bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5-19-10: Correlation of Response of Weekly Paclitaxel and Paraplatin as First Line Treatment of Metastatic Breast Cancer with p53 Status.
Authors: El-Sadda W , Magdy M , Abdel-Halim I , Abdel-Wahab A 
Published: June 2012

Abstract
Background Paclitaxel is one of the most active drugs in metastatic breast cancer. Weekly paclitaxel seems less toxic & more efficient compared with paclitaxel every 3 weeks (possibly because of the proapoptotic and antiangiogenic activity), the dose intensity is quiet higher with tolerable toxicity. The sensitivity of tumors overexpressing p53 to paclitaxel is a matter of debate.
The purpose of study is to evaluate weekly paclitaxel and paraplatin in patients with metastatic breast cancer in terms of response rate, toxicity profile, relation of response to p53 status, progression free survival & overall survival.
Patients & Methods: Between September 2006 & September 2008, 60 patients with measurable metastatic breast cancer after adjuvant anthracycline treatment, WHO PS &lt;2, adequate renal, liver & bone marrow function. Patients received no prior chemotherapy for metastasis. Pathology specimens were evaluated for p53 status by immunohistochemistry (IHC). All patients received weekly paclitaxel 80 mg/m2 D1, D8, D15 (one hour IV infusion) and paraplatin AUC 5 D1 (IV infusion over half an hour) every 4 weeks for six cycles. Response was assessed every 2 cycles, patients showed an objective response (CR, PR or SD) had continued to 8 cycles.
Results: All patients were evaluable for response, toxicity & survival. Median age was 50 years range (42-64 years), median WHO PS 0. Main metastatic sites were lung 40%, liver 30%, LN 20%, Skin 12% & bone 50%. Forty percent of patients had one metastatic site, 40% had 2 metastatic sites and 20% had &gt; 2 metastatic sites.
The total number of cycles delivered was 466 with a median of 7 cycles / patient with no dose reduction. The overall response rate was 65% (CR 25%, PR 40%), SD 27% & PD 8%. Overexpression of p53 was found in 18 (30%) of the 60 studied patients, four of them showed only PR, compared to 30 patients having normal p53 status responded to treatment including 15 CRs. Overexpression of p53 had a significant negative impact on response to treatment (p=0.01). No grade 4 toxicity G2 anemia 15%, G3 neutropenia observed in 13.3%, G2 neuropathy occurred in 15%. Median time to progression & median survival were 18.5 & 28 months respectively.
Conclusion: The overall response rate achieved with weekly paclitaxel plus paraplatin is among the highest in metastatic breast cancer. However, the poor response rate seen in patients with p53 overexpression suggests the use of other combinations that may help to improve the outcome.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-10.
P5-20-02: N-Terminal Pro-Brain B-Type Natriuretic Peptide (nt-pro-BNP) before and during Treatment with Trastuzumab Allows Early Detection of Cardiotoxicity in Breast Cancer Patients.
Authors: Blancas I , Carrillo J , Legerén M , Delgado M , Jurado JM , Zarcos I , Villaescusa A , Gómez FJ , Moreno E , García-Puche JL 
Published: June 2012

