bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphatidyl-inositol-3-kinase Alpha catalytic subunit kinase domain mutations impart a favorable prognosis on estrogen receptor positive breast cancer through a mechanism that is independent of responsiveness to endocrine treatment.
Authors: Ellis MJ , Lin L , Crowder R , Tao Y , Evans DB , Steinseifer J , Bandaru R , Liu W , Gardner H , Semiglazov V , Baselga J 
Published: December 2010

Abstract
Abstract #6060
Background. Mutations in the alpha catalytic subunit of phosphoinositol-3-kinase (PIK3CA) occur in approximately 30% of ER positive breast cancers but the impact of PIK3CA mutation status on the response to endocrine therapy has not been adequately studied.&#x2028; Methods. cDNA and genomic DNA derived from baseline formalin-fixed core biopsy specimens from two neoadjuvant endocrine therapy trials (P024 and the letrozole alone arm of the RAD 2222 trial) were sequenced to detect exon 9 (helical domain - HC) and exon 20 (kinase domain - KD) mutations in PIK3CA. Interactions between mutation status and clinical, pathological and biomarker response to neoadjuvant letrozole and tamoxifen were determined.&#x2028; Results. No impact of PIK3CA KD mutation on the efficacy of letrozole or tamoxifen on either clinical, pathological or Ki67 biomarker response to neoadjuvant endocrine therapy was detected in either study. In the 2222 trial, PI3KCA mutation status (KD and HD) was associated with higher levels of pAKT (P=0.01) confirming these mutations activate the PI3 kinase pathway. Despite the lack of an interaction with short term endocrine therapy efficacy endpoints, PIK3CA KD mutation, but not HD mutation, was a favorable prognostic factor for relapse free survival in the P024 trial (RFS log rank P=0.02) and the protective effect was maintained in a Cox proportional hazards model for relapse that included post treatment (surgical), Ki67 and ER and pathological node status and tumor size (HR for no KD mutation, 14, CI:1.9-105 P=0.01). The KD mutation-associated protective effect was particularly dramatic in a tumor subset that exhibited a biomarker profile indicative of endocrine therapy resistance and poor outcome (RFS Log Rank P=0.007 within worst outcome group).&#x2028; Conclusion: In agreement with other studies, PIK3CA KD mutations but not HD mutations are associated with a favorable outcome in ER+ breast cancer but the protective effect of KD mutation is apparently independent of the degree of sensitivity to endocrine treatment. An alternative explanation for the protective effect of the presence of a KD domain mutation is that this mutation class reduces the metastatic potential of breast cancer. Pharmacological strategies that plan to specifically target tumors with PIK3CA KD mutations should take this possibility into account.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6060.
Predictive value of p27 for the benefit of adjuvant anthracycline-based chemotherapy in early breast cancer.
Authors: Conforti R , Moeder CB , Tomasic G , Boulet T , Nahta R , Yuan LX , Spielmann M , Delaloge S , Michiels S , Rimm DL , Esteva FJ , Andre F 
Published: December 2010

