bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic Signature of TNBC Patients with Good Prognosis.
Authors: Kim K. , Lee E. , Lee J. , Bae J. , Korea Breast Cancer Society . 
Published: December 2010

Abstract
Objectives We analyzed the molecular breast cancer subtypes using Korean Breast Cancer Society Registration Program data during 1993-2006 to compare the clinical feature and prognosis for "triple-negative" breast cancer with other types of breast cancer.We also compared patients expired from breast cancer within 3 years of diagnosis with the others in triple-negative breast cancer patients to find clinicopathologic variables influencing prognosis.Patients and methods We studied a cohort of 38,356 breast cancer patients, with assessable data for ER, PR, and Her-2/neu status. Patients were divided in four groups: luminal A (ER+ and/or PR+, HER2-), luminal B (ER+ and/or PR+ HER2+), triple-negative (ER-, PR-, HER2-), and Her-2/neu (ER-,PR-, HER2+). The median follow-up time was 75.6 months. Age, nodal status, tumor size, histological grade, p53 mutation status, and breast cancer-specific survival were evaluated.Results The luminal A(15,605patints, 40.7%) subtype was the largest in our study sample compared with luminal B(3,646patients, 9.5%), triple-negative(6,438 patients,16.8%), and Her-2/neu(4,035patients, 10.5%) subtype.Compared with breast cancer-specific survival of the luminal A subtype and luminal B, the triple-negative(OR=2.38) subtype and Her-2/neu(OR=2.65) subtype had shorter overall survival. Triple-negative subtype was correlated with more advanced stage(P &lt; 0.0001), higher histological grade(P &lt; 0.0001), and more frequent p53 overexpression(P &lt; 0.0001).Those with triple-negative breast cancer had an increased likelihood of mortality within 5 years of diagnosis(P &lt; 0.0001). But, thereafter, the risk of death declined rapidly. In luminal A and luminal B group, the risk of death was constant over 7 years of follow-up. Overall, the triple-negative group had a “good” long-term prognosis.There were annual improvement in 3 year survival rates for other hormone-positive breast cancer patients from 1998 to 2004(mean rate=0.67%/year). But, triple-negative breast cancer group had no survival improvement in the same period.2831 triple-negative breast cancer patients had assessable follow up data over 3 years. 283 patients(10.0%) expired from breast cancer within 3 years of diagnosis. Tumor size, nodal status, histological grade were correlated with breast cancer specific mortality, in univariate analysis with triple-negative breast cancer patients. Histological grade was the only factor to have correlation with breast cancer specific mortality in multivariate analysis.Conclusion Triple-negative breast cancer has more aggressive clinical course than other forms of breast cancer. It is necessary to develop new prognostic marker and effective therapeutic strategy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4065.
Predicting Survival Time in Women Starting First Line Chemotherapy for Advanced Breast Cancer.
Authors: Lee C. , Stockler M. , Malcolm H. , Coates A. , Val G. , Sally L. , Richard S. 
Published: December 2010

