bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-13-01: Effects of 12-Week Resistance Training on Strength, Fatigue Syndrome and Quality of Life with Breast Cancer Patients during Chemotherapy
Authors: Baumann FT , Leskaroski A , Knicker A , Krakowski-Roosen H , Bloch W , Harbeck N. 
Published: April 2011

Abstract
Introduction: Up to 100% of all breast cancer patients are suffering from fatigue during chemotherapy [Mock 2001, Jacobsson 1998, Irvine 1994]. Causality as well as the treatment of this non-uniform symptom complex is yet unclear. Exercising studies show a positive effect of endurance training on the development of fatigue [Dimeo 2003]. The study situation regarding feasibility and efficiency of pure resistance training with breast cancer patients with fatigue is still unsatisfactory [De Backer 2009, Courneya 2007].
Methods: In this prospective, controlled, randomized study 32 female patients were recruited 6 weeks after operation. 20 probands (IG) accomplished a 12-week resistance training (2 x per week, 60 min each with 75% of the maximum voluntary capacity) during adjuvant chemotherapy. The control group (CG, n=12) did not train. The measurements took place before and after the intervention and maximally isometric and isocinetic strength was tested with the Isomed 2000. Quality of life was evaluated with the EORTC QLQ-C30 inclusive module BR23 and fatigue symptoms by the MFI questionnaires.
Results: No exacerbations could be observed during the study. Strength (p=0.029), fatigue (p=0.048) and different ranges of the quality of life significantly improved in IG, while in CG fatigue and quality of life worsened. 4 out of 5 ranges of the fatigue diagnostic (f.e. General Fatigue, p=0.01) as well as nearly all ranges of the quality of life evaluation were significantly different between IG and KG. In addition, muscle strength (of the arm concerned) showed significant differences between the groups (p=0.032).
Discussion: It could be shown for the first time, that maximum strength testing as well as resistance training with breast cancer patients were feasible already 6 weeks post-OP. Positively, the increase in muscle power, the reduction of fatigue symptoms and the improvement of the quality of life occurred despite concurrent cytotoxic treatment. We rate the high acceptance of the training program as a success. Based on the positive results and the past studies [De Backer 2009, Courneya 2007] we recommend the integration of strength training into the early rehabilitation of breast cancer patients. We note that this study will be completed by December 2010 yet further studies have to be conducted, in order to better understand the effects of different training intensities. Literature:
Courneya et al.: JCO 2007; 25: 4396-4404
Dimeo et al.: Sup Care in Canc 2003; 11:S623-628
Irvine et al. Cancer Nurs 1994; 17: 367-378
Jacobsson et al. J Pain Symptom Manage 1999;18 (4): 233-242
Mock V. Cancer Suppl 2001; 92 (6): 1699-1707
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-13-01.
Abstract P2-13-02: Phase II Study of Glucosamine with Chondroitin on Joint Symptoms Induced by Aromatase Inhibitors in Breast Cancer Patients
Authors: Greenlee H , Crew KD , Shao T , Kranwinkel G , Brafman L , Kalinsky K , Maurer M , Tsai WY , Hershman DL. 
Published: April 2011

Abstract
Background: Aromatase inhibitors (AIs) are commonly used as adjuvant endocrine therapy in postmenopausal women with hormone receptor-positive breast cancer (BC). However, many patients treated with AIs experience joint symptoms which may lead to non-adherence to treatment. We examined whether glucosamine plus chondroitin improves AI-induced arthralgias in women with early stage BC.
Methods: This is a single-arm Phase II study evaluating the efficacy of glucosamine and chondroitin in postmenopausal BC patients with moderate to severe AI-induced arthralgias. Patients took glucosamine sulfate (1500mg/d) + chondroitin sulfate (1200mg/d) for 24 weeks, and were assessed every 6 weeks. The primary endpoint was change in Outcome Measure in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria at 24 weeks. Secondary endpoints include changes in Brief Pain/Stiffness Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis (WOMAC), Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH), quality of life, grip strength and estradiol level. A Simon two-stage design was used. If 7/22 responses were observed, the trial would continue. Results: Of 36/46 patients enrolled to date, 21 were evaluable at 24 weeks. Median age: 61 (46-80); White/Hispanic/Black/Asian: 11/5/4/1. At 24 weeks, 12/21 patients (57%) had improved pain/stiffness or function in their knees or hips, and 14/21 patients (67%) had improvement in their hands, and 80% had improvement in hands and/or knees. There were also decreases in BPI pain/stiffness severity and functional interference (P&lt;0.05). Reassuringly, there was no increase in serum estradiol levels. Conclusion: Glucosamine and chondroitin is a well-tolerated and potentially effective treatment for AI-induced arthralgia. Evaluation of these agents in a placebo controlled phase III study is warranted.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-13-02.
Abstract P2-14-04: Co-Administration of GnRH-Agonists with Adjuvant Chemotherapy in Young Breast Cancer Patients: The Effect on Ovarian Function and on Clinical Outcome
Authors: Goldberg H , Stern M , Risel S , Kuten A , Evron E , Peretz T , Katz D. 
Published: April 2011

