bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-03-06: Population Based In Vivo Biomarker Discovery Using Engineered Human Tumors
Authors: Wu M , Clark K , Deng N , Cai Z , Nicoletti R , Sun K , Feng B , Heyer J , Chiu I , Robinson M. 
Published: April 2011

Abstract
Background:
Tumors from patients exhibit significant inter-tumor variation, where each tumor harbors a unique set of genetic alterations that impact prognosis and response to treatment. Unfortunately, this variation contributes to low response rates in the clinic and creates significant challenges for treating patients with appropriate drugs. Cancer cell line based xenografts have traditionally been the preclinical model of choice to assess the efficacy of clinical compounds; however, such in vitro models exhibit inherent artifacts, and are unable to adequately capture natural variation seen in human tumor populations. It has therefore become a priority in oncology and personalized medicine to match patients to drugs that will result in a favorable treatment outcome. In this report, we describe a population based approach for response prediction featuring naturally occurring variation in tumors derived from genetically defined human-in-mouse models of cancer. Materials and Methods:
A population of De novo human breast tumors were generated by genetically engineering normal primary human breast epithelial cells with HER2 and SV40 early region (HER2/SV40er) or KRAS and SV40 early region (KRAS/SV40er) in an in vivo Human-In-Mouse (HIM) tissue transgenic model (Wu et al, Proc Natl Acad Sci U S A 2009, 106: 7022-2027). Each tumor of the population has been comprehensively characterized histopathologically, and at the RNA and DNA level. Furthermore, the population has been adapted to conduct quantitative efficacy studies of anti-cancer agents and combinations. Results:
The HER2/SV40er and the KRAS/SV40er HIM tumors develop as invasive human breast adenocarcinoma that are histologically similar to those observed in patients. Microarray and CGH profiling demonstrated significant inter-tumor variation among the established tumors, as has been reported for patient tumors. Moreover, the KRAS/SV40er tumors clustered with basal type breast cancers from patients, a poor prognosis human breast cancer subtype. Both HER2/SV40er and KRAS/SV40er tumors exhibited variable responses to treatments with the potent selective triple VEGFR inhibitor, tivozanib. Further characterization of those tumors, both pre-and post-treatment, identified potential biomarkers for tumor response to tivozanib. Discussion:
The genetically defined human-in-mouse tumors exhibited natural variations similar to that occurs in human cancer. This population-based HIM system enables us to identify and validate biomarkers of therapeutic response in an in vivo human tumor model. Figure available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-06.
Abstract P1-03-11: Combination of nab-Paclitaxel and Bevacizumab Inhibited Tumor Growth and Metastasis of a New Triple Negative Breast Cancer Model
Authors: Ran S , Trieu V , Volk LD , Wilber A , Desai N. 
Published: April 2011

Abstract
Background: Triple-negative breast cancers are highly aggressive and resistant to chemotherapy. In this study, we established a new model of triple-negative breast cancer and used it to test the novel combination of nab-paclitaxel with anti-VEGF antibody bevacizumab, which has been effective in treating other metastatic cancer types. Methods: The triple-negative HCC1806 beast cancer cells were stably transfected with dual reporters Red Fluorescent Protein (RFP) and Renilla luciferase to establish the new HCC1806-RR model. Immunodeficient mice bearing orthotopic HCC1806-RR tumors of 150mm3 in size were treated with saline (control), bevacizumab (4 mg/kg. i.p., twice a week, for 10 weeks), nab-paclitaxel (10 mg/kg, i.v., qdx5), or with combination of nab-paclitaxel and bevacizumab. Metastasis was analyzed by measuring luciferase activity in the lymph nodes (LN) and lungs. Results: The HCC1806-RR cells had identical morphology, proliferation rates and sensitivity to nab-paclitaxel as the parental HCC1806 cell line. HCC1806-RR tumors primarily metastasized to LN, with lung being a secondary metastatic site. Combination therapy of nab-paclitaxel and bevacizumab inhibited tumor growth by 100%, as compared to 0% for bevacizumab (P &lt; 0.001) and 90% for nab-paclitaxel (P = 0.024). Importantly, only combination therapy reduced incidence of LN and lung metastases by 50% (P = 0.007) and 87% (P = 0.001). Overall, 50% of the mice in the combination therapy group (n = 10) had complete regressions of both primary tumors and metastases at both regional and distant sites. Conclusions : The HCC1806-RR is a new triple-negative breast model with dual reporters to allow for quantitative assessment of metastatic spread. This model can be used to study the biology and treatment of triple-negative breast cancer. Combination of nab-paclitaxel with bevacizumab was highly effective against HCC 1806-RR tumors, suggesting that this regimen could provide clinical benefits to patients with triple-negative breast cancers.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-11.
Abstract P1-08-03: Alternative Dosing Regimens with Tarceva in a Mammary Cancer Model: Effects on Efficacy and Potential Effects on Toxicity
Authors: Lubet RA , Iwata K , Szabo E , Grubbs CJ. 
Published: April 2011

