bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relevance of Traditional CEA and CA15-3 and Bone Turnover Markers in Predicting Bone Relapse in Breast Cancer Patients.
Authors: Ibrahim T. , Sacanna E. , Mercatali L. , Scarpi E. , Ricci M. , Ricci R. , Serra P. , Tison C. , Amadori D. 
Published: December 2010

Abstract
Background: Over 50% of breast cancer patients who relapse systemically develop bone metastases. The RANK/RANKL/OPG axis governs osteoclastogenesis and bone reabsorption. In particular, osteoprotegerin (OPG) is a decoy receptor of RANK-L (receptor activator of nuclear factor kappa B ligand) and seems to prevent bone destruction by blocking the binding of RANKL with its receptor. We studied the efficacy of circulating OPG compared to the traditional markers CEA and CA15-3 for the early detection of bone lesions.Methods: The study was carried out on peripheral blood from 72 patients with breast cancer, of whom 33 were disease-free and 39 had bone metastases. The OPG transcript was determined using quantitative PCR analysis, and the traditional markers were quantified by immunoenzymatic assays.Results: The OPG median value was higher in disease-free patients (median = 1.7, 0.4-8.9) than in bone-relapse patients (median = 0.6, 0.1-5.2) (p&lt;0.001). CEA and CA15-3 median values were 1.3 (0.0-8.3) ng/ml and 10.6 (0-45.7) U/ml, respectively, in disease-free patients and 4.8 (0.0-90.6) ng/ml and 69.8 (7-1538) U/ml, respectively, in patients with bone metastases (p&lt; 0.0001 for both markers). Considering 0.9 as cut off of OPG relative expression, our analyses revealed a specificity of 88% with respect to 97% for CEA and 94% for CA15-3. OPG sensitivity was 73% compared to only 49% for CEA and 67% for CA15-3. When OPG was considered in combination with the traditional markers, sensitivity increased from 49% to 83% for CEA and from 67% to 88% for CA15.3.Conclusions: Our results on a preliminary series of breast cancer patients indicate that the bone turnover marker OPG greatly increases CEA and CA15-3 sensitivity in predicting bone metastases.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3027.
Prospective Evaluation of Serum HER2 and HER2 Expression on Circulating Tumor Cells in Patients with Metastatic Breast Cancer within the DETECT Study.
Authors: Mueller V. , Riethdorf S. , Rack B. , Janni W. , Fasching P. , Pantel K. , Gebauser G. , Solomayer E. , Aktas B. , Kasemier-Bauer S. , Fehm T. 
Published: December 2010

Abstract
Background: Assessment of HER2 status at the time of metastatic disease might help to optimize treatment decisions in patients with no HER2 status determined at first diagnosis and could also be helpful since HER2 status may change during disease progression. In this context, determination of serum HER2 or the evaluation of HER2 status on circulating tumor cells (CTC) is of potential relevance especially for optimizing HER2-directed therapy. The aim of this study was therefore to determine the serum HER2 status and the HER2 status of CTC from corresponding patients.Methods: Blood samples were obtained in a prospective multicenter setting from 251 patients with metastatic breast cancer at the time of disease progression. Serum HER2 was determined using the commercial HER2 ELISA-kit (Oncogene Science). CTC were detected and HER2 expression was assessed with the CellSearch™ system (Veridex).Results: 119 of 251 (47%) metastatic patients had elevated serum HER2 levels above 15 ng/mL. Serum HER2 was elevated in 49 (66%) of 74 patients with HER2 positive primary tumors, in 57 of 148 (39%) with HER2 negative primary tumors and in 13 of 29 (45%) patients with unknown HER2 primary tumor status. CTC were detected in 133 of 243 evaluable patients (5 or more cells), in these HER2 overexpression on CTC (strong overexpression in at least one cell) was detected in 52 cases (39%). Only 20 of these patients had a HER2 positive primary tumor. In patients with HER2 positive CTC, serum levels were above the cut off in 34 of 52 (65%), while in those with HER2 negative CTC 44 of 81 (54%) showed elevated HER2 serum levels. Concordance between HER2 status of circulating tumor cells and elevated serum HER2 was seen in 71 of 133 patients (53%).Conclusions: Our study demonstrates with a prospective design that also in patients with initially negative HER2 tumor status elevated serum HER2 levels and/or HER2 positive CTC can be detected at the time of metastatic disease. This is of clinical relevance since these patients in current practice do not have access to HER2 targeted therapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3050.
Amplification of mRNA from Formalin-Fixed Paraffin-Embedded (FFPE) Breast Cancer Tissues without 3' Bias and Multiplex Expression Analysis on Flow-Through Microarrays.
Authors: Englert D. , Wilson D. , Laken S. 
Published: December 2010