Abstract
Background: Loss of fertility is a major concern for young breast cancer (BC) patients who require adjuvant chemotherapy. The risk of ovarian failure depends on patient's age and chemotherapy regimen. Use of GnRH agonists (GnRHa) has been proposed as a mean for ovarian function preservation but has been investigated mainly in small single arm studies. Objectives: To evaluate ovarian function preservation and disease free survival (DFS) in young breast cancer patients following GnRHa and adjuvant chemotherapy co-administration. Methods: In this multicenter retrospective study, we reviewed medical records of 560 breast cancer patients diagnosed before the age of 40, from 1990 through 2006. All patients were treated in one of 5 Israeli cancer centers with standard adjuvant or neoadjuvant chemotherapy regimens with curative intent. GnRHa were prescribed at the discretion of the treating physician. Ovarian function preservation was determined by resumption of menses, premenopausal hormonal profile or pregnancy during follow up. Multivariate analysis was applied in order to determine whether coadministration of GnRHa with chemotherapy affects DFS. Results: Data was available for 71 patients who received GnRHa during chemotherapy (group A), 60 of those were evaluable for fertility and 68 were evaluated for DFS. The group not receiving GnRHa included 460 patients (group B). Of those 207 were evaluable for fertility and 370 for DFS. Data concerning patients’ characteristics and outcome in each group are presented in the table 1. In a Cox regression model including age, stage, ER/PR status and GnRHa administration, the latter variable predicted a better DFS rate (RR 0.31; 95% CI 0.16-0.70; p=0.003), excluding the subgroup with ER/PR positive tumors (p=0.128). This probably reflects selection bias of prognostic factors not included in the analysis and not a real anti neoplastic hormonal effect. Conclusions: Patients who received GnRHa were younger and had less advanced disease. Fertility was preserved independent of GnRHa administration and regardless of cumulative doses of cyclophosphamide or taxans. This observation suggests that GnRHa are unnecessary for fertility preservation in patients younger than 40yrs. No detrimental effect of GnRHa during chemotherapy was observed on disease outcome.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-04.
Abstract P2-16-03: Sorafenib in Combination with Paclitaxel as a First-Line Therapy in Patients with Locally Recurrent or Metastatic Breast Cancer: Overall Survival Results from a Double-Blind, Randomized, Placebo-Controlled, Phase 2b Trial
Authors: Bondarde S , Kaklamani V , Prasad Sahoo T , Lokanatha D , Raina V , Jain M , Schwartzberg L , Gradishar WJ. 
Published: April 2011

Abstract
Background: Sorafenib (SOR) is an oral multikinase inhibitor that targets tumor growth and angiogenesis. We previously reported progression-free survival (PFS) data from the primary analysis of NU07B1 (SABCS 2009 abstr 44), a phase 2b trial assessing the combination of SOR + paclitaxel (PAC) in patients with advanced breast cancer (BC). Here we report overall survival (OS) data, a secondary endpoint.
Methods: NU07B1 is a multinational (India, United States, Brazil) phase 2b study in HER2-negative patients with locally advanced or metastatic BC. Eligibility criteria allowed prior endocrine or radiation therapy and adjuvant use of taxanes and other chemotherapy. Patients with prior chemotherapy for advanced BC were not eligible. Patients were randomized (1:1) to receive PAC (90 mg/m2 IV weekly, 3 wk on/1 wk off) with placebo (PL) or SOR (400 mg po, twice daily). The primary endpoint was PFS. The sample size was estimated at 220 patients based on patient accrual projections and estimated rate of PFS events. OS analysis was planned after 120 events.
Results: A total of 237 patients were enrolled from June 2007 to January 2009. Study arms were balanced for age (mean, 51.9 y), ECOG performance 0 (45%) and 1 (53%), stage IV disease (85%), visceral metastatic disease (75%), and previous non-metastatic chemo (58%). In the primary analysis, PFS trended in favor of SOR+PAC vs PL+PAC with median PFS of 6.9 vs 5.6 mo (HR 0.79, 95% CI 0.56-1.11; 1-sided log rank P=0.09); Grade 3/4 toxicities included hand-foot skin reaction (30% vs 3%), neutropenia (13% vs 7%), and anemia (11% vs 6%); treatment-related deaths occurred in 2 patients (malaria and liver dysfunction), both in the SOR+PAC arm. Overall survival data are expected by 4th quarter of 2010 and will be presented, as well as updated safety data. Conclusions: Further study with SOR+PAC appears warranted but may require adjustments to the dosing algorithm and patient selection criteria to provide a more defi-nitive assessment of benefit-to-risk profile. OS data will help to determine whether this combination should be pursued further.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-03.
Abstract P2-16-09: Wound Healing and Catheter Thrombosis after Implantable Venous Access Device Placement in 266 Metastatic Breast Cancer Patients Treated with Bevacizumab
Authors: Kriegel I , Fourchotte V , Cottu PH , Fromantin I , Salmon RJ , Esteve M. 
Published: April 2011