Abstract
Purpose: Women starting first line chemotherapy for advanced breast cancer have widely differing baseline characteristics and ultimate survival times. We sought to develop and validate a pragmatic prognostic index for clinical practice and research based on simple clinical and laboratory data.Methods: Prognostic models were developed in 378 women treated with CMF in the control groups of 3 randomized trials, and validated in 564 women treated with AC or mitoxantrone or capecitabine in the experimental groups of these trials. Multivariable censored linear regression of log-transformed survival times was used to select prognostic variables, which were then dichotomised to define negative prognostic features (NPFs). The effects of NPFs on survival time are expressed with hazard ratios (HR) and p-values from multivariable Cox models.Results: There were 7 independently significant NPFs (see table). In the development dataset, an elevated neutrophil count or history of brain metastasis approximately halved survival time, while the other NPFs reduced survival time by about one third. Women with 0 NPFs (15%) had a median survival of 18 months, about 1.4 times as long as those with 1 or 2 NPFs (63%, 13 months), and about 2.6 times as long as those with 3 or more NPFs (22%, 7 months). In the validation dataset, the effects of brain metastasis and elevated neutrophils were more modest, and most NPFs reduced survival by about one third. The median survivals of women with 0 NPFs (17%), 1 or 2 NPFs (60%) and 3 or more NPFs (23%) were 21 months, 13 months and 8 months respectively.Conclusions: A prognostic index using widely available baseline characteristics could improve prognostication in clinical practice. Stratification of patients using the prognostic index could improve the efficiency of randomised trials. Development (n=378) Validation (n=564) Negative prognostic feature% of womenHRp-value% of womenHRp-valueBrain metastasis32.410.00641.730.002Neutrophil count &gt;ULN121.910.001151.350.03ALP &gt;2 x ULN221.660.001201.380.008Age &gt;60451.490.001451.210.05Hb &lt;120g/L351.480.03291.230.05ER negative401.360.02281.52&lt;0.001ECOG 2 or 3271.320.03251.500.001ULN = upper limit of normal Development (n=378) Validation (n=564) Number of NPFs% of womenHRp-value% of womenHRp-value 150.850.30170.670.0021 or 2631.00-601.00-3 or more222.11&lt;0.001231.97&lt;0.001NPF = negative prognostic feature
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4066.
Immunoglobulin Kappa C Has Independent Prognostic Significance in Node-Negative Breast Cancer.
Authors: Schmidt M. , Boehm D. , Lebrecht A. , Gehrman M. , Koelbl H. , Hengstler J. 
Published: December 2010

Abstract
Background: Utilizing microarray based gene-expression analysis of fresh-frozen tissue we could recently demonstrate the prognostic impact of a B cell metagene in node-negative breast cancer (Cancer Res 68: 5405-5413, 2008). In the present study we investigated the prognostic significance of immunoglobulin kappa c (IGKC) in formalin-fixed paraffin embedded (FFPE) breast cancer specimens of 363 node-negative breast cancer patients which were not treated in the adjuvant setting.Methods: RT-PCR was used to analyze mRNA expression of IGKC in FFPE tissue of 363 patients with node-negative breast cancer. Additionally to IGKC we examined the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER) and progesterone receptor (PR). Metastasis-free survival (MFS) was analyzed with uni- and multivariate Cox regression.Results: Median follow-up was 10 years. 69 patients (19%) developed distant metastasis. Univariate analysis showed significant results for histological grade (HR 2.2, 95% CI 1.54-3.19, p&lt;0.0001), tumor size (HR 1.48, 95% CI 1.22-1.77, p=0.0002) and IGKC. Patients with a higher expression of IGKC showed better MFS (HR 0.84, 95% CI 0.76-0.92, p= 0.0004). Age, ER and PR failed to show an association with MFS in univariate Cox regression. Using multivariate Cox regression, IGKC retained its independent prognostic significance (HR 0.85, 95% CI 0.77-0.93, p=0.0005). Besides IGKC histological grade (HR 2.5, 95% CI 1.62-3.77, p&lt;0.0001) and ER (HR 1.08, 95% CI 1.01-1.16, p=0.031) showed an independent association with MFS.Conclusion: Utilizing FFPE we could prove the independent prognostic significance of IGKC in 363 node-negative breast cancer patients. This should aid in incorporating the prognostic impact of the immune system into prognostic algorithms based on FFPE tissue.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4067.
A Quantitative Immunofluorescence Assay (AQUA) Suggests Significant Misclassification (15%) of Estrogen Receptor Status in Breast Cancer.
Authors: Welsh A. , Moeder C. , Alarid E. , Rimm D. 
Published: December 2010

