bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1-08-15: Pattern of Cardiac Monitoring and Risk of Trastuzumab Associated-Cardiac Dysfunction in a Clinical Practice: A Population Based Study.
Authors: Lee-Ying R , Ubhi C , Roberts S , Lim H , Bhatt H , Gesy K , Ahmed S 
Published: June 2012

Abstract
Background: Adjuvant trastuzumab therapy (ATT) in women with early-stage HER2+ breast cancer has been associated with significant reduction in the disease recurrence and mortality. Cardiac dysfunction (CD) is a known serious adverse effect of ATT. Although periodic cardiac monitoring is recommended during ATT, little is known about pattern of cardiac monitoring and incidence of CD in a clinical setting. The study aimed to determine extent of cardiac monitoring and rate of CD during ATT and to identify factors correlated with CD.
Methods: Medical records of women with localized HER+ breast cancer diagnosed between the years 2005–2007 in the province of Saskatchewan was reviewed. Women with advanced or recurrent disease or if they were treated in the setting of an adjuvant trastuzumab trial were excluded. A logistic regression analysis was performed to determine various clinical variables correlated with CD.
Results: A total 116 eligible women with median age of 54 yrs (range: 27–74) and median BMI of 27 (range: 44–17) were indentified. 40% had a cardiac risk factor & 30% were premenopausal. 51% had node positive & 53% had ER or PR+ breast cancer. 92% received anthracycline-based chemotherapy and 23% received sequential ATT. Of 62 patients with ER/PR+ breast cancer, 61% received adjuvant aromatase inhibitors. Baseline cardiac assessment was performed in 93% women. 98% women underwent periodic cardiac monitoring during ATT, 55% had monitoring performed at the interval of 3–4 months & 82% women had monitoring performed at the interval of 3–6 months. Mean baseline cardiac ejection fraction (EF%) prior to the commencement of chemotherapy and ATT were 65% & 63.9% respectively (p=NS). CD was observed in 32 (28%) women and only 4% were symptomatic. Trastuzumab was interrupted in 34%, and was discontinued in 20% women. Of 32 women with CD, 59% were referred to a cardiologist and 53% were treated with medication. CD was reversible in 84% cases. On multivariate analysis adjuvant aromatase inhibitor therapy was significantly correlated with cardiac dysfunction (Odd ratio 6.9 [95% CI: 1.4−33.0]). During the follow up period 18% women developed recurrent disease and 16% were died.
Conclusions: Our results confirm high compliance with cardiac monitoring, though not as frequently as recommended in the clinical trial setting. Overall the rate of symptomatic decline in cardiac function was similar to the rate reported in the clinical trials, however, a relatively higher incidence of asymptomatic decline in the left ventricle EF% was noted. Among various variables examined, adjuvant aromatase inhibitor therapy was associated with an increased risk of CD.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-08-15.
P1-10-04: Cost-Utility of the 21-Gene Breast Cancer Assay (Oncotype DX®) in the Irish Healthcare Setting.
Authors: Lacey L , Chien R , Hornberger J 
Published: June 2012

Abstract
Objective: The Oncotype DX® Breast Cancer Test is a validated 21-gene assay that predicts the likelihood of benefit from adjuvant chemotherapy in early-stage, node-negative and up to 3-node-positive, ER+ breast cancer as well as the likelihood of distant recurrence at 10-years. Study objective was to investigate the cost-utility (incremental cost per QALY gained) of using Oncotype DX® in early stage, node-negative, ER+ breast cancer patients, from the perspective of the Irish Healthcare system.
Methods: A cost-utility analysis was performed over the lifetime of the patient using a state transition model (Markov), which simulated the costs and quality-adjusted survival associated with and without the use of Oncotype DX® to inform adjuvant chemotherapy decisions. The model included 3 health states: no recurrence, recurrence and death. Transition probabilities between health states, utility scores associated with each of the health state, patient cohort characteristics and impact of Oncotype DX® on chemotherapy decisions data were derived from published sources. Direct medical costs associated with chemotherapy were collected from a representative panel of 5 hospitals in Ireland. Costs and outcomes were discounted at 4% per annum and the analysis was conducted over 30 years (lifetime horizon). Probabilistic and one-way sensitivity analyses were conducted. Results: Costs associated with adjuvant chemotherapy (4 cycles of TC) included the following costs: drug (€1,002); administration and monitoring (€1,646); adverse event prevention (€3,561) and adverse event management (€756). The average total cost of chemotherapy across hospitals therefore summed up to €6,965. The base case incremental cost per QALY gained with ODX testing was estimated to be €9,462. There was a 74% chance for ODX to be cost-effective at a willingness to pay threshold of €20,000. Conclusions: Using Oncotype DX® as a decision tool to inform adjuvant chemotherapy in node-negative, ER+ breast cancer patients, is likely to be cost-effective in the Irish healthcare setting. This estimate is probably conservative as the cost and disutility associated with long-term impact of chemotherapy related adverse events (i.e. such as cardiotoxicity, secondary leukaemia and potential cognitive impairment) have not been considered.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-10-04.
P1-11-06: Barriers to Enrollment in Cancer Therapeutic Clinical Trials: A Comprehensive Cancer Center Experience.
Authors: Bourdeanu L , Niland J , Stiller T , Swain-Cabriales S , Somlo G 
Published: June 2012

