bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Expression Profiling for Therapy Prediction in a Breast Cancer Neoadjuvant Therapy Study Applying Docetaxel/Epirubicin/Cyclophosphamide.
Authors: Kemming D. , Schlotter C. , Bosse U. , Vogt U. , Muhs H. , von der Assen A. , Brandt B. 
Published: December 2010

Abstract
Background: Gene expression profiling is a powerful tool to identify markers associated with clinical and therapy outcome of cancer patients. Prediction of the response to neoadjuvant regimens remains a persistent challenge. Aim of this ongoing study is the development of a gene set predicting the response of the tumor to a taxane- anthracycline based neoadjuvant chemotherapy.Material and Methods: Microarray expression profiling was performed on biopsy samples from patients before treatment using Human Genome Survey microarrays (HGSM). The protocol for a phase II study was elaborated for the treatment of breast cancer patients suffering from a primary tumor 1.5 cm or inflammatory breast cancer with Docetaxel/Epirubicin/Cyclophosphamide (TEC) prior to surgical treatment. The study was approved by the local ethical committee and all patients signed an informed consent.Results: Overall 80 patients have been enrolled in the presented study. High quality gene expression data were available from 58 patients. Of these patients 21 responded to the TEC regimen (pCR or MIB1 expressing cells in the residual tumor &lt;= 5% and decrease of Mib1-expression &gt;= 20%). Based on the gene-expression profile we were able to identify a preliminary gene set of 150 genes which allows us to separate responding tumors from the non responding ones based on their gene expression profile. A comparable separation of the groups could not achieved by established tumor markers, e.g. ER, PgR, HER2, uPA etc. which are measured simultaneously on the HGSM. Among the genes distinguishing the two groups several genes normally expressed in mononuclear blood cells were identified, pointing to the presence of tumor infiltrating leukocytes, predominantly in the tumors responding the TEC regimen. The presence of these cells has already been verified in a subset of the samples.Conclusion: We identified a gene set which allows to select patients who will benefit from neoadjuvant chemotherapy. Furthermore at least in the so far investigated samples tumor infiltrating leukocytes are significantly more often found in tumors which respond to a taxane- anthracycline based neoadjuvant chemotherapy.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2039.
Expression of Gene Trios as Predictive Markers of Response to Doxorubicin Based Primary Chemotherapy in Breast Cancer Patients.
Authors: de Camargo Barros Filho M. , Katayama M. , Brentani H. , Abreu A. , Oliveira C. , Góes J. , Barbosa E. , Brentani M. , Folgueira M. 
Published: December 2010

Abstract
Some studies have been carried out to identify a gene expression profile predictive of drug response in breast cancer patients and assessed the reproducibility of the model in an independent group of patients. In common, these studies have used the same technique already used to identify the panel of genes in a training set, to verify accuracy of the model in a validation set. We have previously identified through cDNA microarray technology gene trios whose expression was capable of predicting response to neoadjuvant chemotherapy based in doxorubicin and cyclophosphamide in breast cancer patients. We have now evaluated whether expression of these genes analyzed by real time RT-PCR, which represents a more accessible technique, would reproduce cDNA microarray results in separating responsive from non-responsive patients. Twenty eight samples, already studied by cDNA microarray, were analyzed as a technical validation group and subsequently, another 14 samples were evaluated, as a biological validation group. Expression of nine genes (defining five trio combinations, previously identified) was evaluated by RT-PCR in samples from the technical validation group, to define the separating plane, using linear discriminant analysis. Among the five trios, the best separation of tumors was conferred by RPL37A, XLHSRF-1 based trios (with NOTCH1 or NUP210, as third genes), which correctly classified 86% of samples from the technical validation group and 82% in a cross-validation analysis (leave-one-out). Next, samples from the biological validation group were spatially distributed using the pre-established features from these two trios, resulting in 71% correct classification. Additionally, other gene combinations were searched for a higher accuracy in discriminating response and expression of a new trio, RPL37A, SMYD2 and MTSS1, correctly classified 86% and 79% of samples from the technical validation (leave-one-out cross-validation) and the biological validation groups, respectively. Expression values evaluated by cDNA microarray and RT-PCR are reproducible, however they are not exactly the same as these methods are based on different technical principles and normalization approaches. Our data indicate that care should be taken when substituting techniques in an attempt to reproduce a model. In conclusion, expression of the gene trio RPL37A, SMYD2, MTSS1, as evaluated by RT-PCR, is a potential candidate as predictive marker of response to neoadjuvant chemotherapy in breast cancer patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2040.
Outcome of Invasive Lobular Carcinoma Compared to Infiltrating Ductal Carcinoma: A Population Based Study from British Columbia.
Authors: Al-Foheidi M. , Speers C. , Woods R. , Kennecke H. , Kennecke H. , Chia S. , Chia S. 
Published: December 2010

