bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD04-10: Genome-Wide Copy Number Analysis of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients
Authors: Magbanua MJM , Sosa EV , Scott JH , Pinkel D , Rugo HS , Park JW. 
Published: April 2011

Abstract
Background: Clinical studies have demonstrated the prognostic and predictive value of the number of CTCs in metastatic breast cancer. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment.
Methods: Ten to twenty mLs of blood from 32 metastatic breast cancer patients with poor prognosis (≥5 CTCs in 7.5mLs blood) were subjected to immunomagnetic enrichment. Pools of ∼20 CTCs [EpCAM+, CD45-, nucleated] were isolated via fluorescence activated cell sorting, FACS. Genomic DNA was subjected to whole genome amplification followed by array comparative genomic hybridization (CGH) analysis. Serial genomic profiling was performed in three patients. Genomic profiles from archival primary tumor available from 4 patients were compared to matched CTCs. Copy number analysis was performed using the Nexus® Copy Number. Genomic alterations with p ≥0.05 were considered significant. Results: Genomic profiling of CTCs revealed significant recurrent (≥35%) genomic alterations including gains in 8q12.1, 8q24 and losses in 1p36, 4p16, 5q21, 10q22, 11q24-25, and 13q34. Good concordance of CGH profiles obtained from CTCs isolated from serial blood samples attested to the reproducibility of the assay. Furthermore, comparisons of CTCs with matched archival primary tumors confirmed shared lineage with some divergence.
Conclusions: Copy number analysis revealed common genomic alterations in CTCs as well as shared aberrations with matched primary tumor. In addition, we demonstrated the feasibility of serial genomic profiling of CTCs. Future work will determine associations between genomic aberrations in CTCs and clinicopathological parameters. Uncovering genomic alterations in CTCs may lead to the discovery of therapeutic biomarkers to specifically target these cells in breast cancer patients who respond poorly to current aggressive therapies.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-10.
Abstract PD06-01: A Single Treatment with Targeted Intraoperative Radiotherapy (TARGIT) Is Similar to Several Weeks of External Beam Radiotherapy (EBRT) with Respect to Efficacy and Safety, and Has Obvious Advantages to the Patient and the Economy
Authors: Vaidya JS , Joseph DJ , Tobias JS , Wenz FK , Bulsara M , Alvarado M , Keshtgar MR , Eiermann W , Williams NR , Baum M, 
Published: April 2011

Abstract
Background: After breast-conserving surgery, 90% of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast. Thus, restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients. Materials and methods: Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy (TARGIT) with Intrabeam, we launched the TARGIT-A trial on March 24, 2000. In this prospective, randomised, non-inferiority trial, women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled to compare TARGIT with whole breast external beam radiotherapy (EBRT). The primary outcome was local recurrence in the conserved breast with a predefined absolute non-inferiority margin of 2-5%. Analysis was by intention-to-treat.
Results: 1113 patients were randomly allocated to TARGIT and 1119 were allocated to EBRT. The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1-20% (95% CI 0-53-2-71) in the TARGIT and 0-95% (0.39-2-31) in the EBRT group (difference between groups 0.25%, −1.04 to 1.54; p=0.41). The frequency of any complications and major toxicity (TARGIT 3.3% vs. EBRT 3.9% p=0·44) was similar. Radiotherapy toxicity was lower in the TARGIT group (0.5% vs. 2.1%, p=0.002). 14% of patients who received TARGIT also received EBRT as per the protocol, i.e., the remaining 86% patients could safely avoid 3-6 weeks of daily radiotherapy treatments and its obvious associated costs in economic and human terms.
Discussion: For selected patients with early breast cancer, a single-dose targeted intraoperative radiotherapy should be considered as an alternative to whole breast EBRT delivered over several weeks. It could save time, effort, and money for the patient and the healthcare system, which is particularly relevant in the present times of healthcare reform. NB the main trial results have been presented in ASCO 2010 and published in the Lancet Online First.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-01.
Abstract PD06-08: Size Matters: Incorporation of Sentinel Lymph Node (SLN) Metastasis Size into a Nomogram Predicting NonSLN Involvement in SLN Positive Breast Cancer Patients
Authors: Mittendorf EA , Boughey JC , Degnim AC , Harrell R , Bassett R , Yi M , Meric-Bernstam F , Ross MI , Babiera GV , Kuerer HM , Lucci A , Bedrosian I , Hunt KK , Hwang RF. 
Published: April 2011

