bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P5-09-01: Improving Informed Consent: Evaluating the First Decision Aid in a Clinical Trial Setting (IBIS-II Breast Cancer Prevention Trial)
Authors: Juraskova I , Butow P , Smith B , Seccombe M , Coates A , Boyle F , McCarthy N , Reaby L , Forbes JF. 
Published: April 2011

Abstract
Background: Recruitment to clinical trials is generally suboptimal, with both patients/consumers and clinicians reporting difficulties with the consent process. Decision Aids (DAs) are designed to facilitate doctor-patient communication and participation in decision-making, and may improve the consent process by ensuring patients/consumers make decisions that are informed and acted upon. While participant information sheets (PIS) provide information about the specific clinical trial, DAs present evidence-based information about all available management options (not just the clinical trial), including risks and benefits of each option. They also present both written and graphical forms of the information to enhance understanding, and explicit value clarification exercises to facilitate value-sensitive decisions. In screening and treatment settings, DAs have been found to reduce decisional conflict, improve patient knowledge, create more realistic expectations, and promote active decision-making without increasing anxiety. This RCT aimed to evaluate the efficacy of a DA for women at increased risk of breast cancer who are considering participation in the IBIS-II Prevention trial.
Methods: Women eligible for IBIS-II, who had not decided about participation, were invited to take part in the DA study. Participants from 12 Australian and New Zealand IBIS-II centres were randomised to receive either the standard IBIS-II information and consent materials alone (Control group, n=89), or in combination with a DA booklet (DA group, n=89). Participants completed standardised and purpose-designedmeasures 1 week and 3 months after deciding whether or not to participate in IBIS-II.
Results: In the Prevention arm, the majority of women (84%) reported the DA made it easier to understand IBIS-II compared to reading the PIS alone, and 89% recommended providing both the DA and PIS to potential IBIS-II participants. No group differences were detected in levels of decisional conflict or knowledge of IBIS-II/clinical trials in general, due to floor and ceiling effects respectively. Similarly, no group differences were found in levels of decisional regret and satisfaction at 3-month follow-up. Discussion: This is the first study to assess the effectiveness of DAs in a clinical trial setting. The use of DAs has been strongly endorsed by participating women and clinicians. Challenges of evaluating DAs in a Prevention breast cancer trial setting will be discussed. An RCT of a DA for the DCIS arm of IBIS-II is currently underway. The DAs have the potential to enhance the process of informed consent and reduce dropout rates in clinical trials.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-09-01.
Abstract P5-10-02: Clinical Outcome of Two Sequences of Administering Paclitaxel (P) and Anthracyclines (A) as Primary Systemic Therapy (PST) and Adjuvant Chemotherapy (ACT) in Breast Cancer (BC) Patients: A Retrospective Analysis from the M. D. Anderson Cancer Center (MDACC)
Authors: Alvarez RH , Bianchini G , Hsu L , Cristofanilli M , Esteva FJ , Pusztai L , Buzdar AU , Hortobagyi GN , Valero V. 
Published: April 2011

Abstract
Background: P-and A-based regimens are widely used as PST and ACT of early BC. It is unknown whether the efficacy of such combinations is affected by their sequence of administration. The purpose of this retrospective analysis was to assess the clinical outcome of two different sequences of P and A in pts receiving PST and ACT.
Methods: We analyzed 3,010 pts (1,414 PST and 1,596 ACT) with stage I — III BC treated between 1994 -2009. These pts were identified through our prospective online MDACC breast cancer database. Pts treated with trastuzumab, docetaxel or adriamycin/cyclophosphamide-regimen were excluded. Pathological complete response (pCR) was defined as no residual invasive disease in breast and ipsilateral axillary lymph nodes.
Results: PST cohort included 1.071 pts (75%) with clinical stage I-IIIA and 343 (24.2%) stage IIIB-IIIC BC; 1,188 pts (84%) received the sequence P→A and 226 pts (16%) A→P. In the PST cohort 958 pts (67.7%) and 161 (11.3%) had hormone-receptor (HR) positive (+) and HER-2 + BC, respectively. ACT cohort consisted of 1,503 pts (94%) with pathological stage I-IIIA and 93 (5.82%) stage IIIB-IIIC. 1,196 pts (75%) received the sequence P→A, and 400 pts (25%) A→P. In the ACT cohort 1,122 (70.3%) and 93 (3.9%) had HR+ and HER2+ BC, respectively. Both cohorts of pts were balanced by HR-status, clinical stage, and menopausal status. The combined p-values for ACT and PST cohorts were calculated and they were significant for both RFS (p=0.022) and OS (p=0.002). In univariate analysis the sequence A→P was associated with inferior outcome. In Cox multivariate analysis, after stratification for period at diagnosis and adjustment for age, clinical stage, HR status, grade, and LVI the A→P sequence administered as PST was associated with significantly higher risk of relapse (HR 1.49; CI 1. 10-2.03; p=0.01) but not death (HR 1.28; CI 0.90-1.84; p=0.17). In the ACT cohort, the Cox multivariate analysis, after stratification for age, HR status, HER2 the sequence A→P was significantly associated with higher risk of death (HR 2.02; CI 1.33-3.06; p=0.001) but not relapse (HR 1.21; CI 0.82-1.79; p=0.33).
Conclusions: The P→A sequence compared to the A→P sequence is associated with lower risk of relapse and death in PST and ACT, respectively. This retrospective analysis is hypothesis-generating and should lead to a prospective randomized trial to compare the two sequences as PST or ACT in locally advanced or early BC, respectively.
Primary Systemic Therapy (N=1,414)

