional quadrants, but 23 PCBs were present at significantly lower levels (P&lt;0.05) in the central region. When examining PCB levels by disease status, seven individual congeners and median overall levels were significantly higher (P&lt;0.05) in patients with invasive cancer compared to disease free patients.&#x2028; Discussion: Population monitoring is beginning to assess exposures of the general public to environmental chemicals to evaluate long-term health effects. This study showed that many PCB residues are present in human breast tissue, these chemicals are not distributed evenly, and several are correlated with age and presence of invasive disease. Improved understanding of the true carcinogenic potential of environmental chemicals may be useful in efforts to reduce individual risk for breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5039.
Promoter hypermethylation is an early event in breast carcinogenesis.
Authors: Park M , Yoon J , Lee J , Choi M , Yoon H , Jung S , Lee B , Fackler M , Sukumar S 
Published: December 2010

Abstract
Abstract #5041
Background. Aberrant methylation of CpG islands in the promoter region of tumor suppressor genes has become established as an important epigenetic mechanism for gene silencing. Promoter hypermethyaltion in precursor lesions at risk for progression to invasive cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. In breast cancer promoter hypermethylation has been described for several genes covering all aspects of cellular function. However, the methylation studies of precursor lesion of the breast are rather sparse and mostly done in a purely qualitative manner.&#x2028; Design. To evaluate the significance of alterations in promoter hypermethylation during multistage carcinogenesis of the breast, quantitative multiplex methylation-specific PCR of six genes (APC1, Cyclin D2, HIN-1, RAR-b, RASSF1A, and Twist) was performed on DNA from 15 normal breast tissues, 21 usual ductal hyperplasia (UDH), 48 ductal carcinoma in situ (DCIS), and 35 stage I invasive ductal carcinoma (IDC), not otherwise specified.&#x2028; Results. We found no to very low levels of promoter methylation in normal samples. In general UDH, DCIS, and IDC samples revealed varying levels of methylation ranging from 0 to 100%. One-way analysis of variance showed that the methylation levels of all six genes increased significantly with the progression of breast neoplasia from normal epithelium, through hyperplasia, to DCIS. However, methylation levels were not significantly different between DCIS and IDC.&#x2028; Conclusion. Our results suggest that promoter hypermethylation is an early event in breast carcinogenesis. Promoter hypermethylation in the precursor lesions of the breast cancer may be used as a target for cancer chemoprevention.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5041.
GSTP1 promoter hypermethylation during breast cancer development.
Authors: Park M , Yoon J , Lee J , Choi M , Youn H , Jung S 
Published: December 2010

Abstract
Abstract #5042
Background. Promoter hypermethylation in precursor lesions of the breast cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. GSTP1 is inactivated by promotor hypermethylation in invasive breast cancers. However, little is known about epigenetic silencing of GSTP1 gene by promoter hypermethylation in precursor lesions.&#x2028; Method. To determine the significance of GSTP1 promoter hypermethylation in breast carcinogenesis, methylation status of GSTP1 gene was studied by nested methylation-specific PCR and GSTP1 expression was studied by immunohistochemistry in invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), usual ductal hyperplasia (UDH) and normal breast tissue.&#x2028; Results. GSTP1 promoter hypermethylation was detected in 4/24 (16.7%) of UDH, 18/49 (36.7%) of DCIS, and 14/36 (38.9%) of IDC. No hypermethylation was detected in normal breast tissues. GSTP1 promoter hypermethylation was found to be progressively elevated during breast carcinogenesis (P &lt; 0.01). GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (P &lt; 0.01 for UDH, P &lt; 0.001 for DCIS and IDC).&#x2028; Conclusion. Our results suggest that GSTP1 promoter hypermethylation is an early event in breast carcinogenesis and appears to functionally silence GSTP1 expression. GSTP1 promoter hypermethylation in the precursor lesions of breast cancer may be used as a target for cancer chemoprevention.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5042.
Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers in the Netherlands.
Authors: Pijpe A , Manders P ,   the Netherlands Collaborative Group on Hereditary Breast Cancer (HEBON), van Leeuwen FE , Rookus MA 
Published: December 2010