Abstract
Purpose: Emerging data from cooperative group trials suggests that not all patients with a positive SLN require completion axillary lymph node dissection (ALND). The controversy regarding who will benefit from additional nodal clearance continues, suggesting a need for improved tools to predict non-SLN involvement. We hypothesized that the size of a SLN metastasis evaluated as a continuous variable would be an important predictor of non-SLN involvement. The goal of this study was to determine clinicopathologic factors including SLN metastasis size that predicted non-SLN involvement and to use these factors to construct an improved predictive nomogram.
Methods: Using a prospective database, we identified 509 patients with invasive breast cancer from 1996 - 2007 with a positive SLN who underwent ALND. Patients receiving neoadjuvant therapy were excluded. Clinicopathologic data including age, primary tumor size, presence of multifocal disease, histology (invasive ductal vs. invasive lobular vs. mixed invasive), tumor grade, estrogen receptor, progesterone receptor, and HER2/neu status, presence of lymphovascular invasion (LVI), the number of SLNs identified, number of positive SLNs, the maximum SLN metastasis size and the presence of extranodal extension were recorded. For SLNs described only as containing isolated tumor cells, size was recorded as 0.1 mm. Univariate and multivariate logistic regression analyses were performed to identify factors predictive of positive non-SLNs. Using these variables, a nomogram was constructed and subsequently validated using an external cohort of 464 patients.
Results: On univariate analysis, the following factors were predictive of positive non-SLNs: number of SLN identified (p&lt;.001), number of positive SLN (p&lt;.001), maximum SLN metastasis size (p&lt;.001), extranodal extension (p&lt;.001), primary tumor size (p=.001), LVI (p=.019) and histology (p=.034). On multivariate analysis, all factors remained significant at the 5% level except LVI. A nomogram was created using these variables. When applied to an external cohort, the nomogram was accurate and discriminating with an area under the receiver operating characteristic curve of .73 (95% CI: .68 - .77). Conclusions: SLN metastasis size is predictive for identifying additional disease in the axilla. These data have been incorporated into a nomogram that accurately predicts the likelihood of having additional, non-SLN metastasis suggesting that routine reporting of the SLN metastasis size would assist with clinical decision making regarding the need to perform a completion ALND. Figures available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD06-08.
Abstract PD07-06: Basal-Like Molecular Subtype Predicts Response to Neoadjuvant Chemotherapy with Epirubicine, Cyclophosphamide, and Docetaxel in Patients with Primary Breast Cancer
Authors: Stickeler E , Klar M , Pils D , Orlowska-Volk M , zur Hausen A , Gitsch G , Tempfer C. 
Published: April 2011

Abstract
Background: Gene expression profiling provides an opportunity to predict response to specific regimens of neo-adjuvant chemotherapy (NAC) in breast cancer patients.
Materials and Methods: In a prospective cohort study of 32 women with primary invasive breast cancer with a measurable lesion, we obtained a tumor specimen by high speed core biopsy before and after 4 cycles of NAC with epirubicine 90mg/m2 and cyclophosphamide 600mg/m2 every 3 weeks, followed by 4 cycles of docetaxel 100mg/m2. Total RNA was extracted from tumor specimens and the whole transcriptome was quantified with Agilent's 44K single color microarray interrogating 44000 unique human genes. Tumor lesions were ultrasonographically measured to assess response using Sinn criteria. Data analysis was performed by GeneSpring v11 and IBM SPSS v18.
Results: Using three single sample predictors, 10 tumors were classified as basal-like and 22 tumors were classified as non basal-like. We found that gene expression-based molecular subtype (basal-like vs. non basal-like) (p=0.003), but not tumor grade (p=0.07), estrogen receptor (p=0.1), progesterone receptor (p=0.6), and HER2 status (p=0.4) predicted response to NAC. Specifically, 7/10 basal-like tumors responded to NAC, whereas 19/22 non basal-like tumors did not respond. Comparing gene expression signatures before and after 4 cycles of NAC, we found that all patients with an initial non basal-like tumor retained this tumor type, whereas 5/7 basal-like tumors, including all responders, lost this molecular subtype. Using regression models based on centroid predicition gene sets, complete prediction of response to NAC based on the initial tumor biopsy as well as on the change of gene expression between two tumor biopsies was achieved with a 21 gene list (p=0.000008) and a 23 gene list (p=0.000007), respectively. Of note, both the expression and upregulation of a single gene, ie HER4, predicted response to NAC in 26/32 (81%; p=0.002) and in 23/25 (92%; P&lt;0.001) patients, respectively.
Conclusions: Basal-like molecular subtype and therapy-induced HER4 gene upregulation predict response to NAC with epirubicine, cyclophosphamide, and docetaxel.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-06.
Abstract PD07-07: Indicators of Homologous Recombination Deficiency in Breast Cancer and Association with Response to Neoadjuvant Chemotherapy
Authors: Lips EH , Mulder L , Hannemann J , Laddach N , Vrancken-Peeters M-JFTD , van de Vijver MJ , Wesseling J , Nederlof PM , Rodenhuis S. 
Published: April 2011