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-02.
Abstract P5-10-11: Ongoing Evaluation of Capecitabine-Based Therapy in Early Breast Cancer (EBC)
Authors: Poole C , Barrios C , O'Shaughnessy J , Martin M , Möbus V. 
Published: April 2011

Abstract
Background: Capecitabine (C) is an established agent in MBC & is being evaluated in anthracycline/taxane-based adjuvant (adj) & neoadjuvant (neoadj) regimens.
Methods: We summarise available data for C from randomised phase III studies in EBC.
Results: Significant efficacy benefits were reported with two C-based regimens in EBC: recurrence-free survival (RFS) was significantly improved when C was added to an adj regimen in the FinXX trial (3-year RFS: 93% vs 89% control; HR 0.66 [95% CI: 0.47-0.94]; p=0.02) [Lancet Oncol 2009;10:1145-51]. Pathological complete response (pCR) was significantly higher when C was integrated into a standard neoadj regimen in the ABCSG-24 study (24.3% vs 16.0% control; p=0.02) [ECCO-ESMO 2009; Abst 4BA]. Two studies were negative: one adj [Muss et al. NEJM 2009;360:2055-65] & one neoadj [GeparQuattro JCO 2010;2024-31].
D=docetaxel; Cyc=cyclophosphamide; E=epirubicin; F=5-FU; A=doxorubicin; P=paclitaxel; bev=bevacizumab; G=gemcitabine; M=methotrexate; DFS=disease-free survival; EFS=event-free survival
Safety data are available from 3 other adj studies: in the GEICAM trial, ED→C was generally well tolerated and associated with significantly better hair recovery than control (incomplete hair recovery: 28% ECyc→D vs 11% ED→C; p=0.0004); in the GAIN study, haematological toxicities were more common in the E→P→Cyc arm & discontinuations more frequent with ECyc→CP; in the ICE study in pts aged &gt;65 yrs, a low incidence of grade 3/4 AEs was reported with C & significantly higher global QoL scores were attained with C vs control (week 20, p=0.008). Several phase III trials are ongoing (table): US Oncology is conducting a study in high-risk EBC, which will report efficacy data shortly; CIBOMA collaborative group is conducting a trial of C maintenance therapy after adj anthracycline/taxane in triple-negative EBC; the TACT2 study has a 2x2 factorial design in resected/operable EBC; safety data are expected from both studies: MINDACT is an EORTC/collaborative group study in node-negative EBC and compares a 70-gene signature with traditional methods of risk evaluation; pts with high-risk disease receive anthracyclines or CD.
Conclusions: The ongoing evaluation of C in EBC encompasses &gt;20,000 pts. Following initial positive data for C in EBC, further results of these trials are eagerly awaited to define the clinical utility of C-based therapy in this setting.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-11.
Abstract P5-10-13: Phase I Dose Escalation Study of Pirarubicin in Combination with Cyclophosphamide in Breast Cancer
Authors: Sakata M , Jinno H , Hayashida T , Takahashi M , Sato T , Seki H , Shimada K , Nishiya S , Kitagawa Y. 
Published: April 2011

