bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PD08-08: Exercise for Health: A Randomised, Controlled Trial of an Exercise Intervention for Women with Breast Cancer — Effect on Upper-Body Function
Authors: Hayes SC , Rye S , Eakin E , Battistutta D. 
Published: April 2011

Abstract
Background: Impairments in upper-body function are common during and following breast cancer and may persist into long-term survivorship. An objective of the Exercise for Health program was to assess the effect participation in an 8 month exercise program (initiated 6 weeks after breast cancer surgery) has on upper-body function and associated symptoms.
Methods: Women residing in an Australian metropolitan city and diagnosed with invasive breast cancer were eligible to participate in this randomised, controlled trial. Consenting women were allocated to either a face-to-face delivered exercise group (FG, n=67), a telephone-delivered exercise group (TG, n=67) or a usual-care group (UG, n=60). At 6 weeks (pre-intervention), 6 months (mid-intervention) and 12 months (postintervention) after surgery upper-body function was assessed via self-report using the Disability of the Arm, Shoulder and Hand questionnaire and clinically using an incremental maximal upper-body strength test. The presence and severity of upper-body symptoms such as pain, weakness and numbness were assessed using a 5-point Likert scale, while lymphoedema was measured clinically using bioimpedance spectroscopy.
Results: Women in the exercise intervention groups reported greater improvements (p=0.02) in perceived upper-body function (indicated by negative scores) between 6 weeks and 6 months post-surgery, (FG, mean=-6.3; TG, mean=-11.9) when compared to changes observed in the UG (mean=-4.2) and maintained these improvements by 12-months PS. Similar findings were observed for clinically measured upper-body function (P&lt;0.01). At 12 months post-surgery, those in the UG were 1.5 times more likely to report at least one moderate to severe upper-body function symptom. The number of lymphoedema cases did not differ between the groups at mid-or post-intervention.
Discussion: These results demonstrate that exercise interventions, delivered over the phone or face-to-face, can facilitate improvements in upper-body function during and following breast cancer treatment without adversely increasing risk of developing lymphoedema or other arm-related symptoms. This is particularly important since function is directly associated with a woman's ability to carry out daily tasks and has been shown to predict quality of life.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-08.
Abstract PD10-04: An ERBB2 Gene Dosage Effect Confers Biological Aggressiveness to Breast Cancers and Trastuzumab Sensitivity in Patients with Metastatic Disease
Authors: Fuchs E-M , Köstler WJ , Horvat R , Hudelist G , Kubista E , Zielinski CC , Singer CF. 
Published: April 2011

Abstract
Background: Despite patient selection based on ERBB2 overexpression, response to trastuzumab-based therapy is not always achieved. The reasons for response failure to ERBB2-targeted therapy are still largely unknown. We have investigated whether a gene dosage effect, conferred by an increased number of ERBB2 copies, might provoke increased biological aggressiveness and altered trastuzumab sensitivity. Methods: Vysis PathVysion DNA-based FISH technology was used to measure absolute ERBB2 copy numbers (“CN”) and ERBB2/centromer 17 ratios (“R”) in tumor specimens of 137 patients who had received trastuzumab-based treatment for Her-2/neu over-expressing metastatic breast cancer.
Results: An R of &gt; 2.2 was identified as independent negative predictor for time to first metastasis (TTM). Upon trastuzumab-initiation, progressionfree survival (PFS), albeit not overall survival (OS), was significantly longer in patients with R of ≥2.2 (p=0.006 and p=0.123, respectively). Within the amplified patient population a CN &gt; 13 (“high-amplified”) predicted for a significantly shorter TTM and, upon trastuzumab-initiation, a significant longer PFS and showed a trend towards a higher OS (p= 0.020 and p=0.086, respectively; Log Rank test) compared with the low-amplified (CN ≥13) patient population. Multivariate Cox regression analysis revealed that within our patient population higher CN and R were both associated with improved PFS (p=0.003 and p=0.004, respectively) and OS (p=0.004 and p=0.038, respectively).