Abstract
Background: Tumors with homologous recombination (HR) deficiency are highly sensitive to DNA double strand break (DSB) inducing agents, such as alkylating agents and poly (ADP-ribose) polymerase (PARP)-inhibitors. BRCA1 or BRCA2- mutated tumors, which are HR deficient, have characteristic DNA gains and losses that can be assessed by an array Comparative Genomic Hybridization (aCGH) classifier, one for BRCA1 mutations and one for BRCA2 mutations. We have studied these aCGH profiles together with several other HR deficiency indicators in sporadic breast cancers and we have correlated their presence to neoadjuvant chemotherapy response.
Material and Methods: A total of 163 HER2-negative pre-treatment biopsies were examined, procured from sporadic breast cancer patients scheduled to receive neoadjuvant therapy with doxorubicin and cyclophosphamide. Triple negative (TN) and estrogen receptor positive (ER+/HER2-) tumors were analyzed separately. aCGH was performed to assess BRCA1-like and BRCA2-like profiles. In addition, BRCA1 promoter methylation, BRCA1 mRNA expression and amplification of the BRCA2-inhibiting gene EMSY were analyzed. Response to neoadjuvant treatment was assessed by measuring pathological complete remission (pCR) and near pCR at the time of surgery.
Results: Inactivation of BRCA1 was frequent in TN tumors: 57% of these tumors showed a BRCA1-like profile at aCGH. BRCA 1 promoter methylation and reduced BRCA1 mRNA expression were observed in 25% and 36% of the TN tumors, respectively. The BRCA1-like aCGH profile was not clearly associated with a better neoadjuvant treatment response (58% vs. 48%, p=0.47). In ER+ tumors, a BRCA2-like aCGH profile and the amplification of the BRCA2 inhibiting gene EMSY were frequently observed (43% and 13% respectively). A BRCA2-like aCGH profile was associated with a significantly higher response rate (35% vs. 14%, p=0.014). EMSY amplification and a BRCA2-like aCGH profile occurred together in only one case, suggesting mutual exclusivity. EMSY was not associated with treatment response, questioning the role of EMSY in HR deficiency.
Conclusion: Alterations associated with BRCA1 inactivation are present in about half of the TN breast cancers, but were not predictive of chemotherapy response. In ER+/HER2- tumors, the BRCA2-like aCGH profile predicts sensitivity to DSB-inducing chemotherapy, and possibly as well to new targeted agents, such as the PARP inhibitors. After validation in independent series the aCGH classifiers may lead to a diagnostic test that could assist in neoadjuvant treatment selection.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-07.
Abstract PD07-09: Hypoxia (VEGF-S) Signature and CRYAB Predict Response to Neoadjuvant Anthracycline/Taxane Containing Chemotherapy within Triple Negative and Unselected Breast Tumors
Authors: Cheang MCU , Parker JS , He X , Zhao W , Fan C , Prat A , Carey L , I-SPY Investigators , Perou CM. 
Published: April 2011