Abstract
Background: FFPE samples are an abundant sample resource for validation of expression-based assays and are will suited for routine clinical testing. Analysis on microarrays enables the analysis of many transcripts from small samples. However, mRNA in FFPE sections is degraded and cross-linked, with RNA fragment sizes of a few hundred bases or less, and consequently standard methods of microarray sample preparation are not reliable unless probes are very strongly biased to the 3' end. It is not always possible to design high quality probes within this restricted region of mRNAs. Amplification of target sequences any place within transcripts would permit greater flexibility in probe design and optimization of probe sets for reliable multiplex analysis.Material and Methods: Total RNA extracted from FFPE samples was subjected to two rounds of amplification with the ExpressArt TRinucleotide kit (AmpTec), which preferentially primes cDNA synthesis near the 3'-ends of mRNAs (rather than at poly-A sites) and selects for mRNAs against ribosomal RNAs. Biotin-labeled anti-sense RNA (aRNA) was prepared from the second round cDNA with the Illumina® TotalPrep™ RNA kit (Applied Biosystems). The labeled aRNA was hybridized to probes immobilized in singlet on flow-through microarrays on the Ziplex Automated Workstation (Xceed Molecular). Performance was assessed by the analysis of titration mixtures prepared from mRNA from breast cancer and colon cancer FFPE tissue blocks.Results: Median CVs of technical replicates were less than 25%. Linear responses were observed in the analysis of the titration mixtures, and all correlations between predicted and observed expression values of the titration mixtures had R2 values greater than 0.8. The data indicated that the minimum detectable expression difference was less than two-fold. Similar signal intensities were observed for 3'-biased probes and probes several hundred bases from the 3'end, confirming the lack of 3' bias in the amplification.Discussion: The results demonstrate the feasibility of amplifying and quantifying sequences at any position within transcripts in degraded mRNA from FFPE samples. Expression differences of less than two-fold may be analyzed with tens or hundreds of probes for translational research and clinical assay development on the Ziplex Workstation. Many probes may be tested in parallel to optimize probe sets for specific tests.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3052.
Genetic Polymorphisms in EGFR Gene: No Evidence for an Association with the Risk of Breast Cancer.
Authors: Gorlov I. , Gorlova O. , Jupe E. 
Published: December 2010

Abstract
EGFR expression is an important predictor of prognosis for breast cancer. An association of the EGFR expression breast tumor with the prognosis suggest that germline polymorphisms in the gene also may be associated with the risk of breast cancer. The published studies on the association of the genetic polymorphisms in the EGFR gene are conflicting.We genotyped 15 SNPs in the EGFR gene region: rs11506105, rs11543848, rs12674036, rs1558544, rs2072454, rs2075109, rs4947986, rs6965469, rs6969537, rs759171, rs7801956, rs4947963, rs747322, rs17172451, and rs1554718 in 500 Caucasian breast cancer patients and 500 matched controls to assess the association of the SNPs with the risk of breast cancer. SNPs were selected based on the LD pattern in the region and how close they are located to exons and promoter. Additionally we analyzed an extremely polymorphic CA repeat (rs11568315) located in the regulatory region of the gene. This polymorphic repeat has 11 alleles (alleles were defined by the number of the CA repeats, 14-23).We conducted pooled analysis and also stratified subjects by menopausal status. We have not found any significant association of the polymorphism with breast cancer risk. We were not able to confirm the previous finding that the increased number of the CA repeats in the rs11568315 was associated with elevated breast cancer risk. In conclusion, despite the fact that the expression of EGFR in breast cancer is an important predictor of progression, we found no evidence that germline polymorphisms in the gene are associated with the increased risk of breast cancer. The study was supported by 1R03CA128025-01A1 grant.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3060.
Differences in Breast Cancer Subtypes among Asian-American Women with Invasive Breast Cancer in New York City.
Authors: McCarville K. , Flam A. , Forst M. , Swistel A. , Osborne M. , Moore A. , Vahdat L. , Klein P. , Christos P. , Mazumdar M. , Chuang E. 
Published: December 2010

