2023
Variable Landscape of PD-L1 Expression in Breast Carcinoma as Detected by the DAKO 22C3 Immunohistochemistry Assay
Danziger N, Sokol E, Graf R, Hiemenz M, Maule J, Parimi V, Palmieri C, Pusztai L, Ross J, Huang R. Variable Landscape of PD-L1 Expression in Breast Carcinoma as Detected by the DAKO 22C3 Immunohistochemistry Assay. The Oncologist 2023, 28: 319-326. PMID: 36866462, PMCID: PMC10078903, DOI: 10.1093/oncolo/oyad025.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungHumansImmunohistochemistryLung NeoplasmsTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNegative triple negative breast cancerTNBC tissue samplesPD-L1 positivityPD-L1Dako 22C3Breast cancerDeath ligand 1 (PD-L1) immunohistochemistry (IHC) assaysPD-L1 groupNon-TNBC patientsTissue samplesComprehensive genomic profilingBreast cancer subtypesFoundationOne CDxImmunotherapy efficacyMetastatic sitesTNBC casesBC patientsBreast carcinomaPositive statusImmunohistochemistry assaysOptimum cutoffCancer subtypesGenomic profiling
2022
Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue
Fernandez AI, Liu M, Bellizzi A, Brock J, Fadare O, Hanley K, Harigopal M, Jorns JM, Kuba MG, Ly A, Podoll M, Rabe K, Sanders MA, Singh K, Snir OL, Soong TR, Wei S, Wen H, Wong S, Yoon E, Pusztai L, Reisenbichler E, Rimm DL. Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. JAMA Oncology 2022, 8: 1-4. PMID: 35113160, PMCID: PMC8814969, DOI: 10.1001/jamaoncol.2021.7239.Peer-Reviewed Original ResearchMeSH KeywordsBreastBreast NeoplasmsFemaleHumansImmunohistochemistryIn Situ Hybridization, FluorescenceReceptor, ErbB-2ConceptsBreast cancer biopsiesT-DXdCancer biopsiesLarge randomized clinical trialsRandomized clinical trialsERBB2 protein expressionCentral pathology laboratoryBreast cancer tissuesAmerican Pathologists surveysStudy of concordanceTrastuzumab deruxtecanERBB2 positivityPatient populationClinical trialsScore 0Breast cancerImmunohistochemistry scoreCancer tissuesIHC assaysPatientsPathology laboratoryProtein expressionBiopsyIHCConcordance
2021
Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer
Moutafi MK, Tao W, Huang R, Haberberger J, Alexander B, Ramkissoon S, Ross JS, Syrigos K, Wei W, Pusztai L, Rimm DL, Vathiotis IA. Comparison of programmed death-ligand 1 protein expression between primary and metastatic lesions in patients with lung cancer. Journal For ImmunoTherapy Of Cancer 2021, 9: e002230. PMID: 33833050, PMCID: PMC8039214, DOI: 10.1136/jitc-2020-002230.Peer-Reviewed Original ResearchConceptsPD-L1 expressionMetastatic lesionsLung cancer casesLung cancerCancer casesAdvanced stage non-small cell lung cancerNon-small cell lung cancerNon-squamous histologyCell lung cancerFuture patient managementDefinite diagnostic testSquamous histologyFoundation MedicineLymph nodesRoutine careHistologic subtypeMetastatic sitesPrimary lesionRetrospective studyAdrenal glandPrimary tumorPleural fluidPatient managementTrial designDrug Administration
2020
Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer
Huang RSP, Li X, Haberberger J, Sokol E, Severson E, Duncan DL, Hemmerich A, Edgerly C, Williams E, Elvin J, Vergilio J, Killian J, Lin D, Hiemenz M, Xiao J, McEwan D, Holmes O, Danziger N, Erlich R, Frampton G, Cohen M, McGregor K, Reddy P, Cardeiro D, Anhorn R, Venstrom J, Alexander B, Brown C, Pusztai L, Ross J, Ramkissoon S. Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer. The Oncologist 2020, 25: 943-953. PMID: 32869930, PMCID: PMC7648336, DOI: 10.1634/theoncologist.2020-0449.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorGenomicsHumansImmunohistochemistryTriple Negative Breast NeoplasmsConceptsComprehensive genomic profilingPD-L1 immunohistochemistryPotential therapeutic optionBreast cancerPD-L1Therapeutic optionsTriple negative breast cancer cohortDrug AdministrationHormone receptor-positive breast cancerReceptor-positive breast cancerGenomic profilingTriple-negative breast cancerPD-L1 positivityRoutine clinical careMutations/MbBreast cancer cohortBiomarker landscapeTNBC cohortNab-paclitaxelGermline testingConsecutive patientsReceptor negativeHER2-positiveClinical trialsPIK3CA mutationsProspective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer
Reisenbichler ES, Han G, Bellizzi A, Bossuyt V, Brock J, Cole K, Fadare O, Hameed O, Hanley K, Harrison BT, Kuba MG, Ly A, Miller D, Podoll M, Roden AC, Singh K, Sanders MA, Wei S, Wen H, Pelekanou V, Yaghoobi V, Ahmed F, Pusztai L, Rimm DL. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer. Modern Pathology 2020, 33: 1746-1752. PMID: 32300181, PMCID: PMC8366569, DOI: 10.1038/s41379-020-0544-x.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNegative breast cancerOverall percent agreementPD-L1Intraclass correlation coefficientBreast cancerAdvanced triple-negative breast cancerPD-L1 positive casesImmune cell stainingMultiple pathologistsPD-L1 scoringMulti-institutional evaluationLung cancer studiesAtezolizumab therapySP142 assaySP263 assaysPatient selectionSP263SP142US FoodDrug AdministrationPathologist's assessmentPositive casesReal-world settingPercent agreement