Abstract
Background: The treatment with Trastuzumab (T) is associated with a certain degree of cardiotoxicity. This study sought to evaluate the level of nt-pro-BNP as a possible marker of cardiotoxicity so accurate as the value of left ventricular ejection fraction (LVEF)
Patients and methods: Forty patients with breast cancer treated with T were prospectively measured LVFE with echocardiography and nt-pro-BNP level before and every 3 months during T treatment. Median age: 50years(27;70). Received T as adjuvant treatment: 82.5% of the patients and 17.5% for metastatic disease.Patients with previous chemotherapy: 13(32.5%)neoadjuvant, 23(57.5%)adjuvant and 7(17.5%) for metastastic disease. Patients with previous treatment with anthracyclines: 12(30%)neoadjuvant, 21(52.5%)adjuvant and 2(5%)for metastatic disease(one patient had received anthracyclines too during adjuvant treatment).None received anthracyclines and T concomitant. Chi-square analyzed the correlation of high pathological level of nt-pro-BNP (values over the normal ***range, adjusted by the patient age) and a significative decrease of LVEF (more than 10% when LVEF &gt;50% or more than 5% when LVEF&lt; 50%)
Results: A decrease in LVEF was observed in 6 patients(15%) and pathological high levels of nt-pro-BNP in 7(17.5%).Two patients(5%) presented cardiac insufficiency with clinical symptoms, in both nt-pro-BNP was higher than 600pg/ml and LVEF lower than 40%. In the other patients the decreases of LVEF(never were&lt;40%) or high levels of nt-proBNP(never were&gt;600pg/ml)were not related to any clinical symptoms. Chi-square analysis showed a correlation between pathological high levels of nt-pro-BNP and significative decrease of LVEF (p=0.001), The estimated risk of a false negative nt-pro-BNP result (nt-pro-BNP normal value and significative LVEF decrease) was 2.735% (95 % confidence interval: 0.878 to 8.522 %) and the estimated risk of a false positive nt-pro-BNP result (nt-pro-BNP pathological value and no significative LVEF decrease) was 0.132%(95% confidence interval: 0.39 to 0.448%) Conclusion:The level of nt-pro-BNP is a possible marker of cardiotoxicity so accurate as the value of LVEF in patients with breast cancer treated with T.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-02.
P5-23-03: Breast Cancer in Elderly Treatment Algorithm – A New Approach To Optimize the Management of Breast Cancer in Older Patients.
Authors: Tahir M , Pretorius R , Robinson T , Walker R , Stotter A 
Published: June 2012

Abstract
Background: Elderly patients have been receiving a sub-standard treatment for early breast cancer when compared to younger age group patients. A higher percentage of them are being treated with primary endocrine therapy (PET) based on the premise that they may not survive surgery or live long enough to benefit from it. In clinical practice, however, there is no validated assessment in place to assess their surgical risk or estimate their life expectancy. This study aimed to optimize the treatment of early breast cancer in older patients using comprehensive geriatric assessment (CGA). It tested the hypothesis that CGA could be used to predict 2-year survival in older breast cancer patients. Based on that a treatment algorithm was devised which could be used to recommend whether PET or surgery plus endocrine treatment would be best indicated in individual patients. Methods: The study included women &gt;70 years of age with early breast cancer, seen in a dedicated Leicester clinic between 04/2005 and 04/2007. All patients had comprehensive assessment including documentation of co-morbidities, Mini-mental state examination (MMSe), Geriatric depression score (GDS), Activities of daily living (ADL), Instrumental activities of daily living (IADL) and American society of anesthesiologist score (ASA). Analysis was performed to find components of the CGA that were helpful in predicting 2-year survival in these patients.
Results: 123 patients were included; age range was 70–94 (median-82). Twenty-two patients died within 2-years. Logistic regression analysis found MMSe, ADL, and ASA score to have an independent association with 2-year survival. A statistically significant correlation (p-value 0.000) was found between the dichotomized combined-score of these components and 2-year survival. Breast Cancer in Elderly Treatment Algorithm (BCETA) was devised using the scores of these three components. Patients who scored one or higher (high-risk group), were found to have &lt;48% two-year survival; those, who scored zero (low-risk group), have &gt;86% chance of two-year survival. The overall accuracy for the algorithm was 81%.
Conclusion: Breast Cancer in Elderly Treatment Algorithm is a new and systematic approach to optimize the management of breast cancer in elderly patients. It is helpful in identifying high-risk patients with expected short-survival who may benefit from PET, if their cancer is hormone receptor positive. Patients with predicted longer life expectancy (low-risk) may be recommended standard treatment. A prospective study is ongoing at Leicester research clinic to validate the results.
BREAST CANCER IN ELDERLY TREATMENT ALGORITHM
Name:
Hospital No: DOB:
Address: Diagnosis:
COMPREHENSIVE GERIATRIC ASSESSMENT

TOTAL BCETA SCORE

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-23-03.
PD02-03: The Effect of Breast Conservation Therapy vs Mastectomy on Symptoms, Physical Impairments, and Function.
Authors: Kesarwala AH , Pfalzer LA , O'Meara WP , Stout NL 
Published: June 2012

