bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life in relation to hormonal treatment of postmenopausal women in the Dutch Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial.
Authors: van Nes JG , Voskuil DW , van Leeuwen FE , Junggeburt JM , de Haes HC , van de Velde CJ 
Published: December 2010

Abstract
Abstract #21
Background In the last decade, use of adjuvant hormonal treatment increased as well as its duration. Aromatase inhibitors are associated with a minimal increase of disease free survival compared to tamoxifen. Both therapies are associated with different side effects which can affect quality of life (QoL). Therefore, it is necessary to compare the QoL of patients using these therapies. We compared the QoL of women participating in the Dutch Tamoxifen Exemestane Adjuvant Multicentre (TEAM) Trial.&#x2028; Patients and Methods The Dutch TEAM trial included 2754 postmenopausal early breast cancer patients who were randomised between five years of exemestane or 2.5-3 years of tamoxifen followed by 2.5-2 years of exemestane. A total of 742 patients were invited onto the QoL subprotocol. At one (T1) and two (T2) years after start of hormonal treatment, patients were ask to fill in questionnaires. This questionnaire contains the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and the EORTC BR23 questionnaires, supplemented with Functional Assessment of Cancer Therapy - Endocrine Subscale (FACT-ES) questions covering endocrine symptoms. The endpoint was the difference in QoL between patients receiving tamoxifen or exemestane.&#x2028; Results Questionnaires were completed by 543 patients at T1 and 83% of these returned the questionnaire of T2. There were no significant differences in physical functioning, role functioning, cognitive functioning, emotional functioning, body image, breast symptoms, arm symptoms and endocrine symptoms between both treatment groups at T1 nor at T2. Patients receiving exemestane had significantly less sexual enjoyment (difference of 9 points on a 0-100 scale; p=0.004) and more insomnia (difference of 8 points; p=0.005) compared to patients receiving tamoxifen at T1. At T2, there was no statistically significant difference in sexual enjoyment (difference of 4 points; p=0.287). However, patients receiving exemestane reported significantly worse sexual functioning (difference of 5 points; p=0.020) and still more insomnia (difference of 8 points; p=0.004).&#x2028; Conclusion Patients using exemestane reported less sexual enjoyment and more sexual functional problems than patients using tamoxifen. This may be explained by the fact that specific side effects of exemestane (e.g. vaginal dryness) can cause less sexual enjoyment which can result in a decreased sexual functioning.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 21.
Development and evaluation of a cancer risk educational tool (CREdIT) for women with a family history of breast and ovarian cancer.
Authors: Wilcox C , Lee R , Beattie M , Luce J , Joseph G , Lamvik K , Crawford B , Ziegler J , Braithwaite D 
Published: December 2010

Abstract
Abstract #2101
Introduction: In underserved, lower literacy and multiethnic women at risk of Hereditary Breast and Ovarian Cancer (HBOC), there is a need for culturally appropriate educational tools. The purpose of this Phase I study is to evaluate the use of a Cancer Risk Educational Intervention Tool (CREdIT) as an adjunct to genetic counseling for HBOC for underserved women at San Francisco General Hospital (SFGH).&#x2028; Methods: CREdIT is a 15 minute audio-visual powerpoint story presentation (available in English and Spanish) which employs non-scientific images and language specifically designed for use by our target population. Participant questionnaires, administered before and after the intervention, evaluate patient satisfaction, risk perception, knowledge of cancer genetics, and anxiety. Genetic counselor questionnaires address counselor satisfaction and time-flow.&#x2028; Results: To date, we have recruited 23 women of diverse backgrounds (mean age of 46, range: 26 to 63). Of these, seven (30%) are first-generation immigrants and four (17%) have less than a high school diploma. Eight (35%) have had cancer, and eighteen (78%) reported that cancer runs in their families. We have found an increase in knowledge following the CREdIT presentation, specifically vis-à-vis BRCA inheritance, BRCA-associated cancer risk, and risk-reducing options (all p &lt; 0.05). These improvements occur without an increase in patient anxiety (p &gt; 0.05). All participants believed that the presentation helped them learn more about cancer risk, and genetic counselors reported increased patient preparedness and counselor satisfaction as a result of CREdIT use (p &lt; 0.05). Mean genetic counselor consultation time decreased by 5.5 minutes after CREdIT use.&#x2028; Conclusions: CREdIT appears to increase knowledge and improve understanding of BRCA-associated risks without raising anxiety in underserved women at risk of HBOC. Genetic counselors report increased satisfaction and patient preparedness, and decreased counseling time with CREdIT. Future work will involve examining long-term outcomes of CREdIT use; subgroup analyses to identify patient populations most likely to benefit from CREdIT; further evaluation using clinical trial methodology; and strategies for its dissemination to other settings working with underserved, multiethnic populations.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2101.
