bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 amplification does not alter outcome in small (≤1 cm) tumors.
Authors: Ananthakrishnan P , Patrick RJ , Rybicki LA , Tubbs RR , Crowe JP , Budd GT 
Published: December 2010

Abstract
Abstract #6058
INTRODUCTION: Amplification of human epidermal growth factor receptor-2 (HER2) has been associated with an aggressive clinical phenotype, however the management of patients with small tumors (&lt;1 cm) that amplify HER2 is controversial. The goals of this study were: 1) to describe characteristics of HER2 amplified tumors based on tumor size, and 2) compare outcomes among 4 groups based on tumor size (small tumors &lt;1 cm or large tumors &gt;1 cm) and HER2 amplification (+ or -.)&#x2028; METHODS: Data were collected prospectively in our institutional review board approved breast center patient registry for patients with infiltrating ductal or infiltrating ductal-lobular mixed breast cancer. There were 770 patients with N0 tumors who were diagnosed between January 2001 and April 2005 (prior to treatment of HER2 amplified tumors with Trastuzumab). Categorical variables were compared using the Chi-squared test; outcomes were estimated using the Kaplan-Meier method and the log-rank test.&#x2028; RESULTS: At 4 years, estimated disease free interval was 97% in small HER2- tumors, 92% in large HER2- tumors, 91% in small HER2+ tumors, and 86% in large HER2+ tumors.&#x2028; &#x2028; At 4 years, breast cancer specific survival was 97% in small HER2- tumors, 92% in large HER2- tumors, 91% in small HER2+ tumors, and 86% in large HER2+ tumors.&#x2028; CONCLUSIONS: In our series, larger as opposed to smaller HER2+ tumors tended to be of higher histologic grade (SBR), and showed a trend toward more frequent lymphovascular invasion (LVI) and negative hormone receptor status. In small tumors, HER2 amplification did not predict recurrence-free survival or breast cancer disease specific survival at 4 years. The survival curves do show trends towards worsening outcomes for small tumors with HER2 amplification; these trends may show significance with additional follow-up.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6058.
A functional SNP in the leader sequence of the manganese superoxide dimutase gene is a predictor of breast cancer patient survival and response to chemotherapy.
Authors: Glynn SA , Boersma BJ , Howe TM , Ridnour L , Wink D , Edvardsen H , Børresen-Dale A , Ambs S 
Published: December 2010

Abstract
Abstract #6067
Background: A functional single nucleotide polymorphism (SNP) in the Manganese Superoxide Dismutase (SOD2) gene, characterized by a T-C transition located at codon 16, leads to a Val to Ala (Val16Ala) switch. The Val (T) allele disrupts the alpha-helix structure of SOD2 and causes the protein to be retained at the level of the mitochondrial inner membrane, with 30 to 40% lower activity and increased susceptibility to oxidative stress. We investigated whether the Val16Ala SOD2 polymorphism was associated with breast cancer survival.&#x2028; Methods: Two independent populations, one from the United States (n=244) and from Norway (n=329) were genotyped for the Val16Ala SOD2 polymorphism. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between the polymorphism and disease-specific survival, and response to chemotherapy.&#x2028; Results: We observed an association between Ala (C) allele and an increased risk of disease specific mortality. Carriers of the Ala/Ala genotype had an increased risk of poor survival in the combined analysis (Greater Baltimore and Norwegian datasets combined) when compared to carriers of Val/Val genotype using multivariate Cox regression analysis [Hazard ratio (HR) = 1.89; 95% confidence interval (CI), 1.16–3.07; p=0.011]. In the stratification analysis, the association was significant in those who underwent chemotherapy (HR = 2.54; 95% CI, 1.44–4.47; p=0.001), compared to those who did not (HR = 0.55; 95% CI, 0.16–1.94; p=0.353). Analysis by type chemotherapy received, showed that the Ala/Ala genotype had the strongest effect in patients receiving cyclophosphamide containing chemotherapy (HR = 18.88; 95% CI, 4.17–85.37; p&lt;0.001). Other drugs with an effect included 5-fluorouracil and doxorubicin. These results suggest that the Val16Ala SOD2 polymorphism may be a predictor of response to chemotherapy.&#x2028; Conclusion: We found that the Val16Ala SOD2 polymorphism, was associated with breast cancer survival, and is a potential predictor of response to chemotherapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6067.
Reductions in tumor RNA integrity associated with clinical response to epirubicin/docetaxel chemotherapy in breast cancer patients.
Authors: Parissenti AM , Chapman JW , Kahn HJ , Guo B , Han L , O'Brien P , Clemons MP , Jong R , Dent R , Fitzgerald B , Pritchard KI , Shepherd LE , Trudeau ME 
Published: December 2010