Abstract
Abstract #505
Background: Physical activity reduces the risk of breast cancer in the general population by 20-40%. Suggested biological mechanisms include a reduction of adipose tissue and decreased lifetime exposure to estrogens. This is one of the first studies that investigates the association between physical activity and breast cancer risk in BRCA1/2 mutation carriers (carriers).&#x2028; Patients and methods: We analyzed data from a nationwide retrospective cohort study (GEO-HEBON), including 1026 carriers, of which 465 had a history of breast cancer. We examined the association between breast cancer risk and average (METhr/wk) sports, walking/cycling, occupational, household, and total physical activity, lifetime and for age-periods below and above age 20, separately. All analyses were stratified for birth cohort and gene, clustered on family, and adjusted for confounders and other physical activity variables (when investigating separate components).&#x2028; Preliminary results: For adulthood sports activity we found a risk reduction for active carriers (low: Hazard Ratio (HR) = 0.72; 95% CI = 0.54-0.96; medium: HR = 0.64; 95% CI = 0.46-0.90; high: HR = 0.71; 95% CI = 0.48-1.06) when compared to carriers who had never engaged in sports. No risk change was found for sports activity before age 20. For lifetime (mainly adulthood) household activity we found a risk reduction of 0.74 (95% CI = 0.57-0.96) for the second versus the lowest quartile but for higher quartiles HRs were not significantly decreased, and a similar pattern for occupational activity (0.53 (0.35-0.82)). We found neither an effect for walking/cycling activity nor for total physical activity.&#x2028; Discussion: Our physical activity information was relatively extensive, and we used proxy-questionnaires to examine survival bias. Limitations include the retrospective character of the cohort and potential misclassification bias. In conclusion, these preliminary results suggest that physical activity may reduce the risk of breast cancer in carriers. The inverse associations were clearest for physical activity during adulthood. Time-dependent, weighted (for testing bias), and stratified (for example by menopausal status and Body Mass Index) analyses will be conducted.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 505.
Do stem cell markers have significant implication in breast cancer? Immunohistochemical study for CD44 and CD24.
Authors: Kim H , Kim M , Ahn S , Son B , Kim S , Jung K , Ahn J , Kim H , Gong G 
Published: December 2010

Abstract
Abstract #5058
Background: We reported that breast cancer expressing CD44+CD24-/low showed a favorable prognosis in contrary to the in vitro/in vivo studies. We further followed this data up to 99 months and analyzed it according to CD44 expression, CD24 expression and hormone expression.&#x2028; Design: immunohistochemical stainings for CD44s and CD24 as well as prognostic markers including estrogen receptor, progesterone receptor, p53, and Her2/neu were done using tissue microarray blocks containing 645 consecutive cases of invasive breast carcinomas from 1993 to 1998. Mean follow up periods were 99.5 months. Cases were categorized into four subgroups (CD44-/CD24+, CD44+/CD24+, CD44-/CD24-, CD44+/CD24-) based on the immunohistochemical staining results and compared them with clinicopathologic parameters. Immunostainings for CD44s and CD24 interpreted as positive if at least 1% of tumor cells show distinct membranous and/or cytoplasmic stainings. In the positive group of CD24, we categorized it as three subgroups according to the degree of positivity.&#x2028; Results: CD44+CD24-/low group showed inversely associated with lymph node metastasis and the tumor stage than other subgroups (p=0.001 and p=0.018, respectively). And CD44+CD24-/low group was showed an increase in disease free survival and overall survival (p=0.003, p=0.002) In the subgroup analysis of CD24 expression (0, grade 1, grade 2, grade 3), the incidence of metastasis and death was more frequently observed in the cases with the higher expression of CD24. (DFS: p=0.03, OS: p=0.001). With respect to the CD44, CD44- group showed frequent metastasis and death (p=0.01, both) however, for the receptor positive groups, not CD44 but CD24 expression resulted negatively to the overall survival significantly(p=0.01, Relative risk=1.90) on multivariate analysis. For the receptor negative groups, especially triple negative group, lack of CD44 expression made overall decreased to 50%(p=0.03, hazard ratio=0.5)&#x2028; Conclusion: In contrast to cell line studies, CD44+CD24-/low phenotype is considered a favorable prognostic subgroup of breast cancer associated with less frequent nodal metastasis, lower tumor stage and infrequent distant metastasis. For receptor positive breast caner, CD24 expression effect DFS, OS significantly, and For receptor negative group, especially triple negative breast cancer, Lack of CD44 expression made and effect OS inversely.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5058.
Aberrant inducible nitric oxide synthase expression predicts poor survival in estrogen receptor negative breast cancer, and is associated with a gene expression signature similar to that of basal-like breast cancer.
Authors: Glynn SA , Boersma BJ , Howe TM , Ridnour L , Wink D , Yi M , Yvantis H , Ambs S 
Published: December 2010

