bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic Utility of HOXB13:IL17BR and Molecular Grade Index for Node-Negative Breast Cancer Patients.
Authors: Habel L. , Erlander M. , Achacoso N. , Ma X. , Sgroi D. , Fehrenbacher L. , Greenberg D. , Quesenberry C. 
Published: December 2010

Abstract
Background: Four studies have reported that a two-gene ratio (HOXB13:IL17BR) may be prognostic and/or predictive of tamoxifen benefit among early stage breast cancer patients. More recently, a 5-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) was reported to predict clinical outcome. We evaluated the performance of these two gene signatures among an independent population of lymph node-negative breast cancer patients from a community hospital setting.Methods: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985-94 and not treated with adjuvant chemotherapy (Habel, 2006). Archived tumor tissues were available on 169 cases (breast cancer deaths) and 335 matched controls and, using RT-PCR, were analyzed for expression levels of the above 7 cancer-related genes and 4 reference genes. Logistic regression methods were used to estimate the 10-year risk and the relative risk (RR) of breast cancer death associated with pre-specified risk categories based on cross-classification of HOXB13:IL17BR and MGI scores.Results: Approximately 50% of patients were classified as low risk by the HOXB13:IL17BR+MGI risk classifier. At 10 years, the risks of breast cancer death for ER+, tamoxifen-treated patients were 3.9% (95% confidence interval (CI) 2.2% - 5.5%), 5.6% (95% CI 2.6% - 8.5%), and 15.6% (95% CI 8.7% - 21.9%) for those in the low, intermediate and high risk groups, respectively. They were 5.9% (95% CI 4.2% - 7.5%), 15.2% (95% CI 8.3% - 21.5%), and 16.5% (95% CI 10.4% - 22.2%) for ER+ patients not treated with tamoxifen. After adjusting for tumor size and grade, the RRs of breast cancer death associated with high vs. low HOXB13:IL17BR+MGI risk categories were attenuated but remained elevated in both treatment groups; the RR continued to be statistically significant in tamoxifen treated patients only.Conclusion: In this population of lymph-node negative patients not treated with adjuvant chemotherapy, the HOXB13:IL17BR+MGI risk classifier was predictive of risk of breast cancer death and appeared to provide risk information beyond standard prognostic factors.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4034.
Polysomy of Chromosome 17 in Breast Cancer.
Authors: Nielsen K. , Ejlertsen B. , Møller S. , Balslev E. , Müller S. , Knoop A. , Mouridsen H. 
Published: December 2010

Abstract
Purpose: Polysomy of chromosome 17 is frequently described in breast cancer, but firm definition of polysomy is lacking. We have used normal breast tissue to define the ploidy levels in the truncated nuclei of cut sections based on standard cytogenetic definition of ploidy in whole nuclei. Data from patients with invasive breast cancer enrolled in a randomized clinical trial was used to investigate the effect of polysomy of centromere 17 on patient survival. (Ejlertsen B et al., Eur J Cancer 2007:43:877-84).Material and methods: Fluorescence in situ hybridization (FISH) with TOP2A/CEN-17 was performed on 120 normal breast specimens. Centromere 17 (CEN-17) measurements from matching HER2/CEN-17 and TOP2A/CEN-17 FISH data was available from 649 patients from a previously published biomarker study (Knoop A et. al., J Clin Oncol 2005;23:7483-90).Results: Two thirds of the tumors had an average number of CEN-17 signals below two and 10% had more than three average CEN-17 signals. Monosomy (&lt;1.25 CEN-17/nucleus) of centromere 17 was observed in 8% of the tumors, 60% of the samples were diploid (1.26-2.09 CEN-17/nucleus), 22% triploid (2.10-2.93 CEN-17/nucleus), 5% tetraploid (2.94-3.77 CEN-17/nucleus) and 5% of the tumors had higher ploidy level (&gt;3.78 CEN-17/nucleus). In the aneuploid tumors and especially in the highly polyploidy tumors, amplification is the most frequent event in the HER2 assay whereas deletions increased with the ploidy level in TOP2A assay. Increasing ploidy was associated with decreased overall survival (P=0.0001), but multivariate analysis showed that polyploidy was not an independent prognostic factor neither predictive for treatment outcome.Conclusion: Polysomy 17 is a rare event in tumor samples from patients, but correlate to HER2 amplification and TOP2A deletion. However, inclusion of a reference probe is necessary if deletions are to be revealed and to avoid false positive amplified cases with a high proportion of dividing cells or a doubling of the DNA content. Very high polyploidy is associated with poor survival but is not an independent prognostic factor when other prognostic factor are included in a multivariate analysis. In this large clinical study, polysomy 17 was neither an independent prognostic nor predictive marker.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4035.
Prognostic Factors and Long-Term Survivors in Inflammatory Breast Cancer.
Authors: Woods R. , Huang J. , Livingston R. , Grasso-LeBeau L. , Hendershott K. , Gruessner A. , Mayo J. , Lang J. 
Published: December 2010