A 24-month subgroup analysis of the effect of denosumab on bone mineral density in women with breast cancer undergoing aromatase inhibitor therapy.
Authors: Ellis GK , Bone HG , Chlebowski R , Paul D , Spadafora S , Fan M , Kim D 
Published: December 2010

Abstract
Abstract #2106
Background: Accelerated bone loss and fracture risk are expected consequences of adjuvant aromatase inhibitor (AI) therapy. We previously showed that denosumab, a fully human monoclonal antibody that inhibits RANK ligand (RANKL), significantly increased bone mineral density (BMD) at the lumbar spine and at all measured skeletal sites at 12 months compared with placebo in women with breast cancer undergoing adjuvant AI therapy (Ellis et al, 2007 SABCS). In this analysis, we assessed covariates that may influence treatment effects on BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius at 24 months.&#x2028; Methods: Adult patients (pts) with hormone receptor-positive breast cancer, who had evidence of low bone mass and were receiving adjuvant AI therapy, were enrolled in this randomized, double-blind, placebo-controlled, phase 3 study. Pts were stratified according to length of previous AI therapy (≤ 6 vs &gt; 6 months) and randomly assigned to receive, together with calcium and vitamin D, placebo (n=125) or denosumab 60 mg (n=127) subcutaneously every 6 months for 4 doses. Subgroup analysis was conducted using analysis of covariance and adjusted for treatment, stratification factor, baseline BMD value, densitometer type, and baseline BMD value-by-densitometer-type interaction.&#x2028; Results: At 24 months, greater increases in BMD were seen at all measured skeletal sites (both trabecular and cortical bone) for denosumab compared with placebo, regardless of the subgroup (table). Adverse events (AEs) occurred at a similar rate in both groups (91% denosumab, 90% placebo).&#x2028; Conclusion: In pts with breast cancer undergoing adjuvant AI therapy, twice-yearly denosumab treatment showed consistent increases in BMD across the skeleton at 24 months compared with placebo, regardless of subgroups.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2106.
A pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel plus sorafenib in women with node positive or high-risk breast cancer.
Authors: Spigel DR , Molthrop D , Peacock N , Kommor M , Markus T , Vazquez E , Greco FA , Burris HA , Hainsworth JD , Yardley DA 
Published: December 2010

Abstract
Abstract #2110
Background: Targeting angiogenesis is an effective treatment strategy in many solid tumors including breast cancer (BC). Sorafenib is a small molecule inhibitor of angiogenesis and other tumor growth signaling. We conducted a pilot phase 2 trial incorporating sorafenib into standard adjuvant BC treatment. Material and Methods: The primary endpoint of this multicenter community-based study was to assess the safety of doxorubicin and cyclophosphamide followed by paclitaxel in combination with sorafenib in patients (pts) with node positive or otherwise high-risk BC. Eligibility criteria included: either mastectomy or breast conserving surgery-with axillary node assessment for stage I, II, IIIA, and IIIC (T1-3, N3a only) BC. Pts were either lymph node positive or high-risk node negative (tumor size &gt;2 cm; hormone receptor negative; grade 2-3; or age &lt;35 years). Additional inclusion criteria included: HER2-negative, ECOG performance status 0-1, normal left ventricular ejection fraction by echocardiography or MUGA scan, adequate organ function, and signed informed consent. Treatment consisted of doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) both IV day 1 every 3 weeks x 4 cycles, followed by paclitaxel 175mg/m2 day 1 every 3 weeks x 4 cycles or 80mg/m2 IV weekly x 12, combined with sorafenib 400mg orally twice daily. Sorafenib was held during radiation therapy (where indicated) and resumed once completed. Sorafenib