Abstract
Abstract #6068
Background: Optimal doses and dosing intervals for neoadjuvant anthracycline/taxane chemotherapy are poorly studied. Moreover, biomarkers for measuring response to such combination regimens are unknown. This study investigated these issues in sequential phase I/II cohorts of women with locally advanced or inflammatory breast cancer treated with epirubicin and docetaxel with pegfilgrastim support at 3- or 2-weekly intervals in association with the NCIC-CTG MA.22 clinical trial.&#x2028; Methods: Accrual has been completed for the 3-weekly regimen (maximum tolerated dose: epirubicin 105 mg/m2, taxotere 75 mg/m2), and continues for the phase II portion of the 2-weekly regimen. Six core biopsies were obtained from 50 patients pre-, mid-, and post-treatment. Immunohistochemical staining was performed to determine baseline levels of ER, PR, HER2 and Topo II expressed as % positive stain. Tumour RNA integrity (RIN) and tumor extent were measured pre-, mid- and post-treatment by capillary electrophoresis and light microscopy after haematoxylin/eosin staining, respectively. Associations between maximum and average RIN at the three time points and tumour extent, clinical response, pathologic complete response, or baseline levels of ER, PR, HER2 and Topo II were assessed using Spearman correlation coefficients after data transformation to improve symmetry and stabilize variances. The association between both RIN and tumour extent, and baseline drug dose was assessed using a 1-way ANOVA.&#x2028; Results: Low mid-treatment maximum RIN was associated with high drug dose level (p=0.05) and eventual pathologic complete response (p=0.01). Post-treatment, low maximum and average RIN were found to be associated with low tumor extent (p=0.004 and p=0.01, respectively). As well, low average RIN was significantly associated with clinical complete response post-treatment (p=0.01). As expected, post-treatment low tumor extent was significantly associated with pathologic complete response (p=0.01). High pre-treatment Topo II levels were also significantly associated with high RIN (p = 0.03). No association was observed between RIN and HER2, ER or PR.&#x2028; Discussion: The association of RIN with tumour extent, pathologic complete response, clinical response, a known risk factor (Topo II), and drug dose suggests that the RIN may represent an important new biomarker for measuring response to anthracycline/taxane combinations (and possible other chemotherapy regimens) in breast cancer patients.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6068.
HER2 amplification predicts breast cancer recurrence but not overall survival.
Authors: Ananthakrishnan P , Patrick RJ , Rybicki LA , Tubbs RR , Budd GT , Crowe JP 
Published: December 2010