Abstract
Background: Inflammatory Breast Cancer (IBC) carries a worse overall survival and demonstrates distinct clinicopathologic qualities which require refinement of prognostic indicators specific to IBC. We hypothesized that given IBC's typically rapid course, nodal status would not be a significant prognostic factor. We also investigated the impact of treatment with radiation and surgery on IBC survival.Material and Methods: Retrospective data from the Surveillance, Epidemiology, and End Results of the National Cancer Institute (SEER 13 and 17 registries) were used to evaluate the prognostic effects of nodal status, surgical resection, and radiation on mortality of patients with IBC. We compared survival between patients with or without positive lymph node status and treatment with radiation, surgery, and those patients treated with both. Data were subjected to multivariate statistical analysis.Results: A total of 3755 IBC patients were diagnosed and reported to SEER between 1995 and 2005. IBC survival appears independent of lymph node status with mean survival times of 34 months for node negative patients and 32 months for node positive patients (figure 1, p= 0.11). We identified 735 cases with adequate local treatment records and follow-up information. In this subset we compared survival between groups that received both surgery and radiation (SR), groups that received one of these therapies independently (S or R respectively), to those without either therapy (NT, no therapy) given positive lymph node status at diagnosis (fig. 2, p&lt;0.001).Discussion: Our data suggests that the prognosis of IBC is not related to lymph node status at the time of diagnosis. Because patients with IBC amenable to surgical intervention or radiation are likely to have more favorable biology then those who progress on chemotherapy, it remains difficult to quantify the impact of local therapies. NCCN guidelines currently recommend first-line chemotherapy before moving to local treatments; therefore one limitation of our study is the assumption that centers reporting data to SEER follow NCCN guidelines. Of special interest is the substantial number of patients that show prolonged survival with local therapies. This supports previous reports that about 30% of patients who complete chemotherapy, surgery and radiation therapy may survive five years or more after IBC diagnosis.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4039.
PI3 Kinase Pathway Analysis in Tissue Microarrays Using Laser Capture Microdissection and Immunohistochemistry.
Authors: Gardner H. , Nuciforo P. , Liu W. , Lee B. , Rheinhardt J. , Barrett C. , Linnartz R. , Dugan M. , Eiermann W. , Pienkowski T. , Martin M. , Robert N. , Forbes J. , Buyse M. , Finn R. , Lindsay M. , Slamon D. , Press M. 
Published: December 2010

Abstract
Background. During the performance of the BCIRG trials primary patient tumor samples were obtained from paraffin blocks and assembled into 15 tissue microarrays, including 3000 samples from trial 005 (adjuvant taxol in Her2- node positive patients), 2200 in 006 (adjuvant herceptin in Her2+ high risk patients) and 300 in 007 (addition of platinum in Her2+ first line therapy). This array set was prepared prospectively, in anticipation of molecular epidemiologic studies of a variety of targets in relation to outcome. In order to address the potentially important role of the PIK3CA pathway in modulating outcome in different clinical situations we assessed components of the PIK3CA pathway by various methods.Methods. We analysed the expression of PTEN, Cyclin D1, p53 and Stathmin by immunohistochemistry using standard methods. All markers were scored by histoscore. Phospho S6 240 and phospho Akt 473 were assessed simultaneously by quantum dot immunofluorescence using automated image capture and segmentation. PIK3CA mutations were evaluated using SnaPshot analysis of laser captured TMA spots in a subset of approximately 2000 samples.Results. In the samples analyzed PIK3CA mutation had an incidence of 23%, with 9% being mutations in exon 9 and 13% in exon 20, with 0.5% being mutant in both exons. Initial analysis of the results prior to outcome analysis indicated that Stathmin expression, while being a robust marker with good dynamic range, did not appear to correlate with PTEN loss by IHC or with PIK3CA mutation.Conclusions. PIK3CA mutational analysis is feasible from TMA cores and gives mutation incidences similar to the published literature for archival material. Relationships of markers with outcome will be presented.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4043.
The 70-Gene Profile (MammaPrintTM) Is an Independent Predictor of Breast Cancer Specific Survival for Women 65 Years of Age or Older.
Authors: Bedard P. , Bedard P. , Mook S. , Mook S. , Knauer M. , Knauer M. , Durbecq V. , Bernard-Marty C. , Glas A. , Cardoso F. , Cardoso F. , van 't Veer L. , van 't Veer L. 
Published: December 2010