Abstract
OBJECTIVES: To determine in a population of metastatic breast cancer the incidence of wound dehiscence after placement of an implantable venous access device (VAD) in patients treated with bevacizumab, observe the optimum interval between placement and initiation of treatment and study the risk of catheter thrombosis.
PATIENTS AND METHODS: Between 1/1/2007 and 31/12/2009, this study enrolled all VADs placed by 14 anesthetists: 273 VADs in patients treated by bevacizumab for metastatic breast cancer and 4196 VADs in patients not treated by bevacizumab. The medical charts of the 266 metastatic breast cancer patients treated with bevacizumab between 1/1/2007 and 31/12/2009 were reviewed up until 1/3/2010. A VAD was placed in all patients (goal standard in our institution). 7 patients in whom the VAD was inserted in another institution were excluded from this study. The VAD was removed and replaced in 14 patients with continuation of bevacizumab after replacement of the VAD
RESULTS: 1 patient was lost to follow-up. Thirteen cases of wound dehiscence occurred in 12 patients requiring removal of the VAD (5,1 %). All cases of dehiscence occurred when bevacizumab was administered during the first 7 days after VAD placement. Bevacizumab therapy was initiated less than 7 days after VAD placement in 150 cases, requiring removal of the device in 12 patients (8.6%). The risk of dehiscence was the same from 0 to 7 days. In parallel, the VAD wound dehiscence rate in patients not receiving bevacizumab was 8/4,197 (0.19%) (Fisher's test significant, P&lt;0.001). No risk factors were identified: anesthetists, learning curves, irradiated patients. In particular, 70 ports were placed by juniors with 6 dehiscences, 80 ports by seniors with 7 dehiscences. VAD thrombosis occurred in 4 patients (1,5 %) 3, 5, 7 and 22 months after VAD placement. In all these cases, VAD placement was at the time of initiation of bevacizumab therapy. In parallel, VAD thrombosis occurred in 51/4,197 (1.2%) patients not receiving bevacizumab (Fisher's test not significant; p=0.43).
The other indications for VAD removal were end of treatment: 3 (0,91 %), mechanical problem other than thrombosis: 6 (1,8 %), local infection without wound dehiscence: 1 (0,31%). Bevacizumab was permanently discontinued in 5 patients related to wound dehiscence and in 1 patient due to extensive skin necrosis. Bevacizumab was continued in the other 7 patients.
CONCLUSION: The risk of VAD thrombosis does not require any particular primary prevention. These data suggest the need to observe an interval of at least 7 days between VAD placement and initiation of bevacizumab therapy. Poor healing is a major complication of VAD, interfering with continuation of chemotherapy and the patient's subsequent management, resulting in a real risk of loss of chance.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-09.
Abstract P2-16-11: Metronomic Chemotherapy with Cyclophosphamide (CY) and Doxorubicin (DOX) Inhibits Tumor Growth and Metastases Development of Mouse Mammary Adenocarcinoma M-406
Authors: Mainetti LE , Fernandez Zenobi MV , Rozados VR , Scharovsky OG. 
Published: April 2011