Furthermore, Logistic Regression analysis showed that higher CN and R values were associated with improved overall responses (OR: 1.151, 95% CI: 1.034-1.269 and OR: 1.501, 95% CI 1.169-1.964, respectively). Conclusion: In ERBB2 over-expressing FISH-amplified breast cancers CN can discriminate between two groups of breast cancer patients with different prognosis in the adjuvant setting as well as in the metastatic setting under the influence of trastuzumab-based therapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD10-04.
Abstract PD10-05: Do the Results of Metastatic Breast Tumour Biopsies Affect Patient Survival Outcomes? Results from a Large Prospective Trial
Authors: Amir E , Miller N , Geddie W , Maung H , Freedman OC , Oldfield M , Napolskikh J , Kassam F , Simmons C , Clemons M. 
Published: April 2011

Abstract
Background: Differences in receptor status between primary and metastatic breast cancer are well recognized. We have previous demonstrated substantial receptor discordance rates resulting in a change in management in 14% of patients. However, while retrospective studies suggest that discordance can be associated with a worse patient prognosis, there are currently no prospective data assessing the impact of such discordance on survival outcomes.
Methods: A single-center prospective biopsy study was performed. Patients with either recurrent or progressive disease underwent biopsy of their metastases. Subsequent treatment choices were modified according to the results and patients were followed up for progression or death. To account for the differing times at which patients entered the study, progression-free survival (PFS) was calculated as the duration between biopsy and either progression or death. Overall survival (OS) was defined as the duration from diagnosis of metastatic disease to death. A Cox propotional hazards model accounting for duration of metastatic disease and visceral versus non-visceral metastatic disease was utilized.
Results: 121 biopsies were completed and 38% of cases showed discordance between the primary and the recurrence. Survival data were available from 96 patients. After a median follow-up of 11 months, 76 patients (79%) had progressed and 38 (40%) had died. There was no difference in median PFS between concordant and discordance cases (5.9 vs. 6.5 months, HR 0.89, p=0.61). There was a non-significant trend towards worse OS in discordant cases (50.6 vs. 57.8 months, HR 0.77, p=0.47). When compared with the primary tumour a gain of HER2 was associated with a poor survival, while loss of HER2 was associated with improved outcome. Metastatic biopsies showed a trend towards better prediction of response to endocrine therapy with tumors losing progesterone receptor expression between primary and metastatic disease having worse DFS on endocrine therapy. Conclusion: We have previously shown that performing metastatic biopsies is associated with a substantial rate of receptor discordance between primary and metastatic disease. The current analysis demonstrates that this discordance is associated with a trend towards worse OS, but not PFS. Knowledge of the receptor status of metastatic disease allows better prognostication between HER2-postive and HER2-negative disease and also allows for improved prediction of response to endocrine therapy. Metastatic biopsies should therefore be considered in patients with recurrent breast cancer.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD10-05.
Abstract S1-4: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of AMG 479 With Exemestane (E) or Fulvestrant (F) in Postmenopausal Women With Hormone-Receptor Positive (HR+) Metastatic (M) or Locally Advanced (LA) Breast Cancer (BC)
Authors: Kaufman PA , Ferrero JM , Bourgeois H , Kennecke H , De Boer R , Jacot W , McGreivy J , Suzuki S , Loh E , Robertson J. 
Published: April 2011

Abstract
Background: AMG 479 is an investigational, fully human monoclonal antibody targeting the type 1 insulin-like growth factor receptor (IGF1R) that blocks binding of IGF-1 and IGF-2. Preclinical data suggest that inhibition of estrogen receptor (ER) and IGF1R signaling in ER+ BC can result in greater suppression of cell proliferation than achieved by blocking either pathway alone. Inhibition of the IGF1R-signaling pathway might enhance sensitivity of 2nd-line hormonal therapy in BC patients (pts). We conducted a 2-arm, double blind, placebo-controlled, randomized study evaluating the addition of AMG 479 to either E or F in M or LA BC pts who had progressed on prior endocrine therapy.