Abstract
Background: One-half of all new breast cancer diagnoses occur in women age 65 years or older. In this age group, the use of adjuvant chemotherapy is largely influenced by co-morbidity and little is known about the applicability of prognostic multi-gene assays. The 70-gene profile (MammaPrint) is an independent prognostic indicator in early breast cancer, however, its performance in women with breast cancer 65 years or older has not been systematically studied.Methods: Women 65 years or older who were diagnosed at the Jules Bordet Institute and the Netherlands Cancer Institute between 1987 and 2003 with primary breast cancer with 0-3 involved lymph nodes who received either no adjuvant systemic therapy or adjuvant hormonal therapy alone were selected. MammaPrint test results were compared with clinical-pathological risk assessment using Adjuvant!Online.Results: Of 204 women aged 65 years or older (median age 70 years), 129 (63.2%) were classified as genomic low risk and 75 (36.8%) as genomic high risk. After a median follow-up of 8.6 years (range 0.3-17.9), the 5- and 10-year breast cancer specific survival (BCSS) for the genomic low risk group was 96% (SE 2%) and 86% (SE 4%) versus 82% (SE 4%) and 66% (SE 6%) for the genomic high risk group (log-rank p=0.001). In univariate analysis, MammaPrint was prognostic for 5-year BCSS (HR=5.0, 95%CI 1.8-14.1, p=0.002) and 10-year BCSS (HR=3.1, 95%CI 1.6-6.0, p=0.001). In a multivariate model adjusted for 10-year risk predicted by Adjuvant!Online, MammaPrint was independently prognostic for 5-year BCSS (HR=4.4, 95%CI 1.6-12.7, p=0.005) and 10-year BCSS (HR=2.5, 95%CI 1.3-5.0, p=0.009). As in prior validation series, the performance of MammaPrint was time dependent, with improved prognostication for early BCSS (≤5 years).Conclusion: Although a smaller proportion of breast cancers diagnosed in women 65 years or older are classified as high-risk by MammaPrint, it is an independent prognostic indicator that may be useful to select patients that can safely forego adjuvant chemotherapy. Additional data from patients over 70 years of age will be available at the time of the meeting. If these data are confirmatory, the ongoing prospective MINDACT trial will be amended to include older women.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4049.
Serum S100B as a Prognostic Indicator in Patients with Breast Cancer.
Authors: McCartan D. , McIlroy M. , Hill A. , Young L. 
Published: December 2010