Abstract
Abstract #6070
INTRODUCTION: Human epidermal growth factor receptor-2 (HER2) amplification has been associated with an aggressive breast cancer phenotype. The aims of this study were: 1) to determine if a relationship between HER2 amplification and local recurrence or overall survival (OS) existed; and 2) to compare prognostic effects of HER2 amplification with race, age, TNM stage, Scarff-Bloom-Richardson (SBR) grade, and hormone receptor status.&#x2028; METHODS: Data were collected prospectively in our institutional review board approved breast center patient registry for patients with infiltrating ductal or infiltrating ductal-lobular mixed breast cancer; all other histologic types, including pure infiltrating lobular, were excluded from this analysis. Variables analyzed included race, age at diagnosis, tumor size, overall TNM stage, SBR grade, HER2 status, and hormone receptor status. Outcomes were defined as disease-free survival (local and distant) and OS. The prognostic effect of HER2 amplification on disease-free survival (DFS) and OS was assessed after adjusting for race, age, TNM stage, SBR grade, and hormone receptor status; Cox proportional hazards analysis was used in the multivariable analysis. A stepwise selection procedure was used in the multivariable analysis with p&lt;0.10 required to allow a variable into the model and p&lt;0.05 required to retain it in the final model. &#x2028; RESULTS: Data were available for 1750 patients (mean age at diagnosis 60 years) diagnosed between January 2001 and July 2007; mean tumor size 1.8 cm, of which 384 (22%) were hormone receptor negative and 296 (17%) were HER2 amplified. Risk factors for DFS included HER2 amplification (Table 1), black race, increasing TNM stage, and negative hormone receptors. Risk factors for OS included black race, increasing TNM stage, and negative hormone receptors. HER2 amplification was associated with decreased disease-free survival (Fig 1a) but not OS (Fig 1b).&#x2028; &#x2028; &#x2028; &#x2028; CONCLUSIONS: Although HER2 amplification predicted disease-free survival, it did not predict OS in the multivariable analysis. A possible explanation for this finding is the increasing use of Trastuzumab for HER2 amplified tumors after relapse.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6070.
Immunoglobulin G fragment C gamma receptor (FcGR) polymorphisms and efficacy of single-agent trastuzumab in patients treated with metastatic breast cancer.
Authors: Shimizu C , Tamura K , Koizumi F , Aogi K , Kinoshita T , Fujiwara Y 
Published: December 2010

Abstract
Abstract #6073
Background: Antibody-dependent cell-mediated cytotoxicity (ADCC) may be involved in antitumor effect of therapeutic monoclonal antibodies and their effector functions are induced following the interactions of IgG with FcGR. Studies have shown that FcGRIIIa-V158F and FcGRIIa-H131R polymorphisms may predict response to retuximab, cetuximab in patients with follicular lymphoma, colorectal cancer, and recently, trastuzumab-combined chemotherapy in breast cancer patients (J Clin Oncol 25; 1789, 2008). We tested the hypothesis of whether these two polymorphisms are associated with clinical outcome in metastatic breast cancer patients treated with single-agent trastuzumab treatment.&#x2028; Patients and Methods: Patients with HER2-positive (HercepTest (3+) or (2+) with gene amplification either in primary or metastatic site) metastatic breast cancer were enrolled onto this prospective study. Eligible patients were hormone receptor negative or endocrine therapy resistant, and had received no prior chemotherapy for metastatic disease. Study patients received single agent trastuzumab at a loading dose of 4 mg/kg followed by 2 mg/kg per week until disease progression. The first clinical response was assessed at 8 week. FcGRIIIA-V158F and FcGRIIA-H131R genotypes were assessed from genomic DNA extracted from peripheral blood samples. The present study has been approved by the institutional review boards of National Cancer Center and Shikoku Cancer Center Hospital and all registered patients have given written consent to participate in this study.&#x2028; Results: To date, 33 patients have been enrolled. The frequency of FcGRIIIa-V158F genotypes were V/V 48%, V/F45%, F/F 6%, and that of FcGRIIA-H131R genotypes were H/H 59%, H/R38%, R/R 3% , respectively. 8-wk response could be evaluated in 29 patients (CR 1, PR 4, SD 13, PD 11). Clinical benefit was observed in 13 patients (CR 1, PR 6, SD&gt;6months 6). FcGRIIIa-158V/V genotype was significantly correlated with 8-wk response (p=.017) and clinical benefit (p=0.02) of single-agent trastuzumab, while there was no significant difference in clinical response to trastuzumab by FcGRIIA-H131R polymorphism.&#x2028; Conclusion: Although still preliminary, these data support the previous finding that FcGRIIIa-V158F polymorphisms play an important role in the clinical activity of trastuzumab. Updated results will be presented at the 31st annual San Antonio Breast Cancer Symposium.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6073.
Breast cancer in the United States: the burden on an aging, changing nation.
Authors: Smith BD , Smith GL , Hurria A , Buchholz TA 
Published: December 2010