Abstract
Background: Aggressive breast tumors are a clinically challenge to manage. A VEGF-signature (VEGF-s) developed in vivo (Hu et al. BMC Med. 09) and the profile of the anti-apoptotic gene and regulator of tumor angiogenesis, CRYAB (Moyano et al. J Clin Invest 06; Dimberg et al. Blood 08), are both associated with distant metastasis. In this study, we sought to test if these two mechanistically related biomarkers predict pathological complete response(pCR) to anthracyline/taxane-based neoadjuvant chemotherapy.
Methods: Gene expression data of pre-treatment fresh frozen tumors were combined, 149 from the ISPY trial (Agilent 44K) and 225 from MD Anderson Cancer Center(MDACC) (Affymetrix HG U133A). Patients from I-SPY were treated with doxorubicin/cyclophosphamide followed by a taxane. Patients from MDACC were treated with paclitaxel followed by sequential fluorouracil-AC. Tumors were classified into intrinsic subtypes using PAM50(Parker et al. J Clin Oncol 09) and Claudin-low(CL) predictor(Prat et al., Submitted). Odds ratios of biomarkers to pCR were determined using logistic regression. Predictive values of multivariable models were estimated using receiver operating characteristic curve. Results: 319 patients had complete data; the pCR rate was similar between the datasets (ISPY 22%, MDACC 20%). Both the VEGF-s and CRYAB were highly expressed within Basal-like(BL) and CL (P&lt;0.0001); these two biomarkers were positively correlated with each other (r: 0.4, P&lt;0.001). In univariate analysis, both VEGF-s (P&lt;0.001) and CRYAB (P&lt;0.001) were significantly associated with pCR. A multivariable test including tumor size, grade, ER, Her2, intrinsic subtypes, VEGF-s and CRYAB, had an AUC value of 0.86 to predict pCR(Table 1). T stage, Her2, intrinsic subtypes and CRYABwere significant.
82 patients with triple-negative tumors within this combined cohort. In univariate analysis, T stage, grade or classifying tumors into BL vs not did not predict pCR; but VEGF-s (p= 0.04) and CRYAB (p = 0.02) were associated with pCR. Multivariable model, including VEGF-s, CRYAB and the clinical variables, had a predictive value of 0.71 to pCR(Table 1), which identified CRYAB as the most significant factor by likelihood ratio test.
Table 1: Multivariable logistic regression models to predict pCR.
Conclusion: VEGF-s and CRYAB expression are associated with aggressive subtypes and may possibly help to predict response of anthracycline/taxane-based neoadjuvant chemotherapy beyond ER, Her2, and intrinsic subtypes.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD07-09.
Abstract PD08-03: Competing Causes of Mortality vs. Breast Cancer Mortality at 5-Years among 9766 Postmenopausal Women with Hormone Receptor Positive Early Breast Cancer Treated on the TEAM Study of Adjuvant Hormonal Therapy
Authors: Jones SE , Putter H , Hasenburg A , van de Velde CJH , Rea D , Vannetzel J-M , Paridaens R , Markopoulos C , Hozumi Y , Seynaeve C. 
Published: April 2011

Abstract
Background: The TEAM (Tamoxifen Exemestane Adjuvant Multinational) trial is a contemporary multinational study of the effects of 5 years of adjuvant hormonal therapy, either exemestane (E) or tamoxifen switching to E (TàE). Five-year results were presented at SABCS 2009 showing no difference in outcome between E vs TàE (Rea D, SABCS Abstract 11), thus giving us the opportunity to analyze the causes of mortality in the entire population of 9766 women.
Methods: Postmenopausal women with hormone receptor positive (HR+) early breast cancer (BC) were randomized to E or TàE for 5 years after completion of surgery, adjuvant chemotherapy (when indicated), and radiation therapy based on local guidelines. All data were collected and analyzed at the Central Data Center in Leiden. The primary outcome of DFS as well as safety and other secondary outcomes were analyzed in 2009 after 1285 events had occurred to trigger the analysis. Results: Between 2001 and January 2006, 9766 women were randomized; 100% were HR+, 50% had node negative disease, 68% received adjuvant radiotherapy, and 36% received adjuvant chemotherapy. The median follow-up was 5.1 years with over 60% of women having been followed for 5 or more years. Among 961 deaths, 568 (59%) were caused by BC and 393 (41%) by causes other than BC. The cumulative incidence of death from BC vs. other causes at 5-years for all women and by nodal status is as follows (see table):
There was a general relationship with non-breast cancer deaths and increasing age at diagnosis (≥70 years), as expected. Non-breast cancer causes of mortality included second malignancy (105); cardiac (71), cerebral (33), or pulmonary (28) events; miscellaneous other causes (105); and unknown (51).
Conclusions: Among 9766 postmenopausal women with HR+ BC treated with contemporary hormonal strategies following standard primary treatment, the probability of death from causes other than BC was nearly as high as the probability of dying from BC.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-03.
Abstract PD08-09: Impact of a Telephone-Based Exercise Intervention on Physical Activity Behaviors and Fitness in a Cooperative Group Setting
Authors: Ligibel JA , Meyerhardt J , Najita J , Shockro L , Campbell N , Pierce J , Paskett E , Shapiro C. 
Published: April 2011