Abstract
The EGFR inhibitors (e.g., Tarceva) have been effective in preventing cancer in multiple animal models, including ER positive breast, head and neck, and urinary bladder cancers. Although Tarceva is less toxic than most classical cytotoxic therapies, the development of a skin rash in greater than 35% of patients is a significant impediment to its use in a preventive setting. We, therefore, tested whether alternative dosing regimens would still achieve preventive efficacy. Female Sprague-Dawley rats were administered a single IV dose of methylnitrosourea at 50 days of age. Beginning 5 days later, rats were administered Tarceva (6 mg/kg BW) by gavage. In the first study, three different protocols were employed: (1) dosing with Tarceva daily (7X/week), (2) dosing with Tarceva for one day followed by one day of vehicle treatment, and (3) two days of dosing with Tarceva followed by two days of dosing with vehicle treatment. These treatment regimens resulted in 94, 58, and 77% decreases, respectively, in cancer multiplicity when compared to rats receiving vehicle alone. In a second ongoing study, we are evaluating the following alternative dosing schedules. MNU treated rats are receiving either: (1) daily dosing with 6 mg/kg BW (total of 42 mg/week); (2) dosing 6 mg/kg BW, 2 days on-2 days off (total of 21 mg/week): (3) weekly dosing with a single dose of 42 mg; and (4) daily dosing with the vehicle. The various Tarceva treatment regimens have currently reduced palpable mammary tumor multiplicity by 82, 66, and 71%, respectively. These data imply that by significantly altering the dosing of Tarceva, including a dose of once per week, most of the preventive efficacy is retained. Pharmacokinetic studies from these protocols showed a t½ of &lt;8 hours; implying that sub-effective serum levels were achieved within 48 hours of the last dose. Whether these altered protocols may affect the induced skin rash in women is a significant and practical question. Supported by NCI contract number HHSN261200433001C.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-08-03.
Abstract P1-08-04: Doses of Selective Estrogen Receptor Modulations (SERMS) Required for Prevention and Therapy of Chemically-Induced Mammary Cancers
Authors: Heckman-Stoddard BM , Grubbs CJ , Johnson K , Lubet RA. 
Published: April 2011

Abstract
Selective Estrogen Receptor Modulators (SERMs) interfere with the activation of the estrogen receptor. SERMs have been shown to be effective for both treatment and prevention of breast cancer. Here we examine the ability of tamoxifen and arzoxifene, a more easily absorbed form of raloxifene, to prevent mammary tumors at a significantly lower dosage than those used for treatment. For prevention studies, female Sprague-Dawley rats (50 days of age) were injected with a single i.v. dose of MNU resulting in the development of multiple ER-positive mammary tumors beginning 7 weeks after carcinogen treatment. Rats were administered the preventive agent beginning five days after carcinogen administration. When the agents were tested at does varying between 0.15-3.3 ppm in the diet, both agents caused a dose dependent increase in preventive activity. The highest doses of tamoxifen (3.3 ppm) and arzoxifene (3.0 ppm) both decreased tumor multiplicity greater than 90%. Both of these doses are less than one-fifth the human equivalent dose (HED) based on standard FDA scaling factors. Both doses also resulted in substantial decreases in mammary gland development. These dosages were then used in a therapy setting to compare the efficacy. For these studies, MNU treated rats were allowed to develop their first palpable mammary tumor (70-150 mm2) before initiating treatment. Tumor growth or regression was followed by caliper measurements. Neither of the preventive doses of these SERMs exhibited therapeutic activity although substantially higher doses of tamoxifen (33 or 100 ppm) were relatively effective. These results are in contrast to our prior findings with other classes of agents (RXR agonists, EGFR inhibitors, and aromatase inhibitors) in which highly effective preventive doses were as effective as therapeutic doses in this model. These results demonstrate the unique dose differential regarding prevention and therapy with SERMs. Microarray analysis of tumors treated for 5 days with tamoxifen at doses of 3.3ppm or 100ppm reveals overlapping significant gene changes of similar magnitude in comparison to control treated tumors although there were significant gene changes seen at the therapeutic dose which were not observed at the lower dose. These studies raise two questions: 1) whether this class of agents might be used at significantly lower doses in a pure prevention setting as contrasted with a therapeutic setting where they were initially defined; 2) are there gene expression changes which might be used to help identify this differential dosing for prevention vs. therapy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-08-04.
Abstract P1-09-05: Re-Testing of HER2 Status in Recurring Metastatic Breast Cancer Is a Clinically Relevant and Cost-Effective Strategy
Authors: Bernow M , Wilking U , Bergh J , Jönsson B , Wilking N. 
Published: April 2011