was continued for a total of 12 months and in combination with adjuvant hormonal therapy (where indicated.) LV assessments occurred after AC, paclitaxel, and every 3 months during maintenance sorafenib. Results: Forty-five pts were enrolled from 5/07 to 1/08. The median follow-up is 6 months (range 4-12 months). Baseline characteristics included: median age 54 years (35-74); ECOG 0, 93%; node positive, 80%; and hormone receptor negative 33%. Nineteen pts (42%) discontinued sorafenib before completing paclitaxel (mean time on sorafenib 3.7 weeks; &lt;1 week in 18% of all pts). 9 of these 19 pts (47%) stopped sorafenib due to symptoms. Grade (G) 3/4 non-hematologic toxicity during sorafenib therapy in &gt;5%: arthralgias/myalgias, neuropathy, pain, and pulmonary symptoms (8% each), and rash (11%). G3/4 hematologic toxicity during sorafenib treatment was limited to neutropenia in 11%. There were no sorafenib-related deaths. Discussion: In this pilot study, sorafenib was generally associated with limited severe toxicity when combined with paclitaxel following AC. However, many pts discontinued sorafenib early suggesting sequential scheduling may be more feasible than concurrent administration with chemotherapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2110.
Preliminary toxicity results of a phase II trial of adjuvant docetaxel/cyclophosphamide plus trastuzumab in HER2+ early stage breast cancer patients.
Authors: Jones SE , Collea RP , Oratz R , Paul D , Sedlacek SM , Holmes FA , Portillo RM , Crockett MW , Asmar L , O'Shaughnessy JA , Robert NJ 
Published: December 2010

Abstract
Abstract #2111
Background: Docetaxel/cyclophosphamide (TC) has demonstrated superior activity to doxorubicin/cyclophosphamide (AC) in the adjuvant treatment of patients (pts) with early breast cancer and is devoid of known cardiac toxicity (Jones et al, SABCS 2007, abstract 12). Although the addition of trastuzumab (H) to anthracycline-based adjuvant regimens has proven effective, it has also been associated with increased cardiac toxicity. Therefore, a short course of the nonanthracycline TC regimen coupled with H appeared to be a logical combination for women with lower risk HER2+ breast cancer. We report safety and tolerability of the TC+H regimen.&#x2028; Patients and Methods: 256 of a planned 260 patients (pts) were registered to the study and stratified by positive or negative nodes. On Day 1 of each 21-day cycle for a total of 4 cycles, pts received (in order): (T) 75 mg/m2 IV, followed by (C) 600 mg/m2 IV. Weekly (H) was also given at 4 mg/kg IV (loading dose, over 90 minutes Day 1, Cycle 1 only) and 2 mg/kg IV (Days 1, 8, 15) thereafter throughout chemotherapy. After completion of chemotherapy, H was administered at a dose of 6 mg/kg IV every 3 weeks to complete 12 months of therapy with H. Pts must have had LVEF &gt;50% at the time of registration and had regular cardiac evaluation throughout the study (MUGA or ECHO).&#x2028; Results: To date, 231 pts were treated and comprise the safety population; this first report focused on toxicity occurring during the first 4 months of co-administration of chemotherapy and H. The median age was 55 years; 84% of pts were ECOG 0; 61% were ER+. Selected treatment-related toxicities in ≥3% of pts are listed in Table 1. Of the 231 pts, 10 pts came off treatment due to adverse events: hypersensitivity (3), gastrointestinal (2), hematologic (2), pulmonary (1), skin (1), and cardiac (1). To date, only 1 patient has had a significant drop in LVEF to 40%, and was taken off treatment.&#x2028; &#x2028; Conclusion: 4 cycles of TC combined with H is a well-tolerated adjuvant treatment with an acceptable toxicity profile for lower risk patients with HER2+ breast cancer.&#x2028; This research was supported, in part, by a research grant from sanofi-aventis, Bridgewater, NJ.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2111.