Abstract
Background: Specific breast cancer (BC) subtypes conferring distinct phenotypic and prognostic outcomes have been defined by molecular gene expression arrays. A recent study suggested that differences in BC subtypes exist among ethnic subgroups of Asian women in California. It has also been reported that there are differences in clinical outcomes among Asians with BC in the US, with Filipinos having a worse prognosis compared with other Asians. We sought to determine whether differences in BC subtypes exist among Asians in New York.Methods: Using outpatient registration records from Weill Cornell Breast Center and St. Vincent's Medical Center in New York City, we identified patients who were diagnosed with stage I, II, or III invasive BC between 1997 and 2007 who were of Chinese, Filipino, Japanese or Korean ethnicity. We reviewed pathology records according to an IRB approved protocol and recorded patient data for age, stage, grade, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2/neu at diagnosis. Immunohistochemical surrogates for the four molecularly defined breast cancer subtypes were used according to accepted definitions (Luminal A: ER+Her2-; Luminal B: ER+ Her2+; Her2/neu: Her2+ ER-; Basal-like: ER-PR-, Her2-) Using chi-square analysis, we explored the relationship between ethnicity and BC subtypes.Results: 346 Asian women were identified with invasive breast cancer. Among the Chinese subgroup, 67% were of the Luminal A subtype, 15.3% were Luminal B, 10% were the Her2/neu subtype and 8.5% were Basal-like. Filipinos had a higher proportion of Luminal B cancers compared to the other ethnic groups. Filipinos and Koreans had a higher proportion of the Her2+/ER- subtype compared to Chinese and Japanese (P=0.004 by chi-square test). When considering all Her2/neu positive cancers, Filipinos had a significantly higher proportion of HER-2/neu positivity (46%) compared to Chinese (25%), Japanese (14%) and Korean (29%) groups (P=0.002). Filipinos and Koreans had a higher proportion of ER negative cancers and Grade III cancers compared to Chinese and Japanese (P=0.001 for ER status and P=0.01 for grade). In our series, Korean subjects were significantly younger than the other three ethnic groups (P&lt;0.0001 by AVOVA test).Conclusions: Differences in BC subtypes exist among Asian women with invasive breast cancer in New York. Filipino women are significantly more likely to have HER-2/neu positive BC compared with Chinese, Japanese, and Korean women. Our results are supportive of results from a study in which differences in distribution of Her2/neu positive cancers among Asians in California were seen. Furthermore, these findings provide one explanation for the worse clinical outcome for Filipinos compared with other Asians that has been previously reported.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3067.
Prognostic Value of Lymphogenic Micrometastasis of Patients with Breast Carcinoma: A Multicenter Cohort Study.
Authors: Gobardhan P. , Madsen E. , Elias S. , van Wely B. , van den Wildenberg F. , Theunissen E. , Ernst M. , van der Pol C. , Borel Rinkes I. , Wijsman J. , Vles W. , de Hooge P. , Ruitenberg H. , Perre C. , van Dalen T. 
Published: December 2010