Abstract
Abstract #6063
Background: p27 is a cyclin-dependent kinase (cdk) inhibitor that plays a role in cell cycle regulation. The expression of this protein, assessed by immunohistochemistry (IHC), has prognostic value for overall survival in breast cancer patients (Porter P.L., J Natl Cancer Inst., 2007). Based on this, we hypothesized that p27 could be a predictive factor for the efficacy of adjuvant anthracycline (A)-based chemotherapy in early breast cancer.&#x2028; Methods: Tumor samples from 823 patients, included at Institut Gustave Roussy (IGR) in two randomized trials comparing an A-based chemotherapy with no adjuvant treatment, were used to construct a tissue microarray. We previously reported predictive values of ER, Her2 expression and molecular subclassification using the same tissue array (Conforti R., Ann Oncol., 2007). Nuclear and cytoplasmic expression of p27 was assessed by the AQUA system. A p27 ratio of nuclear and cytoplasmic expression (p27 N/C ratio) was calculated for each tumor sample. The prognostic and predictive value of the continuous value of p27 N/C ratio was assessed by a Cox regression model adjusted for treatment, age, tumor grade, stage and ER expression (IHC) and stratified by trial.&#x2028; Results: p27 was assessable in 715 primary tumors. The p27 N/C ratio was significantly different according to the molecular subclasses (p=0.001) and was higher in Her2- versus Her2+ and in EGFR+ versus EGFR- tumors (p=0.0075 and p&lt;0.0001 respectively). There was an almost significant interaction between p27 N/C ratio and disease-free survival in the adjusted Cox model (p=0.052). The adjusted hazard ratios (HR) of relapse or death of a unit increase in p27 N/C ratio was HR = 1.27 (95% CI = [0.58-2.81], p = 0.55) in the control arm and HR = 0.30 (95% CI = [0.12-0.77], p= 0.01) in the A-arm. For overall survival, the adjusted interaction p-value was equal to 0.08. The adjusted HR of death of a unit increase in p27 N/C ratio was HR=1.67 (95% CI = [0.61-1.73], p=0.32) in the control arm and HR=0.32 (95% CI = [0.10-0.99], p=0.05) in the A-arm.&#x2028; Conclusion: p27 N/C ratio, determined by the AQUA system, was borderline predictive for the efficacy of adjuvant A-based chemotherapy. However, this study is hampered by a relatively low number of events, a low dose of anthracycline, and multi-hypotheses testing (overall 20 biomarkers tested in different studies).
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6063.
Socio-economic deprivation independently predicts early recurrence in estrogen receptor positive breast cancer.
Authors: Mansell J , Monypenny IJ , Skene AI , Abram P , Carpenter R , Gattuso JM , Wilson CR , Angerson WJ , Doughty JC 
Published: December 2010

Abstract
Abstract #6081
Introduction: Socio-economic deprivation is associated with reduced survival in breast cancer, but little is known about how it affects the pattern of disease recurrence. We investigated the relationships between deprivation, other risk factors and recurrence in post-menopausal women with operable ER+ breast cancer.&#x2028; Methods: Patients who underwent potentially curative surgery for ER+ breast cancer between 1995 and 2005 at four UK centres were studied. Those patients whose area of residence was ranked in the highest quintile group according to the appropriate national Index of Multiple Deprivation were classed as deprived. The cumulative risk of recurrence was calculated using the Kaplan-Meier method, and hazard ratios were calculated using conventional and time-dependent Cox regression analysis stratified by centre.&#x2028; Results: 4110 patients were available for analysis, of whom 821 (20.0%) were classed as deprived. The median age at diagnosis was 62 years in both deprived and non-deprived groups. Tumour size and grade did not vary with deprivation status, but nodal involvement (38.0% vs 34.3%, p=0.05, Fisher's exact test) and lymphovascular invasion (28.1% vs 23.6%, p=0.01) were more prevalent in deprived patients. The latter were also more likely to undergo mastectomy (53.3% vs 47.2%, p=0.002) and less likely to receive adjuvant radiotherapy (50.4% vs 58.5%, P&lt;0.001) or chemotherapy (19.1% vs 22.8%, p=0.03).&#x2028; Median follow up was 5 years from diagnosis. Raw cumulative recurrence at 2.5 years was 8.4% (95% confidence interval 6.4-10.4) in deprived and 6.1% (5.3-6.9) in non-deprived patients. At 5 years the corresponding rates were 15.8% (13.1-18.5) and 13.3% (11.9-14.7). Only distant recurrence contributed to this difference, the local and contralateral recurrence rates being almost identical in deprived and non-deprived groups. Time-dependent Cox regression analysis showed that deprivation was a significantly stronger predictor of recurrence within 2.5 years of diagnosis than at later intervals, with or without adjustment for other prognostic variables (p&lt;0.05). For recurrence within 2.5 years, the unadjusted hazard ratio for deprivation was 1.64 (95% CI 1.22-2.22, p=0.001). After adjustment for age, mode of presentation, pathological variables and treatment, the hazard ratio was 1.51 (1.07-2.14, p=0.02).&#x2028; Conclusions: Post-menopausal women with ER+ breast cancer who are resident in areas of high deprivation are at increased risk of early recurrence, independently of known differences in tumour pathology and treatment.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6081.
Breast cancer mortality reduction in the western world: therapeutic versus diagnostic interventions. Implications for cancer care organization processes.
Authors: Ragaz J , Spinelli JJ , Semeniciw R , Hryniuk W , Budlovsky J , Franco E 
Published: December 2010