Abstract
Background: Doxorubicin containing combination chemotherapy regimens are widely used for treatment of breast and other cancers. However, these regimens are associated with significant toxicities including myocardialdysfunction and alopecia. Analogues of doxorubicin are being developed to reduce these side effects. Pirarubicin is a more lipophilic derivative of doxorubicin, with a higher uptake rate of cells, lower cardiotoxicity and better antitumor efficacy in preclinical models.
Purpose: We conducted a single-institution phase I clinical trial to determine the maximum-tolerated dose (MTD) and define the toxic effects and recommended dose (RD) of pirarubicin in combination with cyclophosphamide in patients with breast cancer. Patients and Methods: Patients who had received prior anthracycline therapy were excluded. Cohorts of three patients with breast cancer were treated with escalating doses of pirarubicin (40 to 70 mg/m2) intravenously administered every three weeks in combination with cyclophosphamide (60 mg/m2) for 4 or more cycles.
Results: Eleven patients of stage I/II operable breast cancer received a total of 46 cycles of pirarubicin and cyclophosphamide as post-operative adjuvant chemotherapy. The most frequently reported treatment-related grade 2 adverse events were constipation (36%) and nausea (27%). There were no grade 3/4 events. Grade 2 leukocytopenia and grade 2 fatigue were dose-limiting at 70 mg/m2, the maximum-tolerated dose was 60 mg/m2. Grade 2 alopecia was reported in 60 and 70 mg/m2 pirarubicin group. Conclusion: At the MTD of 60 mg/m2 every 3 weeks, pirarubicin in combination with cyclophosphamide was associated with mild, reversible toxicity. The recommended phase II dose is pirarubicin 50 mg/m2 and cyclophosphamide 60 mg/m2 on day 1 every 21 days.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-13.
Abstract P5-10-14: Adjuvant Chemotherapy Treatment of Breast Cancer in Women 75 Years and Older
Authors: Kaplan HG , Malmgren JA , Atwood MK. 
Published: April 2011

Abstract
Background: Adjuvant chemotherapy is not generally recommended for women 75 years and over due to presence of comorbid conditions and lower stage.
Methods: We conducted a prospective cohort study of all women presenting with primary breast cancer (BC), aged 21-94, biopsy confirmed Stage 0-IV from 1990-2008 identified and tracked by our registry (n=8295). Clinical presentation characteristics including age, race, TNM stage, histologic type, surgical procedure, radiation and chemotherapy treatment were chart abstracted at diagnosis and follow up. Forward conditional stepwise regression was used to test for association significance for chemotherapy and the Kaplan-Meier method for disease free survival rate comparisons (DFS).
Results: Women aged 75+ represented 12% of patients in our community based cancer center registry database (n=962). No change in percentage of patients aged 75+ was seen over time. The majority of 75+ BC patients were stage 0-1 (63%) with 36% stage II-III (n=339). Initial patient treatment was 74% lumpectomy/radiation (n=708), 11% mastectomy/radiation, and 11 % mastectomy/no radiation. 82% were estrogen receptor positive and of these 76% were recommended treatment with hormone therapy. 70% of patients received an oncology consult and 8% (n=76) were recommended for chemotherapy. Of the 76 patients, 59 (78%) completed chemotherapy with incompletions due to complications of therapy (10), patient choice (4), unknown (1), other reason (1), and death (1). The most commonly given chemotherapy regimens were CMF (n=21), AC/Taxol (n=13), and AC (n=7) with 13 receiving an adriamycin containing regimen and 22 receiving non-standard therapy. In a conditional logistic regression model of TNM stage I-IV 75+ patients (n=847) with outcome=adjuvant chemotherapy, significant variables by order of entry into the model were 1) TNM stage, 2) Her2/neu status, 3) estrogen receptor status and 4) age at diagnosis. Chemotherapy treatment rates for 50-59 year olds were 51%, 60-64 = 40%, 65-69 = 28%, 70-74 = 19%, and 75+ = 8% (Pearson chi square = 687.78, p&lt;.001). DFS was equivalent for 75+ stage 0-I BC patients compared to 50-74 year olds, with a lower DFS rate among 75+ stage II-III patients (stage II: log rank test=10.21, p=.001, stage III: log rank test=4.14, p=.042).
Conclusions: TNM stage was the predominant factor in deciding to treat patients 75+ with adjuvant chemotherapy. Stage 0-I patients age 75+ and 50-74 had equivalent survival. Stage II-III age 75+ patients had significantly worse DFS than age 50-74 patients. There is an urgent need to identify effective and tolerable treatment regimens for stage II-II BC patients 75 years and older.
Figures available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-14.
Abstract P5-10-19: The Influence of Time to Completion of Chemotherapy on Survival in Patients with Triple Negative Stage III Breast Cancer
Authors: De Los Santos J , Hinton B , Carpenter J , LoBuglio A , Falkson C , Keene K , Meredith R , Krontiras H , Bland K , Wang C , Kim Y , Forero A. 
Published: April 2011