The number needed to treat (NNT) as a measure of drug efficacy: the case of zoledronic acid for early hormone-responsive breast cancer in the ABCSG-12 trial.
Authors: Gnant M , Mlineritsch B , Schippinger W , Luschin-Ebengreuth G , Steger G , Bjelic-Radisic V , Jakesz R , Kubista E , Marth C , Greil R ,   on Behalf of the Austrian Breast and Colorectal Cancer Study Group
Published: December 2010

Abstract
Abstract #2113
Background: Zoledronic acid (ZOL) has demonstrated antitumor and antimetastatic activities in preclinical and early clinical studies in many cancer types. The Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12) examined the efficacy of adjuvant therapy in premenopausal women with hormone-responsive early breast cancer receiving goserelin (GOS) + anastrozole (ANA) or tamoxifen (TAM), both ± ZOL. In this trial, ZOL significantly prolonged disease-free survival (DFS) and recurrence-free survival (RFS) versus no ZOL. However, in addition to relative risk reduction, the potential for patients to benefit from a treatment is an important consideration. The number needed to treat (NNT) represents an estimation of the number of patients that have to be treated with an investigational drug for 1 patient to receive clinical benefit within a specific follow-up period. NNT is a powerful, clinically relevant measure of efficacy that can provide a real-world perspective on the efficacy results from clinical trials. Methods: 1,803 patients were randomized to GOS (3.6 mg/28 d SC) + TAM (20 mg/d PO) ± ZOL (4 mg/ 6 mos IV) or GOS + ANA (1 mg/d PO) ± ZOL for 3y. Endpoints at 60 mos for TAM vs ANA and ZOL vs no ZOL were DFS (primary), RFS, overall survival and safety. NNT was calculated for ZOL with respect to DFS and RFS, and compared with other paradigm-changing cancer therapies. Results: After 60 mos median follow-up, ZOL significantly reduced the risk of DFS events by 36% (P = .01) and RFS events by 35% (P = .02) vs no ZOL. For ZOL therapy, NNT = 31 and NNT = 33 to prevent 1 DFS or 1 RFS event respectively at a median follow-up of 60 months. In comparison, the NNT with respect to DFS is 28 for paclitaxel (60-69 months follow-up) and 31 for docetaxel (43-60 months follow-up). Moreover, ZOL was generally well tolerated, and neither ONJ nor renal toxicity was an issue in this setting. Conclusions: The NNT is a simple and effective method to assess clinical trial results that will have relevance to daily practice. In the current comparisons, the NNT for ZOL plus endocrine therapy in ABCSG-12 was similar to the NNTs for taxanes. Therefore the addition of ZOL provides DFS and RFS benefits of magnitudes similar to those from practice-changing chemotherapies like taxanes.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2113.
Ligand-mediated selective targeting of adenovirus in metastatic breast cancer.