Abstract
Abstract #5067
Background: Inducible nitric oxide synthase (iNOS) is a key enzyme in the inflammatory process, that catalyses the production nitric oxide (NO). NO is a free radical that affects the redox state of tumor cells and thus cell signaling. We hypothesized that iNOS expression is associated with markers of outcome and influences breast cancer survival by estrogen receptor (ER) α-independent mechanisms.&#x2028; Method: 248 cases of incident breast cancer were examined by IHC for iNOS expression. Univariate and multivariate analyses were performed to assess correlations between iNOS expression and clinico-pathological features of breast cancer, and patient survival. In addition, 35 tumors were laser capture microdissected and the effect of iNOS on gene expression profiles analyzed by Affymetrix gene expression arrays.&#x2028; Results: iNOS was moderately to strongly expressed in the majority of breast tumors (70%). iNOS was significantly associated markers of poor prognosis including p53 mutation accumulation, increased microvessel density, and high tumor grade. iNOS was not associated with race/ethnicity (143 African American, 105 Caucasian). In Cox regression analysis, high levels of iNOS expression was a predictor of both 5-year (Hazard Ratio - 5.41; 95% C.I. 1.25 to 23.48) and 10-year (H.R. 4.63; 95% C.I. 1.36 to 15.73) breast cancer-specific survival in women with ER-negative tumors. iNOS was not a predictor of ER positive breast cancer survival. Neither tumor p53 status nor chemotherapy modified these associations. Gene expression analysis identified changes in significant changes in gene expression with high levels of iNOS expression in ER negative breast cancer. This observation was not seen in ER positive breast cancer.&#x2028; 44% of the iNOS associated genes had previously been found to be associated with the ER negative breast cancer subtype, basal-like breast cancer phenotype.&#x2028; Discussion: These results suggest that iNOS contributes to the pathogenicity of ER-negative breast cancers and is a predictor of patient survival. The similarity of the iNOS induced gene signature to that of basal-like breast cancer, suggests that iNOS may play a role in the aggressive nature of basal-like breast cancer and may be a potential therapeutic target for the treatment of ER negative and basal-like breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5067.
Genomic score predictive of metastatic evolution in breast cancer.
Authors: MacGrogan G , Guedj M , Primois C , Brouste V , Banneau G , Debled M , Mauriac L , Sevenet N , Petel F , Longy M , Bonnet F 
Published: December 2010

Abstract
Abstract #5069
Background: Despite of the existence of clinical and pathological prognostic factors, the metastatic evolution in breast cancer remains uncertain in a substantial proportion of cases. Previous studies have suggested that genome profiling could address this question. In this context we developed a genomic score to evaluate the total level of copy number aberrations in a given tumor, based on data from array-CGH analysis.&#x2028; Material and Methods:We performed array-CGH analysis in a series of 135 sporadic, operable breast cancers treated at our institution between 1989 and 1992 (more than 10 years follow-up). These cases included 45 invasive ductal carcinomas with metastatic evolution (M+) and 90 cases that did not relapse at 11 years (M- ). Cases were paired on patients age and initial axillary lymph node status (pN +/pN0), and were equally distributed between the two groups of evolution: 25 pN0/M+, 20 pN+/M+, 50 pN0/M- and 40 pN+/M-. Tumoral DNA was co-hybridized with pooled normal germline DNA from 20 individuals on a 4407 BAC-array (CIT-V6) provided by the CIT program and manufactured by Integragen. Gain, normal and loss status (GNL) were generated from the CapWeb pipeline developped by the bioinformatics plateforme from Institut Curie (Paris). Clinical, pathological and genomic data were retrieved through Annotator, the CIT cancer database and the analysis has been driven by using the R statistical software along with the CIT R packages.&#x2028; Results:The proposed score of genomic instability is based on two items: (i) the proportion of alteration and (ii) the number of altered genomic regions. By applying a set of appropriate thresholds on these two items we were able to define three highly different prognostic subgroups, 95 % (18/19), 74 % (65/88) and 25 % (7/28) 11 years metastatic-free survival respectively (p-value = 4.04e−10) while univariate analysis of histological parameters such as tumor size and SBR grade showed weaker associations (p-values of 0.006 and 0.065 respectively). The predictive properties of the genomic score have been assessed by cross-validation but also on other independent large data sets. A signature of genome instability inferred from genomic and gene expression profiles will also be proposed.&#x2028; Conclusion: Genomic profiling in breast carcinoma is a strong tool for prognostication in breast cancer. We developed a computational method to characterize genome instability of that predict clinical outcome in breast cancer and could be useful for more accurate therapeutic choice but also for identifying new therapeutical targets.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5069.