Abstract
Background: Lobular carcinoma is the 2nd most common invasive breast cancer histology after ductal carcinoma. Though phenotypically they are different, the two histologies are often treated the same with presumed similar outcomes. We sought to compare the baseline demographics, standard pathologic factors and long term clinical outcomes between lobular and ductal carcinoma from a large population based breast cancer registry.Methods: A retrospective cohort of referred patients to the BCCA with a diagnosis of stage I-III pure lobular or pure invasive ductal carcinoma from 1989-2000 was identified. Prior or synchronous breast cancers and cases with unknown grade were excluded. Standard demographic and pathologic factors was abstracted from the BCCA Breast Cancer Outcomes Unit database and compared between the two histologies. 10 year outcomes were calculated by Kaplan Meier method, with differences compared by log rank test. Median follow up for the entire cohort was 9.3 years.Results: A total of 13,203 individual patients meeting identified inclusion criteria were identified: 11,911 invasive ductal and 1,292 invasive lobular cancers. Lobular carcinomas generally had a higher frequency of poor prognostic factors: older age (≥ 70 years old), larger tumour size, and greater frequency of N2 nodal involvement (all p&lt;0.001). However lobular carcinomas also had a higher frequency of better predictive factors: ER+ status and low grade tumours (both p&lt;0.001). There were differences in locoregional treatments and systemic therapies between the groups. No differences were seen at 10 year estimated relapse free survival (76% vs 74%), distant RFS (78% vs 77%), breast cancer specific survival (81% vs 81%) and overall survival (69% vs 70%) between lobular and ductal cancers respectively. Only 10 year locoregional RFS significantly favored lobular cancers (93% vs 89%; p&lt;0.001), though there was also a higher mastectomy rate (55% vs 39%) in this cohort.Conclusion: Though invasive lobular carcinomas are epidemiologically and phenotypically different from ductal carcinomas, clinical outcomes are comparable between these two common histologies.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2046.
Characteristics of Overall and Cause-Specific Survival Rates in Breast Cancer Patients under the Age of 40: A Population Based Study of 481,294 Cases in SEER Registry.
Authors: Kim E. , Thomas, Jr C. , Hoffelt C. 
Published: December 2010

Abstract
Background: Age at diagnosis has been shown to be an important prognostic factor of outcome for breast cancer (BCA). The specific aim of this study was to determine the overall survival (OS) and cause-specific survival (CSS) in young patients (&lt;40 years old) with BCA relative to older age groups.Methods & Materials: The population of this study comprised of the 481,294 cases of women with BCA extracted from the Surveillance, Epidemiology, and End Results (SEER) registry from 1973-2006, and restaged BCA cases according to AJCC 6th edition staging system. OS and CSS were determined by the Kaplan-Meier method using R. Statistical significance was tested using the log rank or Mantel-Haenszel test in R.Results: The total 481,294 cases were categorized into the following stage groups: Stage 0 (36,692, 7.6%), I (243,460, 50.6%), II (135,013, 28.1%), III (50,233, 10.4%), and IV (15,896, 3.3%). The range of ages was from 11 to 106 (mean 60.5). Ages were divided into 5 groups: &lt;40 (25,918, 5.4%), 40-49 (89,712, 18.6%), 50-59 (116,548, 24.2%), 60-69 (110,536, 23.0%), and &gt;69 (138,580, 28.8%) years old. A graph of OS and tables for OS and CSS from Kaplan-Meier analysis of the entire cohort (all stages) is shown below:OS (all stages) by Age GroupAges \ OS5-year10-year15-year&lt;40.849.764.71440-49.899.830.77550-59.890.810.72560-69.863.728.576≥70.731.479.253 CSS (all stages) by Age GroupAges \ CSS5-year10-year15-year&lt;40.680.785.74240-49.913.859.82550-59.914.864.82560-69.916.860.814≥70.887.820.762 Both OS and CSS of each stage group shared the same trends as in the analysis of the entire cohort.Conclusion: The OS of the &lt;40 year age group was statistically significantly better than the 60's and &gt;69 year age groups, but worse than the 40's and 50's age groups. The CSS of the youngest age group was significantly worse than all age groups except the &gt;69 age group. Further studies to determine contributing variables for these observatios is warranted.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2048.
Breast Cancer Survival of Elderly Women in the Netherlands (1994-2005).
Authors: Bastiaannet E. , de Craen A. , Liefers G. , van der Geest L. , Westendorp R. , van de Velde C. 
Published: December 2010