Authors: Stoff-Khalili MA , Bhatia S , Odaka Y , Li XL , Podduturi J , Smart L , Mallmann P , Schmutzler RK , Curiel DT , Mathis MJ 
Published: December 2010

Abstract
Abstract #2126
The success of gene therapy relies on efficient and targeted delivery systems. Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their tendency to induce liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many solid tumors (e.g., colon, lung, and breast) and hematopoietic tumors over express the chemokine receptor CXCR4. CXCR4 belongs to the large superfamily of G protein-coupled receptors, and is known to participate in a number of biological processes including organogenesis, hematopoiesis, and immune response. Recent evidence has highlighted the role of CXCR4 in cancer, particularly in cancer metastasis due to dysregulation of the receptor leading to enhanced signaling. The present study addresses this issue by retargeting adenovirus to the breast cancer cells overexpressing CXCR4 receptor. We used sCAR-T4-CXCL12, a bispecific adaptor molecule with the ectodomain of CAR linked by the T4 fibritin trimerization motif to the human CXCR4 ligand CXCL12 (also known as SDF-1). The sCAR-T4-CXCL12 should therefore be useful in retargeting adenovirus vectors to CXCR4-positive metastases. Infectivity assays in the absence as well as presence of ligand were performed in human breast cancer MDA-MB-435 cells. Cells were infected with different titres of Ad-CMV-GFP-Luc with and without ligand. Forty-eight hours post-infection, cells were harvested and analysed for the GFP expression by fluorescent microscopy and flow cytometry. It was further interesting to observe the time-dependence of infectivity curve. For this purpose, MDA-MB-435 cells were incubated with optimum titre of Ad-CMV-GFP-Luc vector in the presence of CXCR4 targeting ligand at different time intervals. This was followed by expression analysis of GFP protein by fluorescent microscopy and flow cytometry. Quantification by flow cytometry demonstrated a dramatic 20- to 40-fold increase in the infectivity of MDA-MB-435 cells both in a dose-dependent and time-dependent manner using the sCAR-T4-CXCL12 targeted adenovirus compared to the untargeted vector. In this report, we show that sCAR-T4-CXCL12 can significantly redirect an adenoviral gene therapy vector to CXCR4-positive breast cancer cells in culture. This bispecific ligand should, therefore, be a powerful agent to retarget adenovirus vectors to tumor metastases. The future goal is to investigate the capacity of this agent to re-direct adenoviral vectors in vivo using breast cancer metastasis models.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2126.
Effective tumor growth inhibition of MX1 and MDA-MB-231 estrogen receptor negative human breast cancer xenografts by treatment with LHRH antagonist cetrorelix.
Authors: Seitz S , Schally AV , Papadia A , Glueck S , Calfa C , Ortmann O , Buchholz S 
Published: December 2010

Abstract
Abstract #2137
Introduction&#x2028; Agonists of LHRH are a treatment option in premenopausal women with estrogen receptor positive breast cancer. The treatment with those agonists decreases the levels of FSH and LH in the blood and thus reduces the levels of sex hormones. Patients with estrogen receptor negative breast cancers do not benefit from therapy with LHRH agonists. Antagonists of LHRH lower LH, FSH and sex steroid levels but without the initial flare up of FSH and LH. In addition to the endocrine effects, Cetrorelix also shows a direct inhibition of cell growth in LHRH receptor (LHRH-R) positive gynecological cancer in vitro where alterations of FSH, LH and sex hormone levels are clearly excluded. In view of these findings we decided to investigate Cetrorelix on the tumor growth in two estrogen receptor negative but LHRH-R positive breast cancer cell lines.&#x2028; Materials and Methods&#x2028; The mRNA expression of LHRH-R was detected by PCR. For proliferation assays cells were treated with increasing doses of Cetrorelix acetate in 0.5% FBS supplemented RPMI 1640 media. MTS assays were performed after 72h. Fluorescence microscopy using ethidium bromide staining was performed to show cell death. In the in vivo study, nude mice were treated with Cetrorelix pamoate preparation at a dose of 3mg s.c. releasing an estimated 100mg Cetrorelix/day.&#x2028; Results&#x2028; MX1 and MDA-MB-231 estrogen receptor negative human breast cancer cell lines were positive for the expression of mRNA for LHRH-R. The cell proliferation in vitro of MX1 and MDA-MB-231 lines treated with different concentrations of Cetrorelix was significantly inhibited in a dose dependent manner. Time and dose dependent cell death was observed by fluorescence staining. Experimental treatment in vivo with Cetrorelix pamoate preparation reduced a significant inhibition of tumor growth in MX1 xenografts as compared to the Controls after 14 days and the suppression remained significant until the end of the study on day 28. MDA-MB-231 xenografts treated with Cetrorelix also showed a significant inhibition of tumor growth compared to the Control as early as day 7 and the inhibition remained significant until the end of the study on day 28.&#x2028; Conclusion&#x2028; Our results indicate a direct inhibitory effect of Cetrorelix on LHRH-R positive breast cancers. Since LHRH-R are expressed in ER negative breast cancers, these findings suggest a new approach to the treatment of LHRH-R positive breast cancer patients independent of the estrogen receptor status.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2137.