Abstract
Introduction: Since the introduction of sentinel lymph node biopsy (SLNB) for staging breast cancer, lymphogenic micrometastases are commonly detected. The prognostic meaning of these small lymph node metastases and the consequences regarding the indication for adjuvant systemic treatment is under debate. Currently, robust data with a long time follow up are lacking.Method: Between January 2000 and December 2002 1411 patients with a cT1-2N0 breast carcinoma underwent surgery in seven hospitals in the Netherlands. Pathological examination of the sentinel node consisted of serial sectioning of SLN's and H&E and IHC staining. Based on the presence of lymph node metastases patients where divided into four groups: pN0 (n = 922), pN1micro (n = 103), pN1a (n = 285) and pN≥1b (n = 101). Median follow up was 77 months.Results: At the end of follow-up 184 (13.0%) patients had died. Breast cancer recurred in 244 (17.3%) patients, 165 of them having distant metastases (11.7%) patients. The 5- years overall survival was 93% for patients with pN0 disease, 94% for pN1micro, 88% for pN1a and 78% for pN≥1b (p &lt; 0.001). The 5-years disease free survival was 87%, 90%, 85% and 72% (p &lt; 0.001) respectively.Following adjustment for possible confounding characteristics and for adjuvant systemic treatment, overall survival was similar for pN0 en pN1micro patients and significantly worse for pN1a and pN≥1b (HR 1.18; 95% CI 0.58-2.39, HR 2.47; 95% CI 1.69-3.63, HR 4.36; 95% CI 2.70-7.04 respectively). Disease free survival was similar too in the pN0 and pN1micro group, and worse for pN1a and pN≥1b (HR 0.96; 95% CI 0.56-1.67 vs. HR 1.64; 95% CI 1.19-2.27, HR 2.95; CI 1.98-4.42). Distant metastases were more commonly observed in the pN1micro group than in the pN0 group (HR 1.22; 95% CI 0.60-2.49), but not significantly and far less than in the pN1a and pN≥1b group (HR 2.26; 95% CI 1.49-3.40, HR 3.49; 95% CI 2.12-5.77).Conclusion: After a relative long time of follow up disease free and overall survival for patients with micrometastasis in SLNs is comparable to patients without lymphogenic metastasis and more favourable than patients with macrometastasis. The presence of micrometastatic disease in the SLN is in itself not an indication for adjuvant systemic therapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 307.
EGFR Gene Copy Number and Response to Lapatinib/Capecitabine in HER2 Positive Metastatic Breast Cancer Patients Pretreated with Trastuzumab.
Authors: Fabi A. , Graziano V. , Merola R. , Metro G. , Papaldo P. , Cianciulli A. , Mottolese M. , Sperduti I. , Vico E. , Cognetti F. 
Published: December 2010

Abstract
Background: Lapatinib (L) is a potent and selective dual inhibitor of EGFR and HER2. In HER2 positive metastatic breast cancer (MBC) pretreated with trastuzumab-based therapies, the association of L + Capecitabine (C) showed superior response rate (RR) and progression free survival (PFS) over C alone. We analyzed the correlation between EGFR gene copy number and clinical outcome in a population undergoing treatment with L 1250 mg daily plus C 2000 mg/m2 days 1-14 every 21. Materials and methods: EGFR gene copy number was assessed by FISH analysis in paraffin-embedded tissue blocks from 30 HER2 positive patients who had failed at least one trastuzumab-based therapy in the metastatic setting. EGFR gene status was scored as: the mean value of EGFR gene copy number (GCN) per nucleus, the mean ratio between EGFR and Chromosome 7 and the percentage of cells displaying more than 5 EGFR GCN. A receiver operating characteristic (ROC) analysis was set up to define the cut-off of mean EGFR GCN. A value greater than 3.36 was able to discriminate responders versus non-responders. The primary end point of the study was identification of the EGFR FISH score that best predicts RR Results: Twenty-five patients were evaluable for EGFR FISH analysis. No sample displayed a homogeneous amplification of the EGFR gene by ratio (EGFR gene/CEP 7 ≥2). Patients characteristics were as follows: median age 52.4 (range 32-70), visceral disease in 20 patients (80%), brain metastases in 11 patients; median number of previous trastuzumab-based therapies was 2 (1-4). Twelve patients achieved a partial response for a RR of 48% (95% CI: 28.8-64.5). At a median follow up of, PFS was 7 months (95%CI: 5-8). Median overall survival has not been reached at the time of analysis. Mean EGFR GCN was &gt; 3.36 in 10/25 patients. These patients showed a significantly higher RR (n=8/10; 80%) as compared to those with mean EGFR GCN ≤3.36 (n= 4/15; 27%), (p=0.009). No significant difference in terms of PFS was seen. Conclusion: high EGFR GCN might predict for an increased likelihood of responding to L. This is the first report associating increased EGFR GCN with sensitivity to L. These results warrant further investigation on a larger sample of patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3095.
Curcumin Modulates Tamoxifen Response in Resistant Breast Cancer Cells.
Authors: De Gasperi M. , Cavazos D. , deGraffenried L. 
Published: December 2010