Abstract
Abstract #6083
INTRODUCTION. Recent epidemiology data show a substantial Breast Cancer (BrCa) mortality reduction in the western countries over the last decade. The literature indicates that both Adjuvant systemic treatments (Adj. SystTh) and Screening mammography (ScrM) contribute, but their interaction is not clear.&#x2028; Our study examines if contribution of Adj. SystTh separate from ScrM could be more clearly identified; and also, - as a second objective, - if organization of cancer care could be correlated with BrCa mortality outcomes.&#x2028; METHODOLOGY:&#x2028; The mortality trends were compared among three Provinces of Canada with different Levels of Provincial Diagnostic and Therapy Guidelines (PDTG):&#x2028; LEVEL I: most uniform coordination of PDTG: British Columbia (Brit.Col.), with a single Provincial budget; earliest implementation of Provincial Community Oncology Program (since the mid-1970's); and a uniform start of Adj. SystTh (late 1970's); and of ScrM (late -1980's).&#x2028; LEVEL II: medium (Ontario).&#x2028; LEVEL III: least uniform (Atlantic Provinces)*.&#x2028; BrCa annual age-standardized mortality rates per 100,000/population were obtained from Statistics Canada for the years 1950-2004, and expressed relative to the year 1950 (the baseline).&#x2028; RESUTLS: The 1950 BrCa mortality rates were: 30.9 for Canada; 31.4 for BC; 30.7 Ontario; 26.1 for Atlantic Provinces*.&#x2028; &#x2028; CONCLUSIONS:&#x2028; While both Adj. SystTh and ScrM contribute towards recent BrCa mortality reduction, the British Columbia data indicate that the impact of Adj. SystTh antedates that of ScrM, at least by a decade.&#x2028; Our data support a correlation of BrCa mortality trends with the organization of cancer care: Effective implementation of PDTG (- i.e. incorporating early curative interventions into guidelines), will have a strong impact on mortality trends, particularly if executed&#x2028; a. ongoingly,&#x2028; b. uniformly, and&#x2028; c. across the whole population.&#x2028; Our data therefore indicate that early implementation of curative systemic therapy - or of any curative intervention - is essential, as their delay may prevent materialization of survival gains.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6083.
Survival analisis in breast cancer's women in Santa Catarina, Brazil.
Authors: Schneider IJ , Orsi ED 
Published: December 2010

Abstract
Abstract #6093
BACKGROUND: Overall survival after breast cancer diagnosis is influenced by the characteristics study's group, the study's place and biological factors.&#x2028; OBJECTIVES: Define overall survival in five-years and the associated factors with the prognosis of breast cancer's women in Santa Catarina, Brazil.&#x2028; MATERIALS AND METHODS: this is a historic cohort study, with data from diagnoses from January 2000 to December 2002 from Registro Hospitalar de Cancer of the Centro de Pesquisas Oncológicas,SC and the Hospital de Caridade, both in south Brazil, and complemented with data from the Mortality Information System until December 2007. The time of survival was calculated as the range of the date of diagnosis (biopsy or surgery) until the date of death or end of monitoring (5 years). The survival curves were estimated by the Kaplan-Meier method, using the log-rank test for comparison of the curves stratified. The effect of co-variable model was estimated by the semi-parametric risk proportionate, Model Cox, with the Schoenfelder analysis of residuals to assess whether the co-variables of the final model respect the principle of proportionality over time. The analysis was made using R 2.5.0.&#x2028; RESULTS: 1002 women were included, and 262 deaths occurred, this 235 by breast cancer. The overall survival after 5 years was 76.2% (CI 95% 73,6-78,9%). Variables were associated with survival by the Kaplan-Meier curves: age, race/color, education, clinical stage, treatments received. This includes these variables in the model of Cox, remaining in the final model, as independent factors: age until 30 years (HR: 3,09, CI 95% 1,25-7,67); illiterate (HR 3,70, CI 95% 1,44-9,55); staging III (HR 5,27, CI 95% 2,56-10,82) and staging IV (HR 14,07, CI 95% 6,81-29,06); treatment with chemotherapy alone (HR 1,95, CI 95% 1,12-2,40), surgery, chemotherapy and radiotherapy (HR 2,38, CI 95% 1,36-4,16), compared to surgery and hormontherapy (HR 1.00). The Cox model variables respect the principle of proportionality over time (p=0,25).&#x2028; CONCLUSIONS: The overall survival in breast cancer, proved to be better than in other Brazilian states. The instruction presents itself as a strong influence on survival, where illiterate women have worse prognosis. The combinations of treatment are also factors independent and influenced by biological factors. The diagnosis in advanced stages is one of the most important factors for worse survival, and modifiable through campaigns of early detection and mammography screening.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6093.
Modifications in breast cancer presentation patern in Goiânia, Brazil: descriptive analyzes of a population based of 15 years in a developing country.
Authors: Freitas-Júnior R , Martins E , Freitas NM , Curado M , Oliveira J , Silva CB 
Published: December 2010