Abstract
Background: Early-stage breast cancer (BC) patients choose between breast conservation therapy (BCT) and mastectomy based on comparable recurrence rates and overall survival. In the absence of mortality benefit, consideration of anticipated functional impairments could guide decision making. Although BCT offers less extensive surgery, the administration of radiation therapy (RT) may adversely impact upper extremity (UE) function. The purpose of this analysis is to investigate the effect of BCT vs modified radical mastectomy (MRM) without RT on functional impairments among BC survivors.
Materials and Methods: 196 women diagnosed with BC between 200105 were enrolled and treated in a prospective surveillance physical therapy program. 115 received either BCT, including lumpectomy and whole breast RT, or MRM without RT and were analyzed for this report. Participants’ UE range of motion (ROM), strength, and limb volume were assessed pre-operatively and at 1, 3, 6, 9, and 12+ months post-operatively by a physical therapist. Limb volume was assessed using infrared optoelectronic perometry. At 12+ months, overall health status, UE symptoms and function, and physical activity levels were reported using standardized questionnaires. Analysis of variance estimated differences in impairments and self-reported symptoms and function. One-way ANOVA analysis was used to determine significance between groups (p ≤ 0.05).
Results: 65 women (57.5%) received BCT and 50 women (42.5%) received MRM. No significant differences in age, BMI, stage, ER/PR status, and number of dissected lymph nodes were found between groups. At 1 month post-operatively, shoulder internal rotation (p=0.03), abduction (p=0.01), and flexion (p=0.004) were worse in post-MRM patients, with a trend towards worse external rotation (p=0.06). A higher rate of axillary cording was seen in patients post-MRM (p=0.02). By 12+ months post-operatively, there were no differences in any of the shoulder ROM variables. BCT patients reported, however, greater weakness (p=0.03) and diminished ability to perform heavy household tasks (p=0.03). There was no significant difference between BCT vs. MRM in rates of early lymphedema (40% vs 38%) or seroma (14% vs 22%).
Conclusion: Functional impairments represent an important category of morbidity for BC survivors and should be considered in pre-treatment decision making. Post-operative RT as part of BCT may not contribute significantly to impairment over the first year of treatment. The presence of self-reported weakness and difficulty performing heavy household tasks at 12+ months suggest possible future functional deficits, especially considering the potentially progressive nature of RT-associated tissue changes. Additional research is needed to assess longer-term changes and the impact of RT in the context of aggregate effects of other BC treatment modalities.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD02-03.
PD02-07: Models Predicting Non-Sentinel Node Involvement in Breast Cancer Also Predict for Regional Recurrence If the Axilla Is Not Treated.
Authors: Pepels M , Vestjens H , de Boer M , Bult P , van Dijck J , Mencke M , van Diest P , Borm G , Tjan V 
Published: June 2012

Abstract
Background
Series on breast cancer patients with sentinel node (SN) isolated tumor cells or micrometastases show low recurrence rates in the presence of SN isolated tumor cells, and varying recurrence rates in the presence of SN micrometastases. Non-SN prediction models are frequently used as a decision aid to identify patients that may not need axillary treatment, but this still needs to be validated in respect to regional recurrence.
Patients and Methods
We followed a cohort of 486 patients in the MIRROR-study of whom none received axillary treatment with favorable primary tumor characteristics and pN0(i+)(sn) or pN1(mi)(sn) for a median of 5 years. The patients were categorized into low or high-risk subgroups based on several published non-SN prediction models (cut-off levels between models varied from 3 to 10%), i.e. the Tenon Scoring system, MSKCC nomogram, Stanford nomogram and a Dutch model (Bolster et al.). The primary endpoint was 5-year regional recurrence-free survival.
Results
The overall 5-year regional recurrence rate was 3.0% (+/− 0.1%). Using the Tenon scoring system, we identified 438 patients with a low risk score of 3.5 or lower with a 5-year regional recurrence rate of 2.3% (+/− 0.8%), compared to a recurrence rate of 10.1% (+/− 0.4%) in 48 patients with a score above 3.5. For the MSKCC nomogram a low risk score of 0.10 or lower identified 300 patients with a 5-year recurrence rate of 2.8% (+/− 1.1%), and a score above 0.10 identified 166 patients with a recurrence rate of 3.4% (+/− 1.5%) (20 patients not assessable). By the Stanford nomogram a low risk cutoff level of 10% identified 21 patients without recurrence, whereas 465 patients had a 3.2% (+/−0.9%) recurrence rate. Using a Dutch model, a low risk cutoff score of 20 discriminated between 384 patients with a 5-year recurrence rate of 2.2% (+/− 0.8%) and 102 patients with a recurrence rate of 6.3% (+/− 2.9%). Further analyses with different cut-off values and subgroups will be presented at the conference.
Conclusion
Using several published non-SN prediction models for predicting regional recurrence, the Tenon scoring system outperformed the other models in that it identified the largest subgroup of patients with a low recurrence rate. We would recommend axillary treatment in patients classified as high risk according to the Tenon score.
Funding: Netherlands Organization for Health Research and Development (ZonMw 945-06-509).
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD02-07.
PD03-08: BRCA1-Like Triple Negative Tumors: Clinicopathological Variables and Chemosensitivity to Alkylating Agents.
Authors: Wesseling J , Lips EH , Oonk AMM , Smits RM , van Rijn CCM , Mulder L , Laddach N , Savola SS , Wessels LFA , Nederlof PM , Rodenhuis S , Imholz ALT 
Published: June 2012