Patients: Eligibility included: HR+ incurable M or LA BC; progression while receiving prior endocrine therapy for MBC or LA or within 12 months of completing adjuvant hormonal therapy; post menopausal; adequate glycemic control. HER2+ tumor status allowed. Study Design: Pts were randomly allocated 2:1 to either AMG 479 or placebo; E or F was per investigator. Pts received AMG 479 12 mg/kg IV or placebo Q2W + either E 25 mg QD PO or F 500 mg IM on day 1, 250 mg IM day 15 and 29, and Q4W thereafter. Eligible pts who progressed on the placebo arm could proceed on open-label AMG 479. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death. MRI or CT scans were done every 8 weeks and bone scans every 12 weeks (for pts with bone involvement at screening).
Endpoints: The primary endpoint was progression-free survival (PFS), as measured by modified RECIST v1.0 per investigator review.
Results: 156 pts were randomized between March 2008 and July 2009. Median age, 61 (range 36-88) years; M vs LA BC, 154 (99%) vs 2 (1%). 127 pts (81%) had discontinued treatment as of May 2010. See table for efficacy. For pts receiving AMG 479 or placebo, the incidence of grade ≥3 AE was 42% and 24% and for serious AE, 25% and 18%. The most common grade ≥3 AEs (AMG 479/placebo) were: hyperglycemia (6%/0%), neutropenia (6%/2%), thrombocytopenia (4%/0%), asthenia (4%/2%), and increased AST (4%/0%). There were 5 grade 5 AEs; none were treatment related: 4 in the AMG 479 arm (2 PD, 1 sub occlusive syndrome [progression], and 1 pulmonary embolism [post-operative setting]) and 1 in the placebo arm (alteration of general status). 8% of pts in the AMG 479 arm vs 12% in the placebo arm had AEs that led to discontinuation of any study treatment.
Conclusion: The combination of AMG 479 + E or F did not result in an improvement in PFS in this population of pts with HR+ M or LA BC. There were no unanticipated safety findings.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-4.
Abstract S1-5: Interaction between Goserelin and Tamoxifen in a Controlled Clinical Trial of Adjuvant Endocrine Therapy in Premenopausal Breast Cancer.
Authors: Sverrisdottir A , Johansson H , Johansson U , Bergh J , Rotstein S , Rutqvist LE , Fornander T. 
Published: April 2011

Abstract
Background: Ovarian ablation improves survival in premenopausal women with early breast cancer, but the potential added value by luteinizing hormone-releasing hormone agonists (LHRH-a) to tamoxifen, is still not clear. There has been lack of data reported separately for patients who underwent randomization to both LHRH-a and tamoxifen. Patients and Methods: In Stockholm, 927 patients assigned to the Zoladex in Premenopausal Patients (ZIPP) trial, were included in a 2 x 2 factorial randomization to goserelin (3.6 mg subcutaneously, q 28d), tamoxifen (40 mg daily), the combination of goserelin and tamoxifen or no endocrine therapy for two years, with or without chemo-and/or radiotherapy. The trial was designed to examine the effect of goserelin and the role of interaction between goserelin and tamoxifen in adjuvant therapy of premenopausal breast cancer. We examined as well, the impact of different estrogen receptor (ER) content on treatment effect. The definition of first event was breast cancer recurrence, contra lateral breast cancer or death. The ER content was determined by isoelectric focusing on polyacrylamide gel and receptor values normalized to DNA content.
Results: After a median follow up of 12.3 years, goserelin reduced the risk of first event by 32% (p=0.005) in the absence of tamoxifen and tamoxifen reduced the risk by 27% (p=0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24% (p=0.021) and there was a significant interaction between goserelin and tamoxifen (p=0.025). In highly ER positive tumours, there were 29% fewer events among goserelin treated (p=0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, p=0.007). For tamoxifen, there was not a significant risk reduction at different ER levels, but there was a trend towards interaction between goserelin and tamoxifen effect among the highly ER positive (p=0.076).
Discussion: In this strictly randomized cohort of endocrine responsive premenopausal breast cancer, goserelin as well as tamoxifen, reduces the risk of recurrence. However, the combination of goserelin and tamoxifen is not superior to either modality alone. The effect of goserelin seems to be modified by ER levels, whereas tamoxifen effect is not. Women with strongly estrogen receptor positive tumours may benefit more from goserelin treatment.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-5.