Abstract
PURPOSE: Well-conducted cancer therapeutic clinical trials are essential for improving patient outcomes. Unfortunately, less than 5% of new cancer patients participate in clinical trials on average nationwide. Failure to recruit eligible patients represents a major impediment to the success of clinical trials. Barriers to patient accrual in cancer clinical trials must be identified and overcome to increase patient participation.
MATERIALS AND METHODS: A retrospective analysis of 418 patients with a diagnosis of breast cancer seen at City of Hope Medical Center in 2009 was performed. Along with descriptive analysis of patient demographic data, logistic regression analyses were performed to evaluate predictors of enrollment.
RESULTS: Of the 418 new breast cancer patients in 2009, we determined that 138 (33%) were eligible for available therapeutic clinical trials at City of Hope. At the initial visits, physicians did not consider clinical trials in 32% (44/138) of these patients. Of the 138 eligible patients, 58% (80/138) of patients participated in clinical trials. The remainder (58/138, 42%) either declined trial participation despite meeting eligibility criteria (14/58, 24%), or were not considered for clinical trials by their respective physician (44/58, 76%). By logistic regression analysis, patients with Stages II and III disease were significantly more likely to enroll in clinical trials compared to those with stage 0 or I (OR=2.89, 95% CI, 1.17−7.12, P = .02; OR=9.17, 95% Cl, 2.65−31.76, P=0.0005;, respectively). Age, preferred language, marital status, family history of breast cancer, and race were not found to be significant predictors of enrollment in therapeutic clinical trials.
CONCLUSION: While enrollment of eligible breast cancer patients onto therapeutic clinical trials at City of Hope is high (58%), overall the proportion going onto clinical trials remains low (80/418, 19%), though higher than national averages. We found that the majority of patients did not enroll due to lack of availability of a suitable trial, ineligibility, or lack of offering of trial enrollment by the treating MD. Barriers to cancer clinical trial accrual should be prospectively identified and addressed in future studies, with the hope of leading to more vigorous enrollment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-06.
P1-11-08: Breast Cancer Screening Resources and Stage at Diagnosis in Appalachia: A Geospatial Perspective.
Authors: Yao N , Hillemeier MM , Anderson RT 
Published: June 2012

Abstract
Background: National Cancer Institute has designated Appalachia as a priority area characterized by significant disparities in cancer outcomes. However, little research focuses on the availability of cancer care resources in this region and how resource availability may relate to cancer outcomes. This paper will describe the distribution of breast cancer screening resources in Appalachia and examine the relationship between the screening resources and breast cancer stage at diagnosis at the population level.
Method: Percentages of early stage breast cancer incidence are computed based on the county-level data from the four Appalachian state cancer registry data from 2000 to 2008. Per capita breast cancer screening providers or facilities are computed for these Appalachian states. Descriptive analysis, exploratory spatial data analysis, and spatial regression were conducted.
Results: Appalachian counties had significantly fewer primary physicians, OB/GYN specialists, and diagnostic radiologists per capita than non-Appalachian counties. Spatial analysis demonstrates moderate clustering of scarce breast cancer screening resource and low percentage of early stage breast cancer incidence in West Virginia and Appalachian Kentucky. Those diagnosed at early stages were 67.92% of Appalachian vs. 68.34% of non-Appalachian breast cancer patients. The number of diagnostic radiologists per capita is significantly associated with the percentage of early stage breast cancer incidence when controlling for covariates such as county level poverty rates, uninsurance rate, percentage of adults with college degree, and per capita primary care resources.
Conclusions: Fewer diagnostic radiologists in West Virginia and Appalachia Kentucky are associated with lower percentage of early stage breast cancer incidence in the Central Appalachia region. Public health intervention could include policies and regulations to improve breast cancer screening resources in this region.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-08.
P1-11-09: Effects of a Multidisciplinary Breast Cancer Clinic in an Appalachian Based Medical Center.
Authors: Ingham JA , Cremeans DK , Daugherty SL , Myhand RC , Sever WE 
Published: June 2012