Abstract
Metronomic chemotherapy refers to the chronic, equally spaced, deliver of low doses of different chemotherapeutic drugs, without extended interruptions. We have already demonstrated that the administration, as an intervention strategy, of metronomic CY plus Celecoxib in M-406 and M-234p mammary adenocarcinomas-bearing mice, inhibited tumor growth and metastases development, increasing the survival rate. Our present aim was to study the effect of metronomic chemotherapy with CY + DOX in the M-406 tumor-model. CBi inbred mice were s.c. and i.v. challenged with M-406 cells. On day 9 (s.c.) and day 3 (i.v.), mice were distributed in four experimental groups (n=5-6/group) that received: I) Control: 0.2ml of saline i.p. 3 times/week; II) CY (20mg/kg of body weight, daily) in the drinking water; III) Dox, i.p., 0,5mg/kg, of body weight, 3 times/week; IV) Treatment II + III. Tumors were measured and body weight was determined twice a week. Blood samples were taken at the beginning and at the end of the experiments, to determine total leukocytes count. In the M-406 s.c. model, by day 19, a significant inhibition of tumor growth was evident in group II and IV with respect to control mice (P&lt;0.01). Moreover, on day 41 the tumor volume of animals in group IV was significantly lower than that in group II. Also in group IV, 1 mouse over 6 showed a complete remission. The survival of mice in group IV was significantly higher than in the three other groups. In fact, on day 54, when all the animals belonging to groups I, II and III had already died, 5/6 mice in group IV were alive. In the M-406 i.v. model, animals were sacrificed on day 24 when the first mouse showed metastatic illness signs. The number of lung metastasis was significantly lower in group IV when compared to the control group (P&lt;0.05). The animals in groups II and III (with single-drug treatments) showed intervening values. The total metastatic volume (Σeach metastasis volume) in groups II, III and IV was lower than that of group I (P&lt;0.01), the group IV showing the lowest one. In both experiments (s.c. and i.v.) the treatment was devoid of toxicity, as evaluated by body weight evolution and, importantly, by total leukocytes count. These results clearly show that metronomic chemotherapy with a combination of cyclophosphamide and doxorubicin as an intervention strategy is able to inhibit significantly tumor growth and metastasis development in the M-406 mammary adenocarcinoma tumor-model, while being devoid of toxicity. To our knowledge, this is the first time that a metronomic schedule combining cyclophosphamide and doxorubicin is employed for the treatment of a mammary adenocarcinoma. The characteristics and the effect of the therapeutic schedule herein utilized suggest its implementation at the clinical setting in the near future.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-16-11.
Abstract P2-21-01: The Potential Utility of Curcumin and/or Herceptin in the Treatment of HER-2 Overexpressed Breast Cancer — An In Vitro and In Vivo Comparison Study
Authors: Lai H-W , Kuo S-J , Chen S-T , Chen D-R. 
Published: April 2011

Abstract
Despite the success of herceptin, a significant proportion of HER-2 positive breast cancer patients responded poorly to the treatment. Curcumin (diferuloylmethane), derived from Curcuma longa L., can inhibit the formation of tumors, induce apoptosis, and act on a variety of signal transduction pathways. We have hypothesized that the property of curcumin to downregulate EGFR, HER-2 oncoprotein, and signal transduction pathway of PI3K/Akt, and MAPK may be used in the treatment of HER-2 over expressed breast cancer. In this preliminary study, we showed curcumin decrease the viability of various breast cancer cell lines (MCF-7, MDAMB-231, MCF-10A, BT-474 and SKBr-3(herceptin resistant, hr)). The combination of curcumin did not interfere with the action of herceptin. The herceptin sensitive BT-474 and herceptin resistant SKBr-3(hr) were all sensitive to curcumin treatment. In western blot analysis, the phosphorylation of HER-2, Akt, MAPK were reduced in BT-474 cells when treated with herceptin. In SKBr-3(hr) cells, the addition of herceptin did not downregulate the phosphorylation of HER-2, Akt, and MAPK. When treated with curcumin, the phosphorylation of HER-2, Akt, and MAPK of SKBr-3(hr) were decreased combined with the downregulation of HER-2 oncoprotein in a dose and time dependent manner.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-21-01.
Abstract P3-01-01: Cyfra 21-1 Is Correlated with Circulating Tumor Cells Detection and Patient Outcome in Metastatic Breast Cancer: Results of a Substudy of the Prospective IC 2004-06 Trial
Authors: Bidard F-C , Hajaje D , Bachelot T , Brain E , Campone M , Delaloge S , Mathiot C. 
Published: April 2011