Abstract
Background
Our group has previously employed array Comparative Genomic Hybridization (aCGH) to assess the genomic patterns of BRCA1-mutated breast cancers. It is reasonable to assume that this pattern indicates ‘BRCAness’ and thus serves as a marker for homologous recombination deficiency. This BRCA1-like aCGH profile is also present in about half of all triple negative sporadic breast cancers and has been shown to be predictive for benefit from intensive chemotherapy with DNA crosslinking agents. To study BRCA1-like tumors and conventional dose chemotherapy sensitivity in more detail, we compared clinical factors and survival rates in a uniform cohort of triple negative breast tumors treated with alkylating agents.
Patients and methods
103 patients with triple negative tumors received conventional dose adjuvant chemotherapy with doxorubicin/cyclophosphamide. DNA was extracted from tumor samples and BRCA1-like profiles were assessed. Tumors were classified as BRCA1 -like or non-BRCA1-like. Standard clinical and histopathological factors were determined and compared between both groups. Relapse free survival (RFS), disease specific survival (DSS) and overall survival (OS) after diagnosis were compared between BRCA1-like and non-BRCA1-like tumors.
Results
66 tumors (65%) had a BRCA1-like profile, while 35 tumors (35%) did not show such a profile. Patients with BRCA1-like tumors tended to be younger and had more often node-negative disease compared to the patients with non-BRCA1-like tumors (p=0.058 and p=0.034, respectively). There was no significant difference in survival between BRCA1-like and non BRCA1-like patients after treatment with alkylating agents: the median RFS was 121 vs. 109 months, median DSS was 129 vs. 114 months and OS was 127 vs. 110 months, for BRCA1-like versus non-BRCA1-like tumors. T-stage was the only variable significantly associated with survival.
Conclusion
BRCA1-like tumors occurred in younger patients and were more often node negative, which are features shared with tumors in BRCA1-mutation carriers. We did not observe a difference in survival between BRCA1-like and non-BRCA1-like triple negative breast cancers after treatment with conventional dose chemotherapy with alkylating agents. These results confirm our previous findings that BRCA1-like tumors have similar sensitivity to anthracycline-based adjuvant chemotherapy as other triple-negative tumors. It will be important to establish whether BRCA1-like tumors also share the exquisite sensitivity of BRCA-mutated tumors to PARP-inhibitors.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD03-08.
PD04-06: A Randomised Controlled Trial of Quality of Life and Fatigue after Support Group Intervention in Primary Breast Cancer Patients.
Authors: Granstam Björneklett H , Lindemalm C , Ojutkangas M-L , Berglund A , Letocha H , Strang P , Bergkvist L 
Published: June 2012