Abstract
Introduction
Previously HER2 status has been shown to change in 6 to 30% of recurring metastatic breast cancer (RMBC) patients (pts). Still most clinicians base trastuzumab (TZ) re-treatment decisions on prior HER2 testing of the primary tumor. This study investigates cost-effectiveness of re-testing of HER2 status (REHER) of metastasis in RMBC pts before TZ treatment in a Swedish setting. Materials and methods
A Markov state transition model is used to simulate six different strategies for REHER and treatment of RMBC. The analysis is performed for two cohorts with different patient management and resource use, based on:
I Treatment guidelines and published data on the patient group (guideline cohort, GC);
II Clinical practice with real life data from a Swedish breast cancer database (real life cohort, RLC).
Quality adjusted life year (QALY) weights and risks of progression and breast cancer death are taken from literature. Outcomes are measured as QALYs gained and costs, including both direct and indirect costs. Analyses are performed with life time perspective and both costs and outcomes are discounted at 3%. Costs have been converted to USD with an exchange rate of 7.367 SEK/USD.
Testing and treatment strategies.
Results
Chemotherapy alone for all pts (strategy 0) is least costly and results in 1.309 QALYs gained. IHC testing all pts and treat FISH confirmed IHC 2+ 3+ pts with TZ (strategy 4) has lowest incremental cost-effectiveness ratio (ICER), $63,200 and $61,100 for GC and RLC respectively. FISH testing all pts and treating FISH+ with TZ (strategy 5) is the most efficient strategy resulting in 1.543 QALYs gained with an ICER at $75,500 and $73,300 respectively. Strategies 1 and 3 are dominated by simple dominance (less expensive alternative with better outcome). Strategy 2 is dominated by extended dominance (alternative with better effectiveness and lower ICER).
Results for guideline and real life cohorts.
Conclusion
The cost of patient management calculated based on guidelines is similar to the one based on observed clinical practice. RLC is less costly but both cohorts give the same ranking of strategies. A Swedish study estimated willingness to pay (wtp) in Sweden to 88,900 $/QALY gained. If TZ treatment is an option REHER of metastasis is clinically relevant and cost-effective. Depending on the wtp strategies 4 and 5 can be considered. Interesting to notice is that strategy 1 (no re-testing of metastasis), probably the most common one used, is dominated and thus suboptimal regardless of wtp per QALY.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-09-05.
Abstract P1-09-08: Survival, Health Care Cost and Utilization of Patients with Triple Negative Breast Cancer in a U.S. Managed Care Setting
Authors: Baser O , Wei W , Henk HJ , Xie L , Teitelbaum A. 
Published: April 2011

Abstract
Objectives: Triple negative breast cancer (TNBC), a subtype of breast cancer characterized by its unique molecular profile and aggressive clinical behavior, lacks satisfactory standard therapies. Little is known about survival and economic cost of patients with TNBC. This study was conducted to compare the survival, health care cost and utilization of patients with TNBC versus patients with breast cancer that is not triple negative.
Methods: Analyses were conducted using Impact Intelligence Oncology Management (IIOM) (2002-2009) linked with United Health administrative claims. Patients were followed from the time of initial breast cancer diagnosis until death, disenrollment or end of the observation period. Continuous enrollment was required during the observation period. Staging and estrogen and progesterone receptors (ER/PR) and HER2 status were obtained at time of initial diagnosis. Patients’ age, region, cancer stage, comorbid conditions, health care costs and utilization prior to the initial diagnosis were controlled for risk-adjusted comparison. Cox regression was used for survival analysis. Health care resource use during the follow-up after initial diagnosis, such as number of hospitalizations, emergency room (ER) visits, office visits, outpatient visits and oncologist visits, were modeled with negative binomial regression. Since variable length of follow-up is allowed in the study design, we used inverse probability weight adjusted generalized linear models to estimate risk-adjusted annual total health care costs. Using a similar approach, we compared adjusted inpatient, pharmacy, office, outpatient, emergency and other costs between both groups.
Results: The study included 450 patients with TNBC and 1,807 patients without TNBC. At time of diagnosis, TNBC patients were younger (54 vs. 57, P&lt;0.001) than patients with no TNBC. After controlling with baseline differences, overall mortality risk rate for TNBC patients were over two times higher (HR: 2.15, P&lt;0.002). Stratified Kaplan-Meier (KM) analysis showed that the best survival rates were for stage I-III non-TNBC patients, followed by stage IV non-TNBC patients and stage I-III TNBC patients. The highest death rates occurred for stage IV TNBC patients. Adjusted comparison showed that patients with TNBC had significantly more annual number of hospitalizations, hospitalization days and number of ER visits relative to non-TNBC patients (1.28 vs. 0.95 P&lt;0.001, 10.20 vs. 6.07 P&lt;0.001, 1.30 vs. 0.93, P&lt;0.003). Although similar in annual total health cost, total adjusted inpatient costs for TNBC patients were almost 50% higher ($9,581 vs. $6,506, P&lt;0.001).
Conclusions: The economic and clinical burden of patients with TNBC is significant versus patients with breast cancer that are not triple negative.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-09-08.
Abstract P1-10-06: Racial Disparities in Physical and Functional Domains in Women with Early Breast Cancer
Authors: Morehead Gee A , Pfalzer L , Stout N , Levy E , McGarvey C , Springer B , Soballe P , Gerber L. 
Published: April 2011