Abstract
Purpose of the study: Breast cancer is the most commonly diagnosed malignancy in elderly women. With an increasing life expectancy of Western populations and increasing incidence of breast cancer, it is one of the major health concerns in the geriatric population. Aim of this study was to assess time trends in relative survival of elderly breast cancer patients in the Netherlands as compared to the younger patients and compare expected and observed mortality in the Dutch population.Methods: Female breast cancer patients 15 years and older, diagnosed with their first primary breast cancer from 1994-2005, were selected from the Netherlands Cancer Registry (NCR). Relative survival was calculated by the Hakulinen method as the ratio of the survival observed among the cancer patients and the survival that would have been expected based on the corresponding (age and year) general population. National life tables were used to estimate expected survival. Relative Excess Risks of death (RER) over time according to age were estimated using a multivariate generalized linear model with a Poisson distribution, based on collapsed relative survival data, using exact survival times.Results: Overall, 127 805 patients were included. Relative survival (5-years) declined from 87.1% for 15-65 years old to 86.1% (65-74), 74.7% (75-84) and 68.4% for 85 years and older. From 1995-2005 relative survival did increase for the young patients (RER corrected for stage, histology, treatment and grade 0.93; p&lt;0.001) and for 65-69 (RER 0.93; p&lt;0.001), 70-74 (RER 0.97; p=0.005) and 75-79 (0.98; p=0.03) years old. However, relative survival did not increase significantly for elderly patients of 80 years and older. Relative survival was higher for patients younger than 70 years and the difference in (corrected) RER for elderly versus young patients did increase over the years from 1.22 to 1.69 (p&lt;0.001). Stratified for stage the differences were most striking in the higher stages. Differences between observed and expected mortality decreased with increasing age.Conclusion(s): The gap in breast cancer survival between young and elderly (&gt;70) patients has increased in the Netherlands and survival for patients of 80 years and older has not improved. Despite growing degree of interest, internationally agreed evidence-based guidelines for the elderly with breast cancer do not exist. The aim of the FOCUS study that recently started in the Netherlands is to develop clinical guidelines for the elderly females with breast cancer using population-based, clinical trial and molecular data.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2052.
Physical Activity Levels of Women Attending Glasgow Breast Clinics.
Authors: Tan A. , Pavlidou E. , Ogston K. , Doughty J. , Wilson C. , Campbell A. , Tovey S. 
Published: December 2010