Abstract
Abstract #6076
Background: Over the next 20 years, important demographic changes in the US will emerge, with the number of older and non-white Americans increasing dramatically. Though breast cancer incidence is known to vary by both age and race, the projected impact of impending population changes on breast cancer incidence has never been quantified. To delineate the future burden of breast cancer, we calculated population-based projections of breast cancer incidence through 2030.&#x2028; Material and Methods: SEER data provided current age- and race-specific incidence rates for invasive or in situ female breast cancer. Age- and race-specific projections for the US population through 2030 were derived from Census Bureau data. Assuming stable race- and age-adjusted incidence, the total number of breast cancer cases by race and age through 2030 was estimated.&#x2028; Results: From 2008 to 2030, the total number of breast cancer cases is expected to increase from 264,000 to 357,000. Of cases diagnosed in 2030, 60% will occur in women ages 65 and older. This represents a 67% increase in the number of breast cancer cases in women age 65 and over (from 127,000 to 212,000), compared to a 6% increase in women under age 65 (from 137,000 to 145,000). In 2030, 19% of all cases will occur in non-whites, representing a 70% increase in non-whites (from 40,000 to 68,000), compared to a 29% increase in whites (from 224,000 to 289,000). While cases in older non-white women currently represent only 13% of older patients, they will comprise 17% by 2030.&#x2028; Discussion: With major demographic shifts on the horizon, an imminent wave of older breast cancer patients will impose a substantial burden on the US healthcare system. Efforts to expand capacity, contain cost, and define optimal treatment for older patients are urgently needed. Moreover, the projected increase in the percentage of breast cancer in non-whites heightens the importance of efforts to identify and minimize health care disparities.&#x2028; &#x2028;
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6076.
Breast cancer in the elderly: histoclinial features and phenotypical characterization on tissue microarrays (TMA).
Authors: Jauffret EA , Boher J , Esterni B , Rousseau F , Jacquemier J , Viens P 
Published: December 2010

Abstract
Abstract #6079
Most breast cancer patients are diagnosed over the age of 65 years, and older cancer patients represent an increasing major public health problem. Research efforts are mainly focused on younger patients and the elderlies are initially excluded from most clinical trials. Improving kwnoledge related to elderly breast caner is urgently needed.734 patients over the age of 70 years out of the 4503 treated in our institution for primary breast cancer from 1975 to 2006 were studied. Pathological data revealed 716 (97.5%) invasive breast cancers, and 633 (88.5%) of ductal type including only 31 (8%) with predominant ductal in situ component. Lobular and mucinous carcinomas were present in11.5 and 3.5%.The tumors were mostly medium size (pT2); displayed no differences in lymph node involvement compared to younger patients and were treated by surgery (680, 93%) with 338 (50%)mastectomy, and with chemotherapy in only 22% (vs 48% in younger). Compared to youngers, tumors were mostly grade II (47%) and displayed less grade III ,estrogen receptors were expressed in 73% and tumors were less proliferative as assed on KI67/Mib1 expression (28 vs 38% positive &lt;70 years) . Phenotypic characterization was done on Tissue-microarrays containing 305 spotted breast samples from patients over the age of 70 for 28 differents markers corresponding to different pathways : adhesion molecules (E-cadherin, p-cadherin, b-catenin), cell cyle and mitosis (fox a1, Ki67, p53, p27 ), differentiation markers (luminal CK8/18, basal/mesenchymal CAV1 &2, CK5/6, CK14, moesin, S100A9, SMA, vimentin, and stem cell markers ALDH1 and CD44), hormonal (hormonal and androgen receptors, bcl2, gata3), tyrosine kinases (ERBB2, EGFR), angiogenesis (angiogenin, CD146,VEGF) pathways. Compared to younger, no marker was significantly different in patients older than 70, except for hormonal pathway (a tendancy to be more positive). Nevertheless, specific survival and metastasis free survival (considering chemotherapy) revealed a worst outcome for older patients. Cox 's univariate model revealed claasical prognostic factors (hormonal pathway,ERBB2, EGFR, Mib1/Ki67) but did not highlight specific pathways. In conclusion, breast cancer in the Elderly is an heterogenic group that display less aggressive histo clincal features, a little more ER-phenotype with less proliferation but an adverse outcome. Specific factors remains to be discover to better treat these patients.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6079.
Breast cancer mortality trends in the WEST compared to the EAST: lives gained, lives lost.
Authors: Ragaz J , Bao P , Pisani P , Zheng Y 
Published: December 2010