Abstract
Background: Adena Health System is a not for profit 250 bed institution that provides health care for a 13 county region in southeast, Appalachia Ohio. Access to health care in rural setting is an ongoing challenge. Several barriers to health care access affect this region. Socioeconomic burden and lack of higher education are two of the most dominant barriers. The age-adjusted beast cancer rates are 5.3% higher in the Appalachian region and the stage at presentation is more advanced. In December of 2009, we held our first Multidisciplinary Breast Cancer Clinic (MDBCC). The goal of the MDBCC is to facilitate prompt diagnosis and effective treatment. The MDBCC is staffed by a team of physicians consisting of surgeons, medical oncologists, and radiation oncologists. The team meets with the patient in a one on one setting. That same day the patients are discussed by the team with input from pathology and radiology in order to tailor a treatment plan specifically for each patient. After the conference, the recommendations are discussed with the patient before treatment is initiated.
Material and Methods: In a retrospective review, we evaluated the effect of a MDBCC on days to diagnosis, days from diagnosis to treatment, percentage of patients receiving neoadjuvant chemotherapy, and stage at diagnosis. Since December 2009, there have been over 90 breast cancer patients evaluated in the MDBCC. We randomly selected 60 breast cancer patients treated prior to MDBCC between 2008–09 and 66 patients evaluated at the MDBCC between December 2009–2011 from the tumor registry database.
Results: The average number of days to diagnosis pre-MDBCC was 15.5 days as compared to 4 days post-MDBCC. In 2008–09, the average days to treatment (pathology result to a-port placement, surgery or chemotherapy) was 18 days as compared to 12 days post-MDBCC. The percentage of patients receiving neoadjuvant chemotherapy has not changed significantly, however, there is an upward trend approaching statistical significance (10% per-MDBCC vs. 12% post-MDBCC). The stage at presentation has not changed significantly since the start of the MDBCC.
Discussion: The development of the MDBCC has proven to be a successful team oriented approach to breast cancer diagnosis and treatment. Time to diagnosis and initiation of treatment has improved. Providing patients with access to multiple specialists and forming a treatment plan the same day improves quality of care and lessens economic burden. The MDBCC is clearly feasible and particularly suited to the rural hospital setting. System wide, we hope to see a decrease in the stage at presentation and are confident based upon our current data that this in a realistic goal.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-09.
P1-11-13: Improvement in the Quality of Care for Patients with Locally Advanced Breast Cancer through Implementation of an Integrated Electronic Care Pathway.
Authors: Hogeveen S , Han D , George RL , Sweet-Goldstein M , Dinniwell RE , Muradali D , Brezden CB , Haq R , Simmons CE 
Published: June 2012

Abstract
Background: Locally advanced breast cancer (LABC) refers to the most advanced stage of non-metastatic tumours with an incidence of approximately 10% in newly diagnosed breast cancers. Currently, for optimal care, patients with LABC require a multidisciplinary approach including coordinated planning with medical, surgical and radiation oncologists. Many barriers may exist in co-ordinating timely management of these patients. Care pathways are important tools to streamline care and data collection and feedback allows for quality improvement in clinical practice. We created an interactive electronic care pathway and self populating quality assurance database at St. Michael's Hospital (SMH) to facilitate multidisciplinary teams to track LABC patient histories and patient treatments in order to coordinate therapy effectively and expedite care (LABC E-PATH).
Methods: This is an observational before-and-after cohort study of patients with LABC with a retrospective review pre-implementation and prospective collection of clinical data post-implementation. The completeness of workup and the timeliness of treatment pre- and post-implementation were assessed.
Results: With the implementation of the LABC E-PATH in May 2010, the time between the referral of an LABC patient to a medical oncologist and consultation has decreased from 7 days (range 0 to 493) pre-implementation to 2 days (range 0 to 29) post-implementation. The time between referral to medical oncologist and the start of their chemotherapy treatment decreased significantly from a median of 19 days to 8 days (pre-implementation: range = 0 to 493, postimplementation: range = 0 to 128) (p=0.0028). All pre-treatment staging was completed faster post-implementation of the LABC e-path than pre-implementation, expediting time to initiation of chemotherapy. The number of referrals for LABC to the SMH program increased from &lt; 1 patient per month to 4 patients per month post-implementation.
Conclusions: The LABC E-PATH has achieved its goal of expediting care and overcoming barriers to timely treatment in this patient population. It has also ensured timely and appropriate resource allocation. This unique system may also be applied to other disease sites where coordination of a multi-disciplinary team is critical for appropriate patient management.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-13.
P1-12-12: Evaluation of Ile655Val HER2 Polymorphism Associated with Cardiac Toxicity Following the Administration of Trastuzumab in Women with Non-Metastatic Breast Cancer.
Authors: Diorio C , Lemieux J , Côté M-A , Provencher L , Nadeau-Larochelle C , Jacob S , Demers É , Tremblay-Lemay R , Saint-Pierre C , Beauchemin M , Barabé F , Laflamme C 
Published: June 2012