Abstract
BackgroundThe nuclear receptor co-activator SRC-1 has recently been implicated as an important mediator of breast cancer metastasis in vitro. These findings are in keeping with previous reports from our group reporting significantly reduced disease free survival in patients who express SRC-1 when compared to those who do not. We identified the developmental protein HOXc11 as interacting with SRC-1 in tamoxifen resistant breast cancer cells. Dysregulation of homeobox genes has been reported in a wide variety of both solid organ and haematological malignancies. The putative target gene of HOXc11, S100B is a secreted protein, known to be of prognostic significance in malignant melanoma. The aim of this work was to examine the relationship between HOXc11, SRC-1 and S100B and their relevance to disease progression in breast cancer.Materials and MethodsAll chromatin immunoprecipitation (ChIP) and proliferation assays were performed in tamoxifen resistant breast cancer cells derived from MCF7s. Immunohistochemistry was performed for S100B, HOXc11 and SRC-1 on a tissue microarray of 560 patients with invasive breast cancer with a median follow up of 6.5 years. S100B was assessed using an ELISA based technique (Diasorin, USA) on serum samples of a prospective cohort of patients with breast cancer prior to any treatment.ResultsChIP assays confirmed recruitment of both HOXc11 and SRC-1 to the promoter region of S100B after treatment with tamoxifen at both 45 minutes and 2 hours when compared to control. Treatment of tamoxifen resistant cells with HOXc11 siRNA resensitised the cells to the anti-proliferative effects of tamoxifen. Immunohistochemistry revealed S100B to be a strong predictor of reduced disease free survival in patients receiving adjuvant endocrine treatment (Hazard ratio 5.82; p&lt;0.0001). Tumour expression of S100B was associated with expression of both HOXc11 and SRC-1 providing translational evidence for a relationship between these proteins. Elevated serum levels (&gt;0.15ug/l) of S100B were found in 10.5% of patients with breast cancer prior to treatment. Elevated S100B correlated with HER2 positivity (Fisher's exact: p=0.005) but not with any of the other standard clinico-pathological factors examined. From a cohort of 80 patients with known medium to long term follow up, elevated serum S100B showed a strong positive correlation with disease recurrence (p=0.017, odds ratio 9.38).DiscussionOur investigations into the prognostic significance of S100B in breast cancer have shown considerable promise. Given it's accessibility as a serum protein, quantifiable by ELISA, it offers potential as a marker for disease recurrence in patients with breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4052.
A Prospective Comparison of Switches in Biomarker Status between Primary and Recurrent Breast Cancer: The Breast Recurrence in Tissues Study (BRITS).
Authors: Jordan LB. , Purdie CA. , Quinlan PR. , Anderson E. , Thompson AM. 
Published: December 2010

Abstract
IntroductionDisease recurrence and metastasis results in morbidity and mortality from breast cancer. In deciding the best therapeutic approaches at the time of recurrence, the molecular phenotype of the original (primary) cancer is often used. However, it is unclear whether the phenotype of the recurrent cancer is unchanged or has evolved from the original primary. Following several retrospective studies, the Breast Recurrence In Tissues Study (BRITS) is the first prospective study to address this clinically important question.MethodsTo detect a clinically significant switch in biomarker status 137 matched primary and recurrent breast cancer tissue samples were prospectively collected (to an estimated 95% confidence with a precision of 5% to detect a switch) from consenting patients and successfully constructed into tissue microarrays (TMA). Central laboratory analysis of ER (clone 6F11, 1:200) PR (clone 16, 1:800) and HER2 (CB11, 1:1200) was performed by two specialist breast pathologists. ER and PR were scored using the Allred method and HER2 status confirmed by FISH for HER2 2+ (primary or metastasis).Results137 women, mean age 62.6 years (range 27-87 years), 83/137 (60.6%) of whom were postmenopausal were successfully examined. For the original primaries, 96/137 (70.1%) were invasive ductal cancer, 17 (12.4%) grade 1, 66 (48.2%) grade 2 and 43 (31.4%) grade 3, mean size of original primary 23.96mm (range 2.0-134.0mm) and 27 (19.7%) multicentric. Lymphovascular invasion was identified in 76/137 (55.5%) and a margin not clear in 18 (13.1%).Time from the original primary to the recurrence biopsy was a median 92.2 months (range 5-327 months), and occurred as locoregional recurrence in 101 (73.7%). The recurrent biopsy was excisional tissue in 100 (73%) and core biopsy in 37 (27%).Central laboratory analysis of the original primary was ER positive in 109 (79.6%), PR positive in 85 (62.0%) and HER2 positive in 14 (10.2%); the recurrent disease was ER positive in 101 (73.7%), PR positive in 75 (54.7%) and HER2 positive in 16 (11.7%). A switch in receptor status, in either direction, was identified for ER in 14 patients (10.2%; p=0.983 Wilcoxon sign rank test), PR in 34 (24.8%; p=0.003 Wilcoxon sign rank test) and HER2 in 4 (2.9%; p=0.074 Wilcoxon sign rank test). In the judgement of the investigators the switch led to a change in the subsequent treatment in 24 patients (17.5%).ConclusionThis prospective study has demonstrated that the management of locally recurrent or metastatic breast cancer should include tissue sampling, since switches of ER, PR or HER2 status in the breast cancer recurrence may change the planned treatment for one in six patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4053.
The Clinicopathologic Characteristics and Clinical Outcomes of Estrogen Receptor-Negative and Progesterone Receptor-Positive Breast Cancer.
Authors: Kang S. , Jeon Y. , Kim C. , Cho Y. , Lee S. 
Published: December 2010