Abstract
Abstract #6095
Objective: To epidemiologically describe breast cancer among women living in Goiania, Brazil. Patients and Methods: cases were identified from the Population-Based Cancer Registry of Goiania for the period from 1989 to 2003. The variables studied were age, diagnostic method, topographic sublocation, morphology and breast cancer extent. Frequency analyses were carried out on the variables and means and medians for the age were determined. The SPSS® 15.0 software was used for statistical analyses. Results: 3,204 breast cancer cases were collected. The mean age was 56 years and the median was 53 years. Histological confirmation increased from 86.8% to 96.9%. Over the first five-year period, 91.3% of the cases did not present any specific location for the tumor, while 84.7% did not in the second and 59.1% in the third. Infiltrating ductal carcinoma (IDC) was the most frequent type, with 2,627 cases (82%). Regarding extent, 45.6% of the cases were found to be localized and 10.2% presented distant metastases. The in-situ case rate was 0.2% in 1989-1993 and increased to 6.2% in 1999-2003. On the other hand, the advanced case rate was seen to decrease from 24.1% to 6.3%. Discussion: The diagnostic profile of breast cancer in the city of Goiania is changing. Substantial increases in the numbers of early breast cancer are occurring, to the detriment of the numbers of advanced cases. This therefore suggests that the sporadic screening programs used up to the present time have in some way changed the face of breast cancer in our region.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6095.
Racial discripancies in breast cancer in urban hospital retrospective analysis.
Authors: Rana FN , Jasani N 
Published: December 2010

Abstract
Abstract #6098
Background: Certain races, specifically African-Americans, have less overall lifetime risk of developing breast cancer, but have higher mortality rates for the disease. Race has been found as an independent risk factor and may be associated with variables such as treatment differences, socio-economic factors and differences in biological behavior of tumor . The search for explanations for persistent disparity in outcomes of breast cancer between races particularly between African-American and Caucasian women stills seems to be elusive.The objective of this study was to help us better define if differences in outcomes for African-American women are due to specific tumor biology and/or socioeconomic issues. This will allow us to create programs with regards to screening, education and prevention directed toward high risk populations at our institution.&#x2028; Methods and Participants: Subjects included 446 women ( 189 blacks and 257 non blacks) aged 27 to 91 residing in metropolitan Jacksonville, Fl who were diagnosed with invasive or noninvasive breast cancer. Information on stage, insurance status, tumor profile/subtype, demographics and menopausal status was obtained from analysis of tumor registry at University of Florida/Shands Hospital between 2000 and 2005. Aggressive subtype was defined as triple negative (ER-, PR-, Her2 -) or HER2 + only. Indigent insurance was defined as Medicaid or no insurance. Advanced stage disease was defined as Stage IIb or greater. Menopausal status was defined as age greater than 50 as post menopausal and equal to or less than 50 as pre-menopausal. Comparisons were made by race with breast cancer subtype, insurance status, menopausal status and advanced stage presentation with differences analyzed by Chi-Square test.&#x2028; Results: There was a statistically significant difference in advanced stage disease between black and non-black patients (p= .0007). Advanced stage disease was present in 42% (95% confidence intervals [CI] 35% to 49%) of black females and in 28% (95% CI 22% to 33%) of non-blacks. There was a statistically significant difference in aggressive subtype between black and non-black females (p= .0012). Aggressive subtypes were present in 30% (95% CI 24% to 37%) of black females and 17% ( 95% CI 13% to 22%) in non-black females. Based on Cochrane Mantel-Haenszel analysis the odds of having an aggressive subtype are 1.81 (95% CI 1.13 to 2.89) times greater in pre-menopausal than post-menopausal females. An aggressive subtype was seen in 39% of black pre-menopausal females and in 27% of black post-menopausal females. There was no statistically significant difference in insurance status between black and non-black females.&#x2028; Conclusion: Black females tend to have more advanced breast cancer at initial presentation and aggressive tumor subtypes than non-black females. Aggressive tumor subtypes occurred at a higher prevalance in pre-menopausal black females compared.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6098.
Bevacizumab in combination with paclitaxel for HER-2 negative metastatic breast cancer: an economic evaluation.
Authors: Dedes KJ , Matter-Walstra K , Schwenkglenks M , Pestalozzi BC , Fink D , Szucs TT 
Published: December 2010