Abstract
IntroductionEpidemiological studies suggest that moderate intensity recreational physical activity (PA) improves breast cancer survival. We aimed to assess the current levels of PA in breast cancer survivors and a cohort of women with benign disease attending clinics in Glasgow.Materials and MethodsPatients at breast clinics at the GRI and WIG were recruited over a 5 week period. Data on physical activity levels (occupational, household, recreational) over the 7 days were recorded using the International Physical Activity Questionaire (IPAQ).ResultsA total of 352 patients were recruited with 141 (40.1%) of the patients completing the questionnaire successfully (table 1).Table 1 Women attending symptomatic clinicBreast cancer survivorsNo. patients 9742Median Age 4263Average physical activity levels (MET-Hr / Week)Total11493.4 Physical19.619.7 Household35.740.0 Occupational40.523.9 Recreational PA appears to be the major influence on breast cancer survival (1) and the reported MET-hr/week for each cohort are shown in table 2.Table 2Recreational Physical activity levels (MET-Hr / Week)Women attending symptomatic clinicBreast cancer survivors&lt;533 (34%)21 (50%)5 - 1014 (14%)5 (12%)10 - 1918 (19%)8 (19%)&gt;1932 (33%)8 (19%) DiscussionScottish guidelines (2) suggest 30min of moderate exercise most days a week is beneficial (&gt;10MET-hr/week) but over 60% of our patients were not achieving this. A recreational PA level of &gt;5MET/hr/week has been demonstrated to confer a benefit on breast survival (1). However 50% of our breast cancer survivors are not meeting this relatively modest target (equivalent to 1hr15min moderate activity/week). With the planned implementation of an exercise programme for all newly diagnosed breast cancer patients in Glasgow, we hope to improve levels of recreational physical activity and will re-audit following its introduction.References1. Friedenreich CM, Gregory J, Prospective cohort study of lifetime physical activity and breast cancer survival. Int J Cancer. 2009 Apr 15;124(8):1954-622. Let's Make Scotland more active: A strategy for physical activity. Physical activity task force http://www.scotland.gov.uk/Publications/2003/02/16324/17895 [Online March 2009]
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2066.
Male Breast Cancer: A Population-Based Comparison with Female Breast Cancer.
Authors: Anderson W. , Jatoi I. , Rosenberg P. 
Published: December 2010

Abstract
Purpose: Because of its rarity, male breast cancer is often compared to female breast cancer.Materials and Methods: To compare and contrast male and female breast cancers, we obtained case and population data from the NCI's Surveillance, Epidemiology, and End Results program for breast cancers diagnosed from 1973 through 2005. Standard descriptive epidemiology was supplemented with age-period-cohort models and breast cancer survival analyses.Results: Men with breast cancer comprised less than 1% of all breast cancers. Male compared to female breast cancers occurred later in life with higher stage, lower grade, and more estrogen receptor positive tumors. Recent breast cancer incidence and mortality rates declined over time for men and women, both overall and within each age group, but these trends were greater for women than men. Comparing cases diagnosed in 1996 through 2005 versus 1976 through 1985, and adjusting for age, stage, and grade, cause-specific hazard rates for breast cancer death declined by 28% among men (p = 0.03) and by 42% among women (p ∼ 0).Conclusion: There were three intriguing results. Age-specific incidence patterns showed that the biology of male breast cancer resembled the late-onset and hormone sensitive type of female breast cancer. Similar breast cancer incidence trends among men and women suggested that there are common breast cancer risk factors that affect both sexes, especially hormone positive breast cancer. Finally, breast cancer mortality and survival rates have improved significantly over time for male breast cancer, but progress has lagged behind for men compared to women.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2075.
Sensitivity to Taxane Chemotherapy for Metastatic Breast Cancer in BRCA1 and BRCA2 Mutation Carriers Compared to Sporadic Breast Cancer Patients.
Authors: Seynaeve C. , Jager A. , Hooning M. , den Bakker M. , Bontenbal M. , Blom J. , Collee M. , van den Ouweland A. , Kriege M. 
Published: December 2010