Abstract
Backgrounds: Invasive breast cancer patients with estrogen receptor positive (ER+) or progesterone receptor positive (PR+) tumors are treated by similar treatment strategies. Yet the prognosis of ER-PR+ tumor is currently controversial. The aims of this study were to evaluate the clinicopathologic characteristics and the prognosis of patients with ER-PR+ breast cancer.Materials and Methods: 1570 patients who underwent an operation for stage I-III breast cancer from January 1995 to December 2005 were included in this study. The patients were stratified according to the ER/PR phenotype and our study focused on the ER-PR+ phenotype. The clinicopathologic characteristics and the prognosis of patients with the ER-PR+ phenotype were compared with those of the patients with ER+ (ER+PR- or ER+PR+) breast cancer.Results: The mean age at diagnosis was 47.1 years (age range: 20-88) and the mean follow-up was 65.2 months. The hormone receptor phenotype was “ER-PR+” in 75 cases (4.8%) and “ER+ (ER+PR+ or ER+PR-) in 917 cases (58.4%). A patient age &lt; 35 (p=0.002), a high histologic grade (p=0.004) and C-cerbB2 over-expression (p=0.006) were more frequent for the patients with the ER-PR+ tumors. There was a significant difference between the two groups for the mean age (p&lt;0.001), but there was no difference in the nodal status, the tumor size and the presence of vascular invasion. The 5 year and 10 year disease-free survival (DFS) rates of the ER-PR+ group were 67.2% and 55.3%, respectively, and those of the ER+ group were 84.9% and 73.1%, respectively (p &lt;0.001). The 5 year and 10 year overall survival (OS) of the ER-PR+ group were 82.4% and 62.6%, respectively, and those of the ER+ group were 93.4% and 83.3%, respectively. There was significant difference between the two groups for the OS (p =0.001).Conclusion: ER-PR+ tumors have more aggressive clinicopathologic features than ER+ tumors for the patient age, the tumor grade and the presence of C-erbB2 overexpression. Furthermore, ER-PR+ tumors showed a worse prognosis than did the ER+ tumors. Consequently, the treatment modality and the prognosis of the patients with ER-PR+ tumors probably need to be altered from those of the patients with ER+ tumors.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4054.
Young Age as a Prognostic Factor for Operable Breast Cancer: Significance of Molecular Subtype in Recurrence-Free Survival.
Authors: Kim E. , Han W. , Noh D. 
Published: December 2010

Abstract
Background: Breast cancer is uncommon in young women. Biology of the disease in this age group is poorly understood and the prognostic significance of young age at diagnosis remains controversial. We investigated the clinicopathological characteristics and outcomes of younger breast cancer patients (≤35 years of age), and assessed the prognostic significance of young age according to molecular subtype.Methods: We analyzed 2,474 primary invasive breast cancer patients who underwent surgery between 2000 and 2005. The younger age group consisted of patients aged ≤35 years. Subtypes were defined by expression of hormone receptor (HR) and HER2: luminal (HR+ irrespective of HER2 status), triple-negative (HR- and HER2-) and HER2 (HR- and HER2+).Results: A total of 229 (9.3%) patients were aged ≤35 years. Breast cancers in this age group were associated with larger size, higher lymph node positivity, higher nuclear and histological grades, and elevated Ki-67 index, compared with tumors in older patients. Younger patients had a greater probability of recurrence than older patients (P&lt;0.001). By multivariate analysis, young age remained a significant predictor of recurrence (hazard ratio, 1.54; 95% confidence interval, 1.15-2.06; P=0.004). When the cancer subtypes were considered, young age was a significant predictor of recurrence in patients with both luminal and HER2 subtypes. In patients with the triple-negative subtype, however, young age was not a predictor of recurrence.Conclusions: Young age (≤35 years) was an independent predictor of recurrence for operable breast cancer patients with the luminal and HER2 subtypes, but not for those with the triple-negative subtype.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4063.