Abstract
Abstract #6104
Background: The addition of bevacizumab to weekly paclitaxel as primary chemotherapy for HER-2 negative metastatic breast cancer (MBC) prolongs progression-free survival without relevant increase of toxicity. However, the health economic implications of this costly treatment option have not yet been assessed.&#x2028; Material and Methods: We constructed a Markov model comprising three health-states: stable or responsive disease, disease progression and death. Markov cohort simulation was used to follow the clinical course of typical patients with MBC. Cycle length was one month. Information on response rates, major adverse effects was derived, and transition probabilities were estimated, based on the results of the E2100 clinical trial. Direct costs of treatment, major adverse events, laboratory tests, and disease progression were assessed from the perspective of a Swiss statutory health insurance perspective. Utilities for health states were obtained from the literature. Costs are reported in 2008 Euros (EUR).&#x2028; Results: Over the patients' lifetime, the addition of bevacizumab to weekly paclitaxel until disease progression is estimated to cost an additional 35'564 EUR and to yield a gain of 0.22 quality-adjusted life years (QALYs), resulting in an incremental cost-utility ratio of 164'921 EUR/QALY. In univariate and probabilistic sensitivity analyses, results showed a 95% CI from 117'998 to 484'251 EUR/QALY and were most sensitive to the cost of bevacizumab. Subgroup analysis indicated a more favourable cost-utility ratio (136'177 EUR/QALY, 95 % CI 97'999-435'823) in the age group &lt; 50 years.&#x2028; Discussion: Compared with commonly accepted willingness to pay thresholds in oncology, the addition 10 mg of bevacizumab per kilogram [body weight] to paclitaxel in MBC patients is expensive given the clinical benefit in terms of QALYs gained. Further research should consider patient age and alternative dosages for a more cost-effective utilisation of bevacizumab.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6104.
Adjuvant chemotherapy in breast cancer: is TC a cost-effective regimen compared to AC?.
Authors: Younis T , Rayson D , Skedgel C 
Published: December 2010

Abstract
Abstract #6110
Background: Adjuvant TC (taxotere 75 mg/m2 and cyclophosphamide 600 mg/m2 q 21 days X 4 cycles) has recently been shown to improve disease-free and overall survival compared to AC (adriamycin 60 mg/m2 and C 600 mg/m2 q 21 days X 4 cycles) for women with breast cancer. Given the possible differences in cost between the two regimens, an economic evaluation was undertaken to examine the cost-utility (CU) of TC relative to AC in terms of cost per quality-adjusted life year (QALY) gained. Methods: A Markov model was developed to calculate the cumulative costs and QALYs gained over a 10-year horizon for hypothetical cohorts of women with breast cancer treated with AC or TC. Event rates, costs, and utilities were derived from the literature. Costs expected with the delivery of standard courses of TC and AC at the Queen Elizabeth II Health Sciences Centre in Halifax, Canada were estimated. Costs included chemotherapy drug acquisition, supportive medications, laboratory investigations, health resource utilization, and significant adverse events associated with chemotherapy. Efficacy outcomes were based on the updated results of the clinical study of TC vs AC (Jones et al, SABCS 2007). The model took a third-party direct payer perspective and reports results in 2008 Canadian dollars ($). Both costs and benefits were discounted at 3%. Sensitivity analysis for key parameters in the model was conducted. Results: TC is associated with $4,080 incremental cost and 0.25 QALY gain compared to AC at 10-year horizon, with a favorable CU of $16,611/QALY gained. Results were robust to model assumptions and input parameters. Conclusions: TC is cost-effective compared to AC with a cost-effectiveness ratio well below commonly employed thresholds.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6110.