Abstract
Background: The Cyfra 21-1 epitope is a polypeptide originating from cytokeratin-19 fragments possibly released by cell death and was an interesting serum marker in small and/or retrospective studies in breast cancer. On the back of circulating tumor cell (CTC) detection, the prospective IC 2006-04 study planned serum markers (CEA, Ca15.3, Cyfra 21-1) measurements.
Methods: Metastatic breast cancer patients were included in a multicentric non-interventional study before the start of the 1st line chemotherapy. Blood biomarkers, including CTC detection (CellSearch®, ≥5CTC/7.5ml), were analyzed at 4 different times: before the start of the chemotherapy, before cycle 2 (ie mostly at day 21), at first tumor evaluation (ie before cycle 3/4) and at tumor progression.
Results: 191 of the 267 patients included had Cyfra 21-1 assessed at inclusion. CTC level was ≥5CTC/7.5ml in 44% of the cases. Cyfra 21-1&gt;ULNV (in 65% of pts) was not correlated with tumor ER/PR/HER2 status but strongly correlated with PS (p=8e-04), number of metastatic sites (p=0.0001), Ca15.3 (p=0.009), CEA (p=0.005), LDH (p=7e-08) and CTC detection (p=2e-06).
CTC (≥5CTC/7.5ml) and Cyfra21-1 (&gt;ULNV) correlation (N patients)
The effectiveness of curcumin in the treatment of HER-2 overexpressed breast cancer was further confirmed through in vivo BT-474 xenograft model. The comparable ability of curcumin to inhibit cell proliferation, mobility, and angiogenesis as herceptin, combined with the potential ability to overcome the herceptin resistance, curcumin may be a novel agent in the treatment of HER-2 overexressed breast cancer.
Logistic regression showed that LDH (p=0.0005) and CTC (p=0.0004) were the two independent predictors of Cyfra 21-1 elevation. Baseline Cyfra 21-1 &gt;ULNV was associated with early tumor progression (RECIST, p=0.03). In multivariate analysis including standard biomarkers (without CTC), baseline Cyfra 21-1 was independently associated with PFS (p=0.008, RR), together with PS (P&lt;0.001), triple-negativity (P&lt;0.001) and CEA (p=0.02). Multivariate analysis with CTC, subsequent Cyfra 21-1 analyses (cycles 2, 3-4 and progression) and correlation with tumor response and PFS will be will be shown at the meeting. Conclusion: Cyfra 21-1 is a commonly elevated serum marker in metastatic breast cancer and has an independent prognostic value. Although highly correlated, Cyfra 21-1 appears to be more frequently positive in metastatic breast cancer patients than CTC count. Multivariate analyses comparing CTC and Cyfra 21-1 at different time points will be shown at the meeting.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-01-01.
Abstract P3-01-02: Quantitative Analysis and Diagnostic Significance of Methylated SLC19A3 DNA in the Plasma of Breast Cancer Patients
Authors: Ng EKO , Leung C , Shin VY , Chan A , Wong CLPL , Ma ESK , Jin HC , Chu KM , Kwong A. 
Published: April 2011

Abstract
Background: Previously, we have examined the methylation status of SLC19A3 (solute carrier family 19, member 3) promoter and found that SLC19A3 was epigenetically down-regulated in gastric cancer. Here, we aim to develop a new biomarker for cancer diagnosis using methylated SLC19A3 DNA in plasma.
Methods: SLC19A3 gene expression was examined by RT-qPCR. Methylation status of SLC19A3 promoter was evaluated by methylation-specific qPCR. A robust and simple methylation-sensitive restriction enzyme digestion and real-time quantitative PCR assay was developed to quantify SLC19A3 DNA methylation in plasma. Results: Expression of SLC19A3 was significantly down-regulated in 80% (12/15) of breast tumors (P &lt; 0.005). Breast tumors had significant increase in methylation percentage when compared to adjacent non-tumor tissues (P &lt; 0.05). A total of 155 independent plasma samples from participants including 60 breast cancer, 45 gastric cancer patients and 60 healthy subjects were analyzed. Plasma methylated SLC19A3 DNA yielded a ROC curve area of 77%, sensitivity of 82% and specificity of 60% in discriminating breast cancer from control subjects. This marker yielded a ROC curve area of 87%, sensitivity of 90.0% and specificity of 62% in discriminating gastric cancer from control subjects. Elevated level in plasma has been detected not only in advanced stages but also early stages of tumors. Intriguingly, of all DCIS cases from breast cancer patients this plasma marker generated a ROC value of 92%, sensitivity of 100% and specificity of 78% in discriminating DCIS cases from controls. Conclusions: These results suggested that aberrant SLC19A3 promoter hypermethylation in plasma may be a novel biomarker for early breast cancer diagnosis.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-01-02.