Abstract
Observational studies have demonstrated a 30-50% lower risk of disease-specific and overall mortality in physically active breast and colorectal cancer patients as compared to sedentary individuals. However, there have been no randomized trials looking at the impact of physical activity on cancer outcomes, and the optimal design of such a trial is not yet well-defined. The Active After Cancer Trial (AACT) is a multicenter feasibility study designed to evaluate the ability of a telephone-based intervention to increase physical activity in patients with breast and colorectal cancer. Methods: Sedentary (reporting less than 60 minutes/week of recreational activity) individuals with stage I-III breast or colorectal cancer were eligible for enrollment after completion of all adjuvant chemotherapy and radiation. Participants were randomized 1:1 to a centralized telephone coaching intervention, with a target goal of 180 minutes/week of physical activity, or to a usual care control group. Intervention participants received an average of 10 telephone contacts over 16-weeks. Initial calls focused upon building self-efficacy and later calls concentrated upon relapse prevention and maintenance of exercise behaviors. Participants underwent assessment of physical activity behaviors (7-Day Physical Activity Recall), fitness (6-Minute Walk Test), physical functioning (EORTC QLQ C-30), fatigue (FACIT) and exercise self-efficacy at baseline and 16 weeks after enrollment.
Results: One hundred and twenty-one patients were enrolled through 10 Cancer and Leukemia Group B (CALGB) institutions; 100 patients had breast cancer and 21 had colorectal cancer. Average age was 54.3, 74% of patients had received chemotherapy and mean time since completion of adjuvant treatment was 24 months. Participants randomized to the exercise group experienced significant improvements in fitness and physical functioning as compared to controls.
Table. Baseline measures and change (post-minus pre) scores in intervention and control patients (±SD)
Intervention participants also reported a doubling in minutes of weekly physical activity, but this was not a significant increase compared to controls.
Conclusions: Sedentary breast and colorectal cancer survivors can be enrolled in a physical activity intervention. A centralized telephone coaching intervention successfully increased fitness and physical functioning, although self-reported exercise time was not significantly changed. A large-scale clinical trial within the co-operative groups is feasible.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-09.
Abstract PD09-02: Prognostic Effect of Obesity on Breast Cancer
Authors: Tryfonopoulos D , Christakou H , Rapti V , Kontou N , Panopoulos C , Koumakis G , Demiri S , Papadimitriou C , Missitzis I , Apostolikas N , Efremidis A. 
Published: April 2011

Abstract
Background: Body mass index (BMI), prior estrogen use, and family history have been described as risk factors for invasive breast cancer. Our purpose was to investigate the influence of obesity on established prognostic pathologic and molecular characteristics of breast cancer. Material and methods: Five-hundred and twelve female consecutive breast cancer patients of mean age 53±11 years were included in this study. Data were recorded in a prospective electronic databank upon first presentation. Risk factors (BMI, family history, prior estrogen use, menopausal status, parity, metabolic syndrome, smoking, alcohol, hypertension, hyperlipidaemia and diabetes) as well as histologic characteristics (TNM, nodal status, grade, LVI) and tumor phenotype (ER, PR, Cerb-B2) were obtained. Patients with a BMI&lt;27 were considered of normal weight whereas patients with a BMI≥27 were considered as obese. Univariate and logistic regression analysis were performed. Results: The 2 groups did not differ for age (p=ns). Patients with a BMI≥27 were more frequently node positive, had a higher incidence of grade 3, LVI positive tumors and had more often a positive family history of breast cancer (P&lt;0.05). On the contrary, patients with a BMI&lt;27 reported more frequently prior estrogen use and were more commonly nulliparous (P&lt;0.05). Regression analysis confirmed that in patients with BMI&lt;27 age and menopausal status were associated with node positive disease, independently of tumor phenotype, grade, LVI, family history, estrogen use and parity (0.951, 95%CI 0.91-0.99 and 3.232, 95%CI 1.2-8.5). Using the same analysis, in patients with BMI≥27 LVI was associated with node positive disease, independently of all other factors (5.253, 95%CI 1.1-26.9).
Discussion: Different risk factors appear to influence lean and obese breast cancer patients. Patients with BMI&lt;27 more frequently have a history of estrogen use and nulliparity. Age and menopausal status are independently associated with node + disease in lean patients. Obese patients (BMI&gt;27) have more frequently positive family history and more aggressive histology (node +, grade 3, LVI+). LVI in obese patients appears to be independently associated with node + disease.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD09-02.