Abstract
Background: Neoadjuvant chemotherapy is increasingly delivered to facilitate breast conserving surgery through tumor downstaging. Prospective trials of neoadjuvant chemotherapy from the NSABP suggest no difference in survival outcomes in patients receiving neoadjuvant versus adjuvant therapy; however, subset analysis in 2 combined trials (B-18 and B-27) demonstrated a trend in DFS improvement in young patients (&lt;50 yrs), who often have more aggressive variant tumors. This study explores the possibility that patients with aggressive variant molecular subtypes [triple receptor negative (TN)] treated with modern chemotherapy, may significantly benefit from earlier completion of drug delivery. Methods: Billing codes for all breast cancer patients treated with chemotherapy between 1/1998 and 5/2005 at the University of Alabama at Birmingham were reviewed to comprehensively capture all Stage II and III patients with intact data. Patient, tumor, and treatment related variables were recorded and patients were divided to 4 molecular subtypes based on receptor status: hormone receptor (HR) positive, Her2 negative; HR+/− , Her2+; and triple receptor negative (TN). Kaplan Meier curves to assess survival were performed by dividing the TN group into 2 groups: those completing chemotherapy ≥5 vs &gt; 5 months from diagnosis. Results: 409 patients with Stage II-III disease with were identified: 124 received neoadjuvant and 285 received adjuvant chemotherapy. Out of this group, 81 patients had TN breast cancer (60 Stage II and 21 Stage III). Median age was 49 years. Median follow-up was 72 months. Chemotherapy consisted of adriamycin, taxol and cytoxan for a median of 9 cycles. Stage III patients who completed chemotherapy within 5 months had a statistically significant improvement in OS and DFS (p=0.03), and had a trend towards improvement in DMFS (p=0.10) when compared with those who took longer than 5 months to complete chemotherapy. Conclusion: Completion of chemotherapy in a shorter time interval in patients with Stage III, TN breast cancers was associated with an improvement in DFS and OS. Consideration of timing of chemotherapy warrants further study.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-19.
Abstract P5-10-23: Frequency and Cost of Chemotherapy-Related Serious Adverse Effects in a Canadian Population Sample of Women with Estrogen and/or Progesterone Receptor Positive Early Stage Breast Cancer
Authors: Hannouf MB , Brackstone M , Zaric G. 
Published: April 2011

Abstract
Background: Chemotherapy-related serious adverse effects (CSAE) reported by clinical trials of chemotherapy and by population-based assessments of CSAE in breast cancer populations with different clinicopathological characteristics may not reflect the experiences of women with estrogen and/or progesterone receptor positive (ER+/PR+) early stage breast cancer (ESBC). We aimed to characterize the risks and economic impact of CSAE among women in the Canadian general population treated with chemotherapy for ER+/PR+ ESBC. Methods: We used the Manitoba Cancer Registry to identify all women (n=665) diagnosed with ER+/PR+ ESBC during the period from January 1, 2000 to December 31, 2002. One-year of follow-up information from diagnosis, including hospitalizations and emergency room visits for all adverse effects that are typically related to chemotherapy, were identified by linking with Manitoba Administrative Databases including the Hospital Discharge Database and the Physician Claims Database. 251 women received chemotherapy during the 12 months after the initial diagnosis with ESBC. Hospitalizations or emergency room visits for CSAE and health care expenditures were compared between women who did and did not receive chemotherapy. We assessed the effect of chemotherapy on rate of CSAE using logistic regression, adjusting for menopausal status, lymph node status, anthracycline-containing chemotherapy agents, and comorbid indices. All statistical tests were two-sided.
Results: Women who received chemotherapy were more likely than those who did not to be hospitalized or visit an emergency room for CSAE (2.6% versus 9%, mean difference =6.4%, 95% CI=3.5% to 10%, p=0.01). In a logistic regression analysis, the rate of CSAE was found to be significantly greater for women with post-menopausal status (post-versus pre-menopausal, odds ratio 2.4; CI= 1.7 to 2.8) and 1-3 lymph node positive (LN+) (0 versus 1-3 LN+, odds ratio, 3.1; CI= 2.5 to 3.6). Chemotherapy recipients incurred large incremental expenditures for CSAE (pre-menopausal LN-: $1100 per person per year; post-menopausal LN-: $1600 per person per year; post-menopausal 1-3 LN+: $2200 per person per year).
Conclusions: The impact and costs of CSAE among ER+/PR+ ESBC are larger than predicted from clinical data and vary significantly by lymph node and menopausal status. Our findings, when combined with recent population-based data suggesting that women with ER+/PR+ ESBC may not gain benefit from chemotherapy as much as reported in clinical trials, have important implications for quality of life and could affect decisions regarding the use of chemotherapy in these patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-23.
Abstract P5-11-07: ER Positive Screen Detected Breast Cancers (SDBC) Do Not Require Chemotherapy
Authors: Bundred NJ , Morris J , Cheung S , Knox WF , Lawrence G. 
Published: April 2011