Abstract
Purpose: Data of in vitro and small retrospective studies suggest that breast cancer (BC) (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to chemotherapeutic agents causing double strand DNA breaks, while sensitivity to spindle poisons, such as paclitaxel and docetaxel, has been found to be decreased. Clinical data on the latter, however, are very scarce. In this study, we assessed the sensitivity to taxane chemotherapy for metastatic BRCA1/2-associated compared with sporadic breast cancer.Methods: From the family cancer clinic database, we retrieved 36 BRCA1 and 13 BRCA2-associated BC patients treated with taxane chemotherapy for metastatic disease before October 1, 2008, and with available data on follow-up and response assessment. Objective response (OR), and progression-free survival (PFS) after start of taxane chemotherapy were compared with those of 62 sporadic patients with comparable age at diagnosis and year of detection of metastatic BC. A t-test or chi-square test was used to test for differences in characteristics and response types, and Kaplan-Meier survival analysis to calculate PFS.Results: Taxane chemotherapy consisted of docetaxel (n= 76) or paclitaxel (n=21), while 10 (9%) patients received a taxane/trastuzumab regimen. It was given as first-line palliative therapy in 9 BRCA1, 1 BRCA2 and 22 sporadic patients; but mainly as second/third line treatment (BRCA1 n=27, BRCA2 n=12, sporadic patients n=40, respectively). As compared to sporadic patients, BRCA1-associated patients had a significantly lower OR rate (ORR) overall (22% vs 46%, p&lt;0.001) and to 2nd/3rd line taxane treatment (19% vs 46%, p&lt;0.001). Median PFS was shorter in BRCA1 patients (2.0 vs 4.1 mo, p=0.08), with a trend for significance for 2nd/3rd line therapy (1.6 vs 3.9 mo, p=0.05). Also, compared to BRCA2 patients, the ORR in BRCA1 patients was significantly lower, overall as well as to 2nd/3d line therapy (both p=0.003). In BRCA2 mutation carriers compared to sporadic patients, the ORR was higher (75% vs 48%, p=0.28) and PFS longer (6.4 vs 4.1 mo, p=0.33). After exclusion of the patients receiving a taxane/trastuzumab schedule, similar data were observed.Conclusion: Objective response rate to taxane chemotherapy for metastatic disease is lower in BRCA1-associated BC in comparison with sporadic as well as BRCA2-associated BC, resulting in a shorter PFS. If confirmed, these data may have substantial clinical relevance.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2098.
Zoledronic Acid Prevents Bone Loss in Premenopausal Women with Early Breast Cancer Undergoing Adjuvant Chemotherapy: A Phase III Study of Korean Cancer Study Group (KCSG-BR06-01).
Authors: Ahn J. , Jung K. , Kim S. , Lee K. , Ro J. , Park Y. , Ahn J. , Im Y. , Im S. , Lee M. , Kim S. 
Published: December 2010

Abstract
Background: Adjuvant chemotherapy results in early menopause in the majority of premenopausal patients due to premature ovarian failure and consequent skeletal morbidity. Zoledronic acid (ZA) is known to prevent bone loss in postmenopausal women. The purpose of this study was to determine whether ZA can prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.Methods: This study is a randomized, open-label, phase III multicenter trial. Premenopausal women older than age 40 were randomly assigned to ZA group (two infusions of 4 mg IV, every 6 months) or observation group after surgery. All patients were treated with the same adjuvant chemotherapy regimen (AC--&gt;T; 4 cycles of AC followed by 4 cycles of paclitaxel or docetaxel). The first infusion of ZA was given on day 1 of the first chemotherapy. All patients received supplementations with oral calcium 600 mg/d and vitamin D 400 IU/d. The bone mineral density (BMD) was measured at the baseline, 6th and 12th months. Bone turnover markers were measured before chemotherapy and in 3, 6, 12 months.Results: Between March 2007 and May 2008, a total of 110 premenopausal women were enrolled in this study and the majority of women (91.8%) developed amenorrhea at 1 year post chemotherapy. The mean percent change of BMD in lumbar spine was +0.5% in the ZA group versus -3.6% in the observation group at 6 months (p&lt;0.01) and, -1.0% versus -7.5%, at 12 months (p&lt;0.01). Differences in percent change of BMD from baseline between two groups were 6.5% (95% CI, 5.2 to 7.9%) for the lumbar spine, and 3.6% (95% CI, 2.2% to 5.1%) for the femoral neck (p&lt;0.01). Type I collagen metabolite PINP levels at 12 months were significantly higher in the observation group than in the ZA group; 72.7 mg/l (range 21.8∼250 mg/l) versus 30.8 mg/l (range 14.7∼62.7 mg/l) (p=0.0001). Changes of other bone turnover markers including urinary N-telopeptide, bone alkaline phosphatase, and serum C-telopeptide were also significantly different between two groups (p&lt;0.01). ZA was generally well tolerated, and adverse event profile was similar between two groups.Conclusion: Adjuvant chemotherapy with AC--&gt;T induced amenorrhea in the majority of patients over 40 years in this study. Treatment with two infusions of ZA 4 mg every 6 months effectively prevented bone loss within the first year of adjuvant chemotherapy for early breast cancer in premenopausal women. Regular BMD measurements and early bisphosphonate therapy should be considered for this population.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2104.