Abstract
Introduction: Estrogen Receptor (ER) is arguably the most powerful predictive marker in breast cancer. However, a recent incident in Canada revealed a strikingly high false-negative rate and raised awareness of the current limitations in our measurement of ER. The current clinical standard is both subjective and qualitative. Even though guidelines are about to be issued to standardize this assay, there is very little data on the misclassification rate in current practice in the US.Hypothesis: Our hypothesis is that the use of a quantitative assay for ER on a series of retrospective collections may reveal both the level and significance of the misclassification rate.Method: Cell lines with a range of ER expression levels were analyzed by quantitative western blotting in parallel with IF/AQUA analysis (r2 = 0.865), in order to create standard curves for assessment of absolute ER protein concentration in tissue. The optimized assay was then used to quantify ER protein expression in a large cohort of archival breast cancer samples from Yale (1962-1982, n =617).Results: Using a set of standard curves with recombinant ER and cell line controls, we developed a standardized method for quantifying ER as an absolute concentration (pg ER per μg total protein) in formalin-fixed tissue on TMAs. This ER AQUA assay has a range in sensitivity from 50 pg/μg to 1500pg/μg total protein. Quantification of ER protein expression on the Yale archival cohort revealed a unimodal distribution with 49.8% of cases above the 50pg/ug threshold and thus defined as positive. When compared to pathologist performed conventional ER classification, we found a false negative rate of 6.65% and a false positive rate of 10.2%, for a total misclassification rate of 16.6%. Although no response data is available on that cohort, data is under analysis on 4 other cohorts with endocrine therapy treatment information, including an independent Yale cohort, SWOG 9313, NSABP B14, and the TEAM trial.Conclusion: We have developed a quantitative method to measure absolute levels of ER in breast tissue. Use of this assay on a series of cohorts suggests a misclassification rate in the 15% range. The significance of this level of misclassification with respect to response to endocrine therapy is currently under study.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4068.
Aromatase Inhibitors (AIs) Versus Not (Placebo/Observation) as Late Extended Adjuvant Therapy for Postmenopausal Women with Early Stage Breast Cancer (BC): Overviews of Randomized Trials of AIs after ∼ 5 Years of Tamoxifen.
Authors: Goss P. , Mamounas E. , Jakesz R. , Markopoulos C. , Dowsett M. , Peto R. , Godwin J. , Davies C. 
Published: December 2010

Abstract
Backround: 5 yrs of adjuvant tamoxifen (Tam) substantially reduces recurrence and mortality in ER+ breast cancer. Two to five years of late extended AI (anastrozole, exemestane or letrozole) adjuvant therapy after ∼ 5 years of Tam has been studied in prospective trials in postmenopausal patients (pts) in comparison with placebo or observation.Methods: A meta-analysis of outcomes data submitted to EBCTCG was conducted for four clinical trial data sets: NCIC CTG MA17; NSABP B33; ABCSG VIA; ATENA. The primary analysis involved patients with tumors reported to be ER positive with endpoints of first BC recurrence (all, local only, contralateral BC only, distant), death with and without recurrence, any death. All p-values were 2-sided. Follow-up for MA.17 was censored at the date of un-blinding; this was not possible with B-33, which consequently includes some events following subsequent treatment crossovers.Results: Preliminary results are available; updated and sub-group analyses including progesterone receptor, age, grade and nodal status will be presented. Highlights include: at a median follow-up of 2.5 years, AI therapy was associated with an absolute 2.9% [standard error (SE) 0.5] decrease in BC recurrence [relative decrease, 43% (SE 8), p&lt;0.00001] and an absolute 0.5% (SE 0.3) decrease in BC mortality [relative decrease 27% (SE 17), 2p=0.11].Conclusions: A meta-analysis of 4 clinical trials, two of which were stopped early showed that ∼2-5 years late extended adjuvant therapy beyond 5 years from diagnosis produced a highly significant reduction in BC recurrence compared with no therapy. A trend toward improved survival is also seen. The magnitude of the effect seen on disease free and overall survival in these analyses is likely under estimated because of some cross-over after un-blinding. Longer than five years of adjuvant endocrine therapy is superior to just 5 years in ER+ breast cancer.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4081.
The Effect of Breast Cancer Diagnose on Cognitive Function.
Authors: Hedayati E. , Schedin A. , Albertsson M. , Nyman H. 
Published: December 2010