Abstract
Background: When diagnosed with breast cancer, most women's lives change as well as their perspectives on and appreciation of life. The aim of the present study was to evaluate whether psychosocial support intervention could influence health- related quality of life and fatigue during the first year after diagnosis.
Material and Methods: Of 382 patients with newly diagnosed breast cancer, 191 + 191 patients were randomized to an intervention group or to a routine control group respectively.
The intervention group received support intervention that lasted one week on a residential basis, followed by four days of follow-up two months later. The support intervention included informative-educational parts, relaxation training, mental visualisation and nonverbal communication. Health-related quality of life was measured using the EORTC-QLQ 30 and QLQ-BR23 questionnaires and fatigue with the Norwegian version of the Fatigue scale at baseline, 2, 6 and 12 months after intervention.
Result: There were a time-dependant improvement in both functional and symptom scales between baseline and 12 months as measured by the EORTC QLQ 30 and BR 23 questionnaires and there was a decrease in fatigue between baseline and after 2 months with further improvement up to 12 months in both groups but there were no differences between the intervention and control groups at any point in time.
Conclusion: Health related Quality of Life improves and symptoms of fatigue decreases over time, but we could not see any additional effect from the rehabilitation program in this setting.
Key words: Support intervention, breast cancer, health- related quality of life, fatigue, EORTC-QLQ 30 and BR 23, the Norwegian version of the fatigue scale.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-06.
PD08-11: Targeting Porcupine, a Critical Node for Wnt Signalling in Cancer.
Authors: Liu J , Pan S , Sun F , Kasibhatla S , Schuller A , Li A , Li C , Cui X , Wang T , Villarroel M , Mclaughlin M , Sellers W , Boral A , Harris J 
Published: June 2012

Abstract
Wnt ligands were first discovered based upon their transforming activity in the setting of mouse mammary tumor virus (MMTV) induced mammary carcinogenesis. Wnt signalling is required for normal development of the mammary gland and dysregulated Wnt signalling is implicated in cancers of the breast and colon among others. Furthermore, lobular breast cancer commonly shows reduced expression of E-cadherin that can lead to release of membrane-bound b-catenin into the cytoplasm and potentially increase Wnt signalling in the presence of Wnt ligand. To date, however, low-molecular weight therapeutic inhibitors of the Wnt pathway have not been developed. We set out to discover key points of intervention in the Wnt pathway and to develop low molecular weight inhibitors against such nodes. To this end, a cellular high-throughput screen for small molecule inhibitors of the Wnt pathway was performed. In this assay, cells secreting Wnt3a were co-cultured with cells harboring a luciferase reporter driven by the Wnt/beta-catenin responsive elements. Potent and specific Wnt pathway inhibitors were identified from this screen. To discern the mechanism of action of these compounds, a lead inhibitor was radiolabeled and used to probe protein targets in a radioligand binding assay. From these assays a candidate target of the inhibitor was identified as Porcupine. Porcupine is a membrane bound O-acyltransferase enzyme that is required for and dedicated to palmitoylating Wnt ligands, a necessary step in the process of Wnt ligand secretion. Inhibition of Porcupine blocks Wnt dependent activities, including LRP6 phosphorylation and the expression of Wnt target genes, such as Axin2, which in turn reduces the growth of cancer cells dependent on autocrine or paracrine Wnt signaling. A selective and orally bioavailable Porcupine inhibitor (NVP-LGK974) that inhibits the Wnt pathway in vitro and in vivo was developed through medicinal chemistry optimization. In preclinical evaluation, the compound robustly suppressed Wnt pathway signaling in vivo resulting in tumor regression in a murine breast cancer model driven by MMTV-Wnt1. In addition, this inhibitor attenuated tumor growth as a single agent and induced tumor regression in combination with Taxol in a human primary breast tumor model.
Wnt signalling is also important for the maintenance and homeostasis of normal tissues including gastrointestinal tissue. However, preclinical rodent efficacy models of cancer demonstrate that intermittent pharmacological inhibition of Porcupine can be effective against the tumor and mostly spare the normal gastrointestinal tissue, with an acceptable therapeutic window.
A Phase I dose escalation study of NVP-LGK974 in patients with melanoma and lobular breast cancer to evaluate the safety, tolerability, PK, and PD properties is expected to begin this year.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD08-11.