Abstract
Abstract #6082
INTRODUCTION: Breast Cancer (BrCa) Mortality trends between 1950 – 2005 were reviewed between the Western (WEST) and Eastern Asian (EAST) countries, with the objective to gain understanding between therapeutic and diagnostic interventions and underlying epidemiology factors determining BrCa outcomes.&#x2028; METHODOLOGY: We compared BrCa mortality trends in the WEST (Canada, UK, USA) and in the EAST (Japan and China-Shanghai). Data were obtained from WHO - IARC, Lyon (Canada, USA, UK, Japan); and from the Shanghai Cancer Registry (China-Shanghai). We analyzed age-standardized annual mortality rates per 100,000 / population (as per 1960 world standard population). Mortality trends were expressed relative to the baseline (year 1950 for all, year 1973 for China-Sha).&#x2028; RESULTS: The baseline mortality rates were: 22.5 for Canada; 23.5 for UK; 21.6 for USA, 4.1 for Japan; and 7.3 for China-Shanghai.&#x2028; &#x2028; CONCLUSION. These data confirm a substantial mortality reduction in the WEST evident after the 1980's - 1990's, likely reflecting the interaction of diagnostic and therapeutic interventions (mammography, education, systemic / locoregional therapies, etc). The different timing and extent of mortality reduction in the WEST probably reflect different degree of implementation of the interactive factors.&#x2028; On the other hand, mortality is increasing in the EAST, in parallel with the “westernization” of those regions (industrialization, diet, etc, Ref. [NEJM; 2008:358;3)]. For the EAST, our data also support a correlation between the timing / extent of the “westernization” and mortality trend dynamics (i.e. mortality increase in Japan 20 years earlier than China).
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6082.
Low penetrance breast cancer predisposition SNPs are site specific.
Authors: Mc Inerney NM , Colleran G , Walther A , Rowan A , Spain S , Jones AM , Tuohy S , Barclay E , Curran C , Miller N , Kerin MJ , Tomlinson I , Eli S 
Published: December 2010

Abstract
Abstract #6085
Introduction&#x2028; A locus on chromosome 8q24.21 has been shown to harbours variants that predispose to breast cancer, colorectal cancer and prostate cancer. The finding of risk variants clustering at 8q24 suggests that there may be common molecular mechanisms that predispose to the common epithelial cancers. The aim of this study was to determine whether the colorectal and prostate susceptibility alleles on 8q24 and other recently identified colorectal and prostate susceptibility alleles elsewhere in the genome are also associated with breast cancer risk.&#x2028; Methods&#x2028; In this study, we have studied three SNPs on 8q24.21: the breast cancer susceptibility SNP, rs13281615; the colorectal/prostate cancer susceptibility SNP, rs6983267; and the prostate susceptibility SNP, rs16901979; and eleven other SNPs outside of this region that have recently been shown to predispose to either prostate or colorectal cancer. Each SNP was genotyped in 988 sporadic breast cancer cases and 1016 controls from the West of Ireland using KASPar genotyping technology. We combined our data with publicly available datasets (breast: CGEMS, Fletcher et al.; prostate: CGEMS, Eeles et al.; CRC: Tomlinson et al.) by allelic, genotypic, dominant and recessive models using standard techniques of meta-analysis for SNPs previously identified to confer an increased cancer risk in specific tissue types. All analyses were done in Stata 9.2 (Stata Corp, TX).&#x2028; Results&#x2028; rs13281615 was associated with breast cancer (Pallelic test= 1.8 -2) with an odds ratio of 1.17. However there was no association between any of the prostate or colorectal susceptibility SNPs at 8q24 or elsewhere with breast cancer risk in our cohort. The data support the existence of a low-penetrance susceptibility locus for breast cancer near rs13281615; this locus seems to be distinct from the prostate and colorectal cancer loci in that region, even if the functional effects of the predisposition loci affect the same target gene or protein. Meta-analysis did not show an association between reported cancer SNPs and cancers in other tissue types.&#x2028; Conclusions&#x2028; This study suggests that low penetrance susceptibility SNPs for breast, colorectal and prostate cancer are distinct and argues against the presence of ''general' cancer predisposition SNPs. Although 8q24 harbours variants that predispose to all three cancers the susceptibility loci within the region appear to be specific for the different cancer types.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6085.