Abstract S1-7: Lack of Correlation between Gene Variants in Tamoxifen Metabolizing Enymes with Primary Endpoints in the ATAC Trial.
Authors: Rae JM , Drury S , Hayes DF , Stearns V , Thibert JN , Haynes BP , Salter J , Pineda S , Cuzick J , Dowsett M. 
Published: April 2011

Abstract
Background. A number of studies have provided widely heterogeneous results for and against the hypothesis that genetic variants in drug metabolizing enzymes can influence patient response to tamoxifen. Most of these studies are confounded by relatively small numbers of patients, lack of comprehensive genotype information, lack of detailed clinical outcome data, and patient selection biases. The ATAC trial was a prospective randomized double-blind placebo-controlled trial designed to compare the adjuvant use of anastrozole versus tamoxifen for 5 years. The trial's detailed efficacy and safety data, long term (10-year) follow-up and high number of events make it an ideal setting for pharmacogenetic analyses. Here we report our initial findings testing for correlations with SNPs in CYP2D6 and UGT2B7, the primary enzymes responsible for the presumed activation and inactivation of tamoxifen, respectively, with clinical outcomes including any disease recurrence, distant recurrence, and overall survival.
Methods: CYP2D6 genotype data for the 7 most common alleles were used to assign each patient a ‘score’ based on predicted allele activities from 0 (no activity) to 2 (high activity). Patients were also tested for the UGT2B7*2 variant, which has lower enzymatic activity and has been shown to correlate with higher serum endoxifen concentrations. All genotype determinations were made without knowledge of the patient's treatment assignment or outcomes.
Results: Comprehensive CYP2D6 genotype data were obtained on 588 and 615 patients randomized to receive tamoxifen, and anastrozole, respectively. After median 10 years of follow-up, there were 115 recurrences in the tamoxifen cohort. We found no associations between any of the CYP2D6 scores and rates of recurrence in tamoxifen treated patients. A test for trend across CYP2D6 scores was not significant. In the anastrozole cohort, there were 92 recurrences, and there was no evidence of an association between CYP2D6 score with rates of recurrence. Likewise, there was no detectable association in either the tamoxifen or anastrozole group with UGT2B7 genotype alone or in combination with CYP2D6 score. Concomitant SSRI usage was recorded in these patients and is being assessed for possible impact on these results.
Conclusion: These data from a large prospective clinical trial, with detailed outcome data and long-term follow-up do not support the hypothesis that patient with decreased CYP2D6 enzymatic activity receive less benefit from tamoxifen therapy compared to wild-type CYP2D6 patients. Variants in drug targets and estrogen signaling pathways may be the genetic basis for patient variability in anti-estrogen risk versus benefit profiles.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-7.
Abstract S2-1: Obesity at Diagnosis Is Associated with Inferior Outcomes in Hormone Receptor Positive Breast Cancer
Authors: Sparano JA , Wang M , Martino S , Jones V , Perez EA , Saphner T , Wolff AC , Sledge GW , Wood WC , Fetting J , Davidson NE. 
Published: April 2011

Abstract
Background: Obesity has been associated with worse outcomes in operable breast cancer. We evaluated the effect of obesity on outcomes in several adjuvant trials coordinated by the ECOG which included doxorubicin/cyclophosphamide plus other agents, including E1199 (NEJM 2008; 358: 1663), E5188 (JCO 2005; 23: 5973) and E3189 (JCO 10998; 16: 2382). Methods: The relationship between body mass index (BMI in kg/m2) and disease free survival (DFS) and overall survival (OS) was evaluated in multivariate models adjusted for covariates including age, tumor size, nodal status, race (black vs. other), surgery type, prior RT, menopausal status, treatment arm, and treatment adherence. Results are expressed as hazard ratios (HR) from Cox's proportional hazards models (HR &gt; 1 indicates a worse outcome). All p-values are two sided.