Abstract
Background: Trastuzumab is well tolerated without major side effects except for cardiac toxicity. Although a number of clinical parameters have been associated with trastuzumab-associated cardiac toxicity (TACT), there is some indication that genetic variation of the HER2 gene may be associated with TACT in a population of metastatic breast cancer patients. However, this finding needs confirmation and we looked at a population of non-metastatic breast cancer.
Purpose: This study aimed to evaluate the association between cardiac toxicity and HER2 [Ile655Val] polymorphism in non-metastatic breast cancer patients treated with trastuzumab.
Method: The Ile655Val HER2 polymorphism was assessed in 41 women using TaqMan technology. For this study, the genotyping was performed using DNA extracted from normal breast tissue located at more than 1 cm of any other lesions. Charts review was used to collect information on TACT which was defined as a decrease in the left ventricular ejection fraction (LVEF) of ≥15% or ≥10% with a resulting LVEF &lt; 50% or any follow-up LVEF of &lt; 45%. The Fisher exact test was used to evaluate the association between cardiac toxicity and HER2 polymorphism.
Results: No deviation from the Hardy-Weinberg equilibrium has been observed for the allele and genotype frequencies. The distribution of HER2 polymorphism was 10 Ile/Val (24%) and 31 Ile/Ile (76%). In this population, 22% (9/41) developed a cardiac toxicity. The Val655Ile genotype was associated with cardiac toxicity (0.03). In this preliminary study, 50% (5/10) of Ile/Val carriers compared to 13% (4/31) of Ile/Ile carriers showed TACT.
Conclusion: HER2 Ile655Val polymorphism may be an efficient marker of TACT considering this tendency with this small cohort of patients. Larger sample is needed to strengthen this conclusion, since this result may influence on prescribing decision for adjuvant chemotherapy and anti-HER2 therapy in HER2 positive patients.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-12.
P1-12-13: Comparative Pharmacokinetics (PK) of Trastuzumab Emtansine (T-DM1) in Patients Who Have or Who Have Not Received Prior Treatment for Human Epidermal Growth Factor 2 (HER2)-Positive Metastatic Breast Cancer (MBC).
Authors: Wang B , Conte P , Casanova LA , da Fonseca Vinholes JJ , Saad OM , Yi J-H , Gupta M , Song C , Olsen SR , Perez EA , Girish S 
Published: June 2012

Abstract
Background: T-DM1, an antibody-drug conjugate composed of trastuzumab, a stable linker, and the cytotoxic agent DM1, is in development for the treatment of HER2−positive cancers. Single-agent T-DM1 3.6 mg/kg every 3 weeks (q3w) has demonstrated clinical activity in 2 phase II studies (TDM4258g and TDM4374g) in patients with pretreated HER2−positive MBC. The efficacy and safety of T-DM1 vs trastuzumab + docetaxel was investigated in patients with no prior MBC treatment in the randomized phase II study TDM4450g/BO21976. Here we report the PK of T-DM1 from that study and compare these data with those from studies that enrolled pretreated patients.
Methods: In all 3 studies, PK parameters, including maximum concentration (Cmax), area under the concentration-time curve (AUC), terminal half-life (t½), steady-state volume of distribution (Vss), and clearance (CL) were estimated by noncompartmental analysis (NCA) for serum T-DM1, serum total trastuzumab (conjugated and unconjugated), and plasma DM1. The effects of baseline trastuzumab and HER2 extracellular domain (ECD) concentration on T-DM1 exposure were explored and the relationship between T-DM1 exposure and clinical response (objective response rate [ORR] and progression-free survival [PFS]) was modeled.
Results: T-DM1 PK from evaluable patients enrolled in 3 studies are shown in Table 1. No significant correlations were observed between efficacy (as measured by ORR) and T-DM1 exposure (AUC, Cmax) after administration of T-DM1 to pretreated patients; efficacy-exposure analyses (ORR and PFS) for previously untreated patients will be presented. Patients with measurable concentrations of trastuzumab at baseline had a greater AUC during cycle 1; however, this did not impact ORR. Baseline circulating HER2 ECD concentrations also had no effect on ORR for pretreated patients. The impact of baseline trastuzumab and HER2 ECD concentrations on ORR and PFS in previously untreated patients will be presented.

Conclusions: Single-agent T-DM1 has similar PK in patients who have received prior therapy for MBC and in those who have not. The PK of T-DM1 was not affected by prior trastuzumab treatment or by circulating HER2 ECD, and no significant correlations were observed between efficacy (ORR) and T-DM1 exposure (AUC, Cmax) or HER2 ECD for pretreated patients. The relationships between efficacy and T-DM1 exposure and HER2 ECD concentrations will be presented for patients without prior MBC treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-12-13.