2014
Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer
Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo JA, Cristofanilli M, Gómez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross JS, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Brown M, Miller VA. Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer. Clinical Cancer Research 2014, 20: 1757-1767. PMID: 24398047, PMCID: PMC3998833, DOI: 10.1158/1078-0432.ccr-13-2332.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsEstrogen Receptor alphaFemaleHigh-Throughput Nucleotide SequencingHumansMCF-7 CellsMutationNeoplasm StagingNeoplasms, Hormone-DependentConceptsEstrogen receptor α mutationBreast cancerAdvanced estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerHormone-dependent breast cancerPrimary breast cancerSubgroup of patientsER-negative tumorsLine of treatmentCodon 537ER- diseaseEndocrine treatmentTreatment-naïveESR1 mutationsMetastatic diseaseCell line modelsEndocrine resistanceMetastatic tumorsReceptor constitutive activityEstrogen receptorMetastatic samplesTumor specimensCancer-related genesNatural history
2012
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer
Liu JC, Voisin V, Bader GD, Deng T, Pusztai L, Symmans WF, Esteva FJ, Egan SE, Zacksenhaus E. Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5832-5837. PMID: 22460789, PMCID: PMC3326451, DOI: 10.1073/pnas.1201105109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCalcium-Binding ProteinsCD24 AntigenCell DifferentiationCell DivisionEstrogen Receptor alphaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansIntercellular Signaling Peptides and ProteinsJagged-1 ProteinMembrane ProteinsMiceNeoadjuvant TherapyNeoplastic Stem CellsPrognosisReceptor, ErbB-2Serrate-Jagged ProteinsSignal TransductionTrastuzumabTreatment OutcomeConceptsTumor-initiating cellsMammary tumor-initiating cellsBreast cancerClinical outcomesPrognostic signatureHuman epidermal growth factor receptorAnti-HER2 drugsAnti-HER2 therapyHigh-risk patientsHigh-risk subgroupsEpidermal growth factor receptorGrowth factor receptorBC cohortRisk patientsAggressive diseaseBC patientsRetrospective analysisImmune responsePrognostic powerTumor growthPatientsChemotherapyFactor receptorCancerFraction of cellsEstrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1% to 10% ER-Positive by Immunohistochemistry
Iwamoto T, Booser D, Valero V, Murray JL, Koenig K, Esteva FJ, Ueno NT, Zhang J, Shi W, Qi Y, Matsuoka J, Yang EJ, Hortobagyi GN, Hatzis C, Symmans WF, Pusztai L. Estrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1% to 10% ER-Positive by Immunohistochemistry. Journal Of Clinical Oncology 2012, 30: 729-734. PMID: 22291085, DOI: 10.1200/jco.2011.36.2574.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsEstrogen Receptor alphaFemaleGene ExpressionGene Expression ProfilingHumansImmunohistochemistryRandomized Controlled Trials as TopicRNA, MessengerConceptsER-positive patientsIHC-positive patientsER-positive cancersESR1 mRNA expressionGene signature scoreER statusBreast cancerSignature scoreEstrogen receptor-positive cancersMRNA expressionAdjuvant endocrine therapyEndocrine-sensitive tumorsER-negative cohortER-positive cohortER-negative groupER-positive tumorsOverall survival ratePrimary breast cancerER-negative cancersReceptor-positive cancersSafe clinical approachEstrogen receptor mRNAEndocrine therapyER-positiveAffymetrix U133A gene chips
2011
Consistent metagenes from cancer expression profiles yield agent specific predictors of chemotherapy response
Li Q, Eklund AC, Birkbak NJ, Desmedt C, Haibe-Kains B, Sotiriou C, Symmans WF, Pusztai L, Brunak S, Richardson AL, Szallasi Z. Consistent metagenes from cancer expression profiles yield agent specific predictors of chemotherapy response. BMC Bioinformatics 2011, 12: 310. PMID: 21798043, PMCID: PMC3155975, DOI: 10.1186/1471-2105-12-310.Peer-Reviewed Original ResearchConceptsEarly-stage lung cancerStage lung cancerNegative breast cancerCancer treatment decisionsHuman tumor samplesNeoadjuvant therapyChemotherapy responseLung cancerBreast cancerTreatment decisionsIndependent cohortPrognostic classifierAccurate biomarkersCancer expression profilesTumor typesPotential biomarkersTumor samplesConclusionsThese resultsSpecific predictorsStrong associationReliable predictorCohortCancerPredictorsBiomarkers
2010
Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer
Iwamoto T, Bianchini G, Qi Y, Cristofanilli M, Lucci A, Woodward WA, Reuben JM, Matsuoka J, Gong Y, Krishnamurthy S, Valero V, Hortobagyi GN, Robertson F, Symmans WF, Pusztai L, Ueno NT. Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer. Breast Cancer Research And Treatment 2010, 125: 785-795. PMID: 21153052, PMCID: PMC4109066, DOI: 10.1007/s10549-010-1280-6.Peer-Reviewed Original ResearchConceptsInflammatory breast cancerClinical subtypesBreast cancerNon-IBC patientsCase-control studyDistinct clinical subtypesDifferent molecular subtypesNon-IBC tumorsSignificant differencesNon-IBC specimensImmune system-related pathwaysLipid metabolism-related pathwaysHER2 statusReceptor phenotypeMetabolism-related pathwaysMolecular subtypesIBC tumorsSurvival curvesSubtypesTumor samplesHormone receptorsCancerPatientsT-testHER2Genomic Index of Sensitivity to Endocrine Therapy for Breast Cancer
Symmans WF, Hatzis C, Sotiriou C, Andre F, Peintinger F, Regitnig P, Daxenbichler G, Desmedt C, Domont J, Marth C, Delaloge S, Bauernhofer T, Valero V, Booser DJ, Hortobagyi GN, Pusztai L. Genomic Index of Sensitivity to Endocrine Therapy for Breast Cancer. Journal Of Clinical Oncology 2010, 28: 4111-4119. PMID: 20697068, PMCID: PMC2953969, DOI: 10.1200/jco.2010.28.4273.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalAromatase InhibitorsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantChi-Square DistributionDisease-Free SurvivalEstrogen Receptor alphaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenomicsHumansMiddle AgedNeoplasm StagingOligonucleotide Array Sequence AnalysisPatient SelectionProportional Hazards ModelsRisk AssessmentRisk FactorsSurvival AnalysisTamoxifenTime FactorsTranscription, GeneticTreatment OutcomeConceptsAdjuvant endocrine therapyEndocrine therapyBreast cancerDistant relapseER-positive breast cancerChemo-endocrine therapyDistant relapse riskYears of tamoxifenAdjuvant systemic therapyEstrogen receptor αBreast cancer samplesPrior chemotherapyNeoadjuvant chemotherapyPathologic responseSurvival benefitSystemic therapyUntreated cohortRelapse riskDeath riskTherapy indexAromatase inhibitionESR1 levelsReceptor αTamoxifenTherapyEstrogen Receptor Expression and Docetaxel Efficacy in Patients with Metastatic Breast Cancer: A Pooled Analysis of Four Randomized Trials
Andre F, Broglio K, Pusztai L, Berrada N, Mackey JR, Nabholtz JM, Chan S, Hortobagyi GN. Estrogen Receptor Expression and Docetaxel Efficacy in Patients with Metastatic Breast Cancer: A Pooled Analysis of Four Randomized Trials. The Oncologist 2010, 15: 476-483. PMID: 20421265, PMCID: PMC3227977, DOI: 10.1634/theoncologist.2009-0150.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerEfficacy of docetaxelBreast cancerHigh response rateER expressionResponse rateEstrogen receptorHazard ratioRandomized trialsDisease progressionProgression-free survival timeCox proportional hazards modelDocetaxel-based regimenEstrogen receptor expressionProportional hazards modelEffect of docetaxelER- diseasePFS timeDocetaxel efficacyPooled analysisTumor responseReceptor expressionSurvival timeLower riskHazards model
2009
Evaluation of Microtubule-Associated Protein-Tau Expression As a Prognostic and Predictive Marker in the NSABP-B 28 Randomized Clinical Trial
Pusztai L, Jeong JH, Gong Y, Ross JS, Kim C, Paik S, Rouzier R, Andre F, Hortobagyi GN, Wolmark N, Symmans WF. Evaluation of Microtubule-Associated Protein-Tau Expression As a Prognostic and Predictive Marker in the NSABP-B 28 Randomized Clinical Trial. Journal Of Clinical Oncology 2009, 27: 4287-4292. PMID: 19667268, PMCID: PMC2744271, DOI: 10.1200/jco.2008.21.6887.Peer-Reviewed Original ResearchMeSH KeywordsAnthracyclinesAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDoxorubicinEstrogen Receptor alphaFemaleFollow-Up StudiesHumansImmunohistochemistryKaplan-Meier EstimateMaleMicrotubule-Associated ProteinsMiddle AgedMultivariate AnalysisPaclitaxelPredictive Value of TestsPrognosisProportional Hazards ModelsRandomized Controlled Trials as TopicReceptor, ErbB-2Tau ProteinsConceptsDisease-free survivalOverall survivalTau protein expressionTau expressionEndocrine therapyPaclitaxel chemotherapyClinical trialsHuman epidermal growth factor receptor 2 (HER2) expressionEpidermal growth factor receptor 2 expressionBetter disease-free survivalWorse disease-free survivalD. Anderson Cancer CenterPrimary breast cancer specimensCourses of doxorubicinHER2-positive statusHormone receptor positiveNational Surgical BreastAdjuvant endocrine therapyPercent of patientsProtein expressionGreater tumor sizeER-positive statusEstrogen receptor-positive statusLow histologic gradeAnderson Cancer Center