Abstract
Background. There is limited research on the racial/ethnic disparities in breast cancer survivors’ (BCS) physical functioning and quality of life (QOL). Previous studies note that African American (AA) women are typically diagnosed with larger, more aggressive tumors and require more intensitve surgical and adjuvant treatment potentiating higher levels of functional morbidity. Reasons given for these disparities include; genetic predisposition, poor access to screening and cultural norms that may impact a patients willingness to seek screening and early treatment. This analysis compared the QOL and prevalence of physical impairments (including lymphedema, seroma, cording) of white and African-American BCS from a US Military hospital where all patients have coverage and access to health care services. Methods. Data was analyzed from 166 women (130 white and 28 African-American). Participants were assessed preoperatively and examined at 1, 3, 6, 9, 12-24 months post surgery for impairments by a physical therapist. QOL was assessed at 12-24 months post-operation through the Short Form Health Survey (SF36v2). Analysis of variance estimated differences in QOL and occurrences of impairments between white and African-American BCS. Results. African-American BCS: were premenopausal(P&lt;.05), had ER/PR negative tumors(P&lt;.001, P&lt;.05), and received radiation(P&lt;.05). No significant differences were found in type, stage, grade, or size of BC tumor, surgery type, lymph node dissection, or number of lymph nodes sampled. More AA BCS were employed(P&lt;.05) and socially active(P&lt;.05), but less recreationally active(P&lt;.05); there were no significant differences in marital status. More AA BCS had axillary web syndrome(P &lt;.05) and lymphedema(P &lt;.05). No significant differences were found in seroma, fatigue, chestwall pain, shoulder pain, numbness, and self-reported QOL. Conclusions. Results suggest a difference in physical effects of BC treatment on white and AA women; however, contrary to other studies, no differences in QOL were noted. Our cohort demonstrates an interesting trend, in that only ER/PR status differed and other characteristics of the tumor were not different between racial groups. This differs from past reports and may suggest that access to care plays a role in promoting earlier stage diagnosis. However, despite the homogeneity of our cohorts tumor status we found that AA BCS may be at a higher risk for common impairments associated with BC treatment and should be monitored prospectively to mitigate the potential for impairments. Further research should examine effects of BC treatments on women of various ethnicities.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-10-06.
Abstract P1-10-08: Breast Reconstruction Surgery Following Mastectomy: Love or Money?
Authors: Al-Allak A , Knight H , Walter C , Court F , Chan HY. 
Published: April 2011

Abstract
Introduction
All women should be considered for breast reconstruction following mastectomy, providing they are medically fit. The proportion of women having a reconstruction varies significantly from centre to centre; a key reason for this is the availability of reconstruction in that centre. In countries with an insurance funded health care system, breast reconstruction may also be influenced by the ability to pay. In the UK, breast reconstruction is available for free on the National Health Service (NHS). The aim of our study was to identify any other factors that may influence a woman's decision to have a reconstruction. Methods
All women having a mastectomy under the care of one breast surgeon between 2000 and 2010 were included. Data were collected retrospectively and included: age at surgery, marital status, dependents under 18, employment status, home circumstances and Zip code. The Index of Multiple deprivation (IMD2007) was derived for each patient from their zip code using the UK National Statistics data. The patients were divided into two main groups: those who underwent reconstruction and those who opted for mastectomy only. The Mann-Whitney U test was used to determine whether there was a statistical difference between the two patient groups using the statistical package R.
Results
A total of 272 patients underwent mastectomy during the study period, of these patients 148 had mastectomy only (median age 67, range 34 — 95) and 124 had a reconstruction (median age 51, range 28-73). When the two groups were compared statistical analysis revealed that the reconstruction group were younger (P&lt;0.002), more likely to be married or have a partner (p=0.00065), have dependents (P&lt;0.0005) and work (P&lt;0.0005). There was no significant difference between the two groups socioeconomic status.
Conclusion
These data suggest that social and economical inequalities do not affect the decision making process for breast cancer patients in a society where health care is free at the point of delivery. However young age and a stable family/partner do.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-10-08.