Abstract
Background: Women with breast cancer treatment complain about cognitive impairment. Previous studies indicate separately that receiving a breast cancer diagnosis has negative psychological impact and adjuvant treatment impairs cognitive functions. To investigate the impact on cognitive function is of great importance, since breast cancer is the most common cancer among women at working age in Sweden. We have started a longitudinal study to investigate if the effects of receiving a breast cancer diagnosis may affect cognitive functions. Materials and methods: The study is dimensioned for 148 subjects. The subjects were recruited consecutively and prospectively from the mammography-screening program at South Hospital, Stockholm. Those women who were recalled for further triple diagnosis assessment were invited to participate in our study. According to the results of the diagnostic process the patients were grouped in to: healthy women (n=69) and women with breast cancer (n=79). All participants were examined by a web-based battery of neuropsychological tests at inclusion (T1) and after diagnosis and subsequent surgery (T2). We measured four cognitive domains (Response speed, Processing speed, Memory and Attention). Results: Our results show that neither the healthy women nor patients with a recent breast cancer diagnosis with its subsequent surgery demonstrate any tendency toward a cognitive decline in any measured domains. The result did not differ significantly with regard to age, educational level or other demographic variables. Conclusions: The results may be interpreted to suggest that receiving a breast cancer diagnosis and/or surgery may not be associated to a substantial cognitive decline. Cognitive functions are not related with secondary depression and anxiety due to cancer diagnosis.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4091.
Validating CYP2D6 Genotype-Guided Tamoxifen Therapy for a Multiracial U.S. Population.
Authors: Irvin W. , Carey L. , Dees E. , Lange L. , Chiu W. , Evans J. , Anderson S. , Freidman K. , Weck K. , Desta Z. , Walko C. , Olajide O. , Raab R. , Corso S. , Peppercorn J. , Flockhart D. , McLeod H. 
Published: December 2010

Abstract
Background: Tamoxifen is a selective estrogen receptor modulator that is the most commonly used and cost effective agent for hormone sensitive breast cancer with documented efficacy in prevention, treatment of preneoplasia, and treatment in both the adjuvant and metastatic settings. However, tamoxifen is a prodrug, and up to half of those taking it may not receive the full benefit because of genetic differences in CYP2D6 that affect metabolism to its active form, endoxifen. Tamoxifen is FDA approved for use at both 20mg/day and 40 mg/day, however by convention is dosed at 20mg. We aimed to determine if endoxifen levels can be manipulated by genotype-guided dosing of tamoxifen.Methods: 118 patients on tamoxifen ≥ 4 months and not on potent CYP2D6 inhibiting medications enrolled in Lineberger Comprehensive Cancer Center (LCCC) trial 0801. Genotyping was performed using the CYP450 Amplichip® (Roche Diagnostics) for 2D6 alleles: *1-11, *15, *17, *19, *20, *29, *35, *36, *40, *41, *1XN, *2XN, *4XN, *10XN, *17XN, *35XN and *41 XN. Tamoxifen dose was increased from 20mg to 40mg in patients with any intermediate or poor metabolizing (IM or PM) alleles [but not in patients homozygous for extensive metabolizing (EM) alleles]. Endoxifen levels were drawn at baseline and 4 months later. Assuming that endoxifen levels in IM pts are 40% lower than EM at baseline (Jin et al., 2005) and with a one-sided significance level of 0.025 and a sample size of 40 patients with intermediate metabolizing CYP2D6 genotypes, this study would have 84% power to detect a 40% increase in endoxifen.Results: Of the 118 patients, 25 withdrew or were removed from study, leaving 93 who have completed this study and who are evaluable for the primary analysis. Genotyping results were presented at 2009 ASCO meeting (Irvin et al.). For this analysis, 19 (20%) are African-American, 69 (74%) are non-Hispanic white, 2 are Hispanic, and 3 are Asian. For the 93 evauable patients, genotyping revealed 31 (33%) EM/EM, 1 EM/UM (ultra-rapid), 20 (22%) EM/IM, 19 (20%) EM/PM, 4 (4%) IM/IM, 9 (10%) IM/PM, 9 (10%) PM/PM and 1 unknown. The primary outcome, the tamoxifen metabolite levels, including endoxifen, will be available in July.(Supported by NC University Cancer Research Fund, NCI SPORE, Laboratory Corporation of America, Roche Diagnostics)
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 410.
Evaluation of Fiducial Marker Migration and Respiratory-Induced Motion for Image Guided Radiotherapy in Whole Breast Irradiation.
Authors: Latifi K. , Forster K. , Harris E. 
Published: December 2010