Results: The study characteristics and results are shown in the table below. We first evaluated results for the E1199 trial (for the 75% of those with BMI data available) and found a non-significant trend toward inferior DFS (HR 1.10, 95% CI 0.96, 1.26, p=0.18) and OS (HR 1.13, 95% CI 0.96, 1.33, p=0.15) for obese subjects compared with others. When evaluated by breast cancer subtype, however, obese subjects with ER and/or PR-positive/HER2-negative disease had significantly inferior DFS (HR 1.24, p=0.026) and OS (HR 1.42, p=0.003), an effect that was not seen for HER2-positive and triple negative disease. In a model including obesity, ER and/or PR-pos/HER2-neg disease, and their interaction, the interaction term was significant for OS (p=0.017) but not DFS (p=0.21). There was no evidence for differing chemotherapy delivery or endocrine therapy adherence, or differences in toxicity for obese subjects in the E1199 trial. We then evaluated the relationship between obesity and outcomes in two prior ECOG studies which included only premenopausal women with ER positive, node positive breast cancer (E5188) and women of any age with ER/PR negative, node positive disease (E3189), and confirmed a relationship between obesity and poor outcomes only in women with hormone receptor positive disease.
HR-hazard ratio; ER/PR-estrogen/progesterone receptor
Conclusions: Obesity was associated with significantly inferior DFS and OS in hormone receptor positive operable breast cancer treated with adjuvant chemotherapy. These findings suggest that hyperinsulinemia or other factors associated with obesity may predispose to recurrence specifically in hormone receptor positive disease, and requires further evaluation in prospective studies in order to identify modifiable factors contributing to this effect.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-1.
Abstract S2-2: Multivariate Analysis of Obesity and Disease Free Survival in Patients with Nodal Positive Primary Breast Cancer — The ADEBAR Trial
Authors: Hepp PGM , Rack B , Annecke K , Wischnik A , Wolfgang S , Zwingers T , Harbeck N , Sommer HL , Friese K , Kiechle M , Janni W. 
Published: April 2011

Abstract
Background: The prevalence of obesity increases throughout all evolved civilizations. On the other hand several epidemiological studies have shown not only an increase in breast cancer among obese women but also an adverse impact of obesity on survival of breast cancer patients. This analysis focuses on the impact of obesity on patients (pts) treated within the ADEBAR study protocol.
Methods: The ADEBAR Trial compared 4 cycles of EC followed by 4 cycles of Doc vs. 8 cycles of FEC (120) in pts with primary breast cancer (&gt;=4LN). 1500 pts have been accrued from sep/01 through may/05. For this analysis data of 1361 pts has been analyzed about the impact of obesity on disease free survival. Therefore pts have been grouped to either “underweight” (BMI&lt;18.5kg/m2), “normal weight” (BMI18.5-25kg/m2), “overweight” (25kg/m2&lt;BMI&gt;30kg/m2) or “obese” (BMI&gt;30).
Results: 13 pts (1.0%) were “underweight”, 557 pts (40.9%) were normal weight, 491 pts (36.1%) were overweight, 300 pts (22.0%) were obese at the time of study enrollment. After a follow up period of 60 months 87.5% of the underweight group, 70.4% of the normal weight group, 70.7% of the overweight group and 58.6% of the obese group were alive with no signs of recurrent disease. This difference was significant (Chi-square=9.355; p&lt; 0.0249). The tumor size at clinical diagnosis was strongly associated to the patient's weight (&lt; 0.0001). There was no significant difference in the number of positive lymph nodes (p = 0.2890), tumor histology (p = 0.9750), grading (p = 0.9520), ER and PR hormone receptors (ER p = 0.9708, PR p = 0.7785) and the expression of HER2 (p = 0.1710) regarding underweight, normal, overweight and obese patients. In a multivariate analysis obesity was an independent prognostic factor with a hazard ratio of 1,007 per 1kg/m2 increase (P&lt;0,0167).
Conclusion: This analysis strongly implicates an impact of obesity on disease free survival in patients with early stage node positive breast cancer in the prospectively randomized ADEBAR multicenter trial. It is therefore in line with earlier findings in epidemiological research and raises the question whether a weight reduction might be an additional approach on breast cancer therapy. Figures available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-2.