Abstract
Background: Meta-analysis of symptomatic breast cancer trials advises chemotherapy to women less than 70 years of age at high risk of death (i.e benefit of &gt;1% survival benefit from treatment) but UK screen detected breast cancers (SDBC) in women aged 50 to 65 years have a 97.2% relative survival compared to 77.6% for symptomatic cancers in the ABS at BASO audit.
Methods: To determine which women benefit from chemotherapy, we have analysed 1,607 symptomatic and SDBC in one unit. Results: SDBC had a significantly lower risk of relapse with the five year breast cancer mortality for ER positive breast cancers being low in the Excellent, Good and Moderate Prognostic Group 1 but being significantly higher in the Good Prognostic Group and Moderate Prognostic Group 1 diagnosed symptomatically. Symptomatic cancers in the Good Prognostic Group (GPG) and Moderate Prognostic Group 1 (MPG1) had a hazard ratio of 5.34 (1.61-17.75) and 14.46 (10.4-106.0) respectively for cancer death compared to SDBC.
NPI Index Score and Mortality in SDBC and Symptomatic Cancers treated in Manchester 1990-98 - ER
ER positive cancers detected by screening (but not ER negative) had a 0.6% mortality annually whereas the symptomatic cancers had a 10% annual mortality in the first five years. The UK National ABS/BASO Audit was used to confirm the findings (Table 2).
Data over the last ten years of follow-up from the ABS at BASO audit indicates significant survival improvements in the Moderate Prognostic Group 2 (MPG2) and the Poor Prognostic Group (PPG) for SDBC.
NHSBSP and ABS at BASO Breast Screening National Audit Data for Invasive SDBCs diagnosed between 1990 and 2002
Discussion: Thus, ER positive SDBCs represent a group which have a low risk of relapse and do not require chemotherapy. The improvements in survival of SDBC relate to better treatment of ER negative and HER2 positive breast cancers and have occurred predominantly in the MPG2 and PPG.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-07.
Abstract P5-11-14: Distribution of Tamoxifen and Five Metabolites into Normal and Malignant Human Breast Cancer Tissue during Conventional and Low Dose Treatment
Authors: Gjerde J , Gandini S , Guerrieri-Gonzaga A , Hauglid Flågeng M , Bonanni B , Macis D , Mellgren G , De Censi A , Lien EA. 
Published: April 2011

Abstract
Background: Biotransformation of tamoxifen leads to metabolites with different pharmacological and toxicological effects. Profiling and screening for active metabolites are important to assess their contribution to the overall therapeutic and adverse effects. The anticancer effect of tamoxifen is believed to be due to the hydroxylated metabolites 4hydroxytamoxifen (4OHtam) and 4hydroxyNdesmethyltamoxifen (4OHNDtam, endoxifen). Its demethylated metabolites have been related to side effects of the drug, whereas effects of tamoxifenNoxide (tamNoxide) have not been evaluated. In the present study we wanted to examine the distribution of tam and five of its metabolites in serum and normal and malignant breast tissues during normal dose (20 mg/day) and low dose (5 or 1 mg/day) regimens after 28 days of continuous dosing.
Methods: Serum and biopsies from 56 patients were available for analysis. The concentrations of tamoxifen and the metabolites 4OHtam, 4OHNDtam, Ndesmethyltamoxifen (NDtam), Ndesdimethyltamoxifen (NDDtam), and tamNoxide in serum and tissues were measured by means of a recently developed highly sensitive liquid chromatography tandem mass spectrometry (LCMSMS) method.
Results: Serum and biopsies from 56 patients were available for analysis. All compounds including the potent metabolites 4OHtam and 4OHNDtam were detected and measured in all samples. The tissue levels of tam and its hydroxylated and demethylated metabolites were highly related to the serum levels (p &lt; 0.000 — 0.0069). The tumor tissue to serum concentration ratios of tamNoxide decreased by increasing doses (p &lt; 0.0001) whereas this ratio was unchanged over the dose range 1-20 mg/day for the other compounds measured.
Conclusion: Tamoxifen and its metabolites were detected in all samples examined including those sampled during the low dose regimens. The tissue levels of tamoxifen and its hydroxylated and demethylated metabolites were strongly corresponding to the serum concentrations, in contrast to those of tamNoxide. The strong relations between the concentrations of the potent active 4OHtam and 4OHNDtam (endoxifen) in serum and target tissues suggest that implementation of therapeutic drug monitoring may represent a tool to improve tamoxifen therapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-11-14.