Abstract
Purpose: Image guided radiation therapy (IGRT) may be beneficial to improve set up accuracy and reduce treatment margins, therefore improving efficacy while decreasing long term toxicity of whole breast irradiation (WBI). In order to assess if intraparenchymal fiducials can facilitate the use of IGRT, this study quantifies fiducial motion over the normal course of whole breast irradiation.Materials and Methods: On a prospective IRB-approved protocol, fiducials were placed in fourteen patients who were then treated with 3D conformal WBI. Three or four intraparenchymal gold fiducial markers were placed in each patient at the periphery of the surgical bed intraoperatively. Free breathing 4D CT image sets were obtained at pre-treatment simulation and then every two weeks over a six week course of treatment. Each fiducial marker was contoured at end-inspiration and end-expiration on all 4D CT image sets. The effects of respiration induced motion were assessed by comparing the positions of the fiducials between inspiration and expiration. Overall fiducial migration was determined by comparing the relative positions of each marker to one another from the pre-treatment and post-treatment 4D CT image sets.Results: The 4D CT image sets were acquired over a period of 55±4 days with a range of 49 to 60 days. The respiration induced fiducial motion, as measured by the average change in the fiducials' center of mass, was 0.8±0.6 mm with a range of 0 to 2.2 mm. The average fiducial displacement over the course of treatment as determined from relative seed position from the image sets was 1.5±1.2 mm with a range of 0.1 to 3.3 mm for all individual fiducials with 71% of the fiducials moving closer to each other and 29% away from each other.Conclusions: The preliminary results of using gold fiducials for breast IGRT are promising. Fiducial position was very stable during treatment, and there was very little respiration induced motion. Using IGRT, there is the potential to improve the accuracy of daily set-up and to reduce margins in WBI. Better tumor bed localization and reduced margin size will decrease the volume of normal tissue treated, which may translate into improved local control by ensuring accurate coverage of the target volumes throughout the treatment course and improvement in cosmesis and other long term toxicities.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4113.
The Effect of Radiotherapy on Local Regional Recurrence among Patients with Pathologic Complete Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.
Authors: Fasola C. , Godette K. , McDonald M. , O'Regan R. , Zelnak A. , Landry J. , Torres M. 
Published: December 2010

Abstract
Background: Radiotherapy has been shown to reduce local recurrence rates of breast cancer after treatment with surgery and adjuvant chemotherapy. Indications for postmastectomy radiation have historically been based on pathology, but indications for radiation in the setting of pathologic complete response (pCR) to neoadjuvant chemotherapy are not well defined. The aim of this study was to evaluate the rates of local regional recurrence (LRR) among patients with pCR to neoadjuvant chemotherapy followed by surgery with or without radiation (XRT).Patients and Methods: The case histories of 337 patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, surgery with or without radiation from October 1997 to December 2006 were analyzed. Median age at diagnosis was 50.6 years (range: 25-84). The clinical stage at diagnosis was I in 3 (1%), IIA in 105 (31%), IIB in 94 (28%), and III in 135 (40%) patients. All patients received preoperative systemic therapy with a doxorubicin-based regimen (92%) or a single-agent taxane regimen (7%) or CMF (1%). A total of 272 patients received radiation following surgery and 65 did not receive any radiation. Median follow-up time was 40 months among all patients. The Kaplan-Meier method and log rank test were used to evaluate LRR rates and overall survival among both groups.Results: Patients treated with neoadjuvant chemotherapy followed by surgery and XRT had a lower incidence of LRR at 3 years with 24 cases of local recurrence among 272 patients who received XRT compared with 12 cases of local recurrence among the 65 patients who did not receive XRT (8.9% v 18.5%, P=0.02). Radiation also reduced local regional recurrence at 3 years among a subset of patients with clinical stage T2N1 disease (4.9% v 28.6%, P=0.03). There was no difference in overall survival or disease free survival among patients who received XRT compared to patients who did not receive XRT. There were 62 (18%) patients who achieved a pCR to neoadjuvant chemotherapy. Among patients with a pathologic complete response, radiation appeared to reduce the risk of LRR compared to patients who did not receive XRT (7.4% v 25%, P=0.17).Conclusion: Radiotherapy significantly reduced local regional recurrence rate among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and surgery. Of particular interest, patients who achieve a pathologic complete response to neoadjuvant chemotherapy still had high LRR rates and may benefit from radiotherapy by lowering the risk of local regional recurrence. Further studies on the significance of LRR and overall survival among these patients are needed.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4114.