Abstract
Despite significant improvement in both detection and treatment, breast cancer remains the second leading cause of cancer deaths for women in the United States. Tamoxifen is the most commonly used treatment for estrogen receptor positive (ER+) breast carcinoma, yet up to 50% of patients with metastatic disease present with de novo resistance to tamoxifen, and almost all patients will eventually become resistant to tamoxifen treatment. The mechanism(s) for this resistance appear to be largely dependent upon activation of growth factor signaling pathways. Aberrant activation of the PI3K/Akt and MAPK pathways and their cross talk with both the genomic and nongenomic activity of the ER is implicated in tamoxifen resistance. Breast cancer cell lines with constitutively activated Akt are characterized by high levels of the pro-survival transcription factor Nuclear Factor kappa B (NF-kB), estrogen-independent growth, and resistance to tamoxifen treatment. Studies have shown that curcumin, a polyphenol derived from the rhizome of the perennial herb Curcuma longa, is able to inhibit the activation of NF-kB, which is implicated as one mechanism by which breast cancer cells become resistant to tamoxifen treatment. Previous studies in our laboratory have demonstrated that inhibition of NF-kB is sufficient to sensitize MCF-7 cells that have constitutively activated Akt and elevated NF-kB levels to tamoxifen treatment. However, clinical NF-kB inhibitors such as Velcade generally involve suppression of the proteosome, leading to severe toxicities. Therefore, identification of alternative approaches for suppressing NF-kB activity in the absence of toxicity could prove beneficial for enhancing response to tamoxifen. In the present study, we assessed the efficacy of curcumin at inhibiting breast cancer cell proliferation and survival both as a single agent and in combination with tamoxifen in MCF-7 cells that expressed both “normal” levels of Akt (Control) activity as well as those that expressed the constitutively active form of Akt (myrAkt). As has been previously reported, curcumin treatment inhibited survival and proliferation in the Control MCF-7 cells, but importantly curcumin was also able to suppress survival and proliferation in the myrAKT MCF-7 cells. Curcumin and tamoxifen co-treatment was found to synergistically inhibit survival in myrAKT MCF-7 cells. These findings demonstrate that curcumin can sensitize myrAKT MCF-7 cells to tamoxifen treatment. This preliminary data suggests that the combination of natural NF-kB inhibitors such as curcumin with tamoxifen may be a viable strategy to either prevent tamoxifen resistant disease or to re-sensitize refractory disease to tamoxifen treatment.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3098.
Evaluation of Costs and Impact in Quality of Life in Patients with Surgical Site Complications after Breast Cancer Surgery.
Authors: Arrieta-Joffe P. , Cerezo O. , Bargallo E. , Cruz E. , Lozano A. , Vilar-Compte D. 
Published: December 2010

Abstract
Background: Surgical site complications (infection, dehiscence, necrosis) continue to be an important cause of morbidity in patients undergoing breast cancer surgery. It seems to have a negative impact in quality of life and an increase in health-care costs in comparison with patients with a satisfying outcome.Meterial and Methods:Using two questionnaires to evaluate quality of life from the European Organization for the Research and Treatment of Cancer (EORTC), QLQ-C30 and BR-23, we analyzed 90 breast cancer patients after surgery. We obtained information about direct costs (gloves, gauze, antibiotics, wound dressing, hospital admission) and indirect costs (travel time, transport, day off at work) related to post-surgery consults. We analyzed dissimilarities concerning self-perception of quality of life between patients with and without surgical complications and differences in health-care treatment costs.Results: Twelve (11.76%) patients developed surgical site infection (SSI), 6 (5.88%) necrosis and 9 (8.8%) dehiscence.Self-perception of quality of life was decreased in patients with surgical site complications.The crude median costs of complicated patients was $1,368 US dollars compared to $992 US dollars in non-complicated patients. After adjusting costs according to type of complications only statistical significance was found in patients with SSI and dehiscence (95% confidence interval, $203-$301 and $94-$170 respectively) and the direct costs showed the most important difference.Discussion: The direct and indirect costs was superior in complicated than in non-complicated patients and there was a decrease in self-percieved quality of life, which is consistant with other findings. This should awaken interest in applying new methods to reduce risk of surgical site complications. There is an important lack of evidence regarding quality of life and costs related to post-surgery complications in any health care facilities in our country, which wil make this the first study to do it, specially in breast cancer patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3110.