2019
Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, Roden AC, Hirsch FR, Wistuba II, Pusztai L. Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer. Breast Cancer Research 2019, 21: 72. PMID: 31196152, PMCID: PMC6567382, DOI: 10.1186/s13058-019-1156-6.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleHumansImmunohistochemistryPrognosisTriple Negative Breast NeoplasmsConceptsPD-L1 expressionImmune cell PD-L1 expressionLung cancerImmune cellsTriple-negative breast cancerEasy scoring methodCompanion diagnostic testsPD-L1Immune therapyBreast cancerImmunohistochemical testsBetter outcomesLarger studyTumor cellsDiagnostic testsCancerExpression findingsCellsExpressionPoor agreementScoring methodTherapyTrials
2018
Tumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial
Pelekanou V, Barlow WE, Nahleh Z, Wasserman B, Lo YC, von Wahlde MK, Hayes D, Hortobagyi GN, Gralow J, Tripathy D, Porter P, Szekely B, Hatzis C, Rimm DL, Pusztai L. Tumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial. Molecular Cancer Therapeutics 2018, 17: molcanther.1005.2017. PMID: 29588392, PMCID: PMC6548451, DOI: 10.1158/1535-7163.mct-17-1005.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPathologic complete responseTIL countPosttreatment tissuePD-L1Estrogen receptorImmune checkpoint inhibitor therapyPD-L1 positivity rateTumor-infiltrating lymphocyte countsDoxorubicin/cyclophosphamideCheckpoint inhibitor therapyPD-L1 levelsMol Cancer TherNab-paclitaxelLymphocyte countResidual cancerComplete responseER statusImmune changesInhibitor therapyCox regressionPatient populationControl armClinical trialsPositivity rate
2015
Multigene prognostic tests in breast cancer: past, present, future
Győrffy B, Hatzis C, Sanft T, Hofstatter E, Aktas B, Pusztai L. Multigene prognostic tests in breast cancer: past, present, future. Breast Cancer Research 2015, 17: 11. PMID: 25848861, PMCID: PMC4307898, DOI: 10.1186/s13058-015-0514-2.BooksConceptsER-negative cancersPrognostic valuePredictive markerBreast cancerPrognostic signatureExtended adjuvant endocrine therapyPrognostic testAdjuvant endocrine therapyCandidate predictive markersImmune gene signaturesPositive breast cancerGood prognostic valueSignificant prognostic valueTreatment response predictorsNew predictive markers
2013
Influence of genomics on adjuvant treatments for pre-invasive and invasive breast cancer
Abu-Khalaf M, Pusztai L. Influence of genomics on adjuvant treatments for pre-invasive and invasive breast cancer. The Breast 2013, 22: s83-s87. PMID: 24074799, DOI: 10.1016/j.breast.2013.07.015.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAntineoplastic Agents, HormonalBiopsy, NeedleBreast NeoplasmsChemotherapy, AdjuvantCost SavingsCost-Benefit AnalysisFemaleForecastingGenetic TestingGenomicsHumansImmunohistochemistryMiddle AgedNeoplasm InvasivenessNeoplasm StagingPrognosisReceptors, EstrogenRisk AssessmentSurvival AnalysisTreatment OutcomeConceptsLow-risk patientsBreast cancerRisk patientsTreatment recommendationsEarly-stage breast cancerER-positive breast cancerUse of chemotherapyInvasive breast cancerGenomic testingStage breast cancerInternational practice guidelinesMultivariate prognostic modelCost-effectiveness studiesPotential clinical valueAdjuvant treatmentBreast cancer biomarkersCurrent guidelinesPractice guidelinesClinical utilityClinical valueTumor markersStage IPrognostic modelPrognostic testClinical useInk4a/Arf−/− and HRAS(G12V) transform mouse mammary cells into triple-negative breast cancer containing tumorigenic CD49f− quiescent cells
Kai K, Iwamoto T, Kobayashi T, Arima Y, Takamoto Y, Ohnishi N, Bartholomeusz C, Horii R, Akiyama F, Hortobagyi GN, Pusztai L, Saya H, Ueno NT. Ink4a/Arf−/− and HRAS(G12V) transform mouse mammary cells into triple-negative breast cancer containing tumorigenic CD49f− quiescent cells. Oncogene 2013, 33: 440-448. PMID: 23376849, PMCID: PMC3957346, DOI: 10.1038/onc.2012.609.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Transformation, NeoplasticCyclin-Dependent Kinase Inhibitor p16FemaleFlow CytometryImmunohistochemistryIntegrin alpha6Mammary Neoplasms, ExperimentalMiceMice, Inbred C57BLMice, KnockoutNeoplastic Stem CellsOligonucleotide Array Sequence AnalysisProto-Oncogene Proteins p21(ras)Real-Time Polymerase Chain ReactionTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerHuman triple-negative breast cancerBreast cancerTumor-initiating potentialIntratumoral heterogeneityInk4a/Claudin-low breast cancerMouse mammary tumor modelNon-mammary tumorsHigh tumor-initiating potentialMouse mammary fat padMammary cellsMammary fat padMammary tumor modelIndividual breast tumorsTumor precursor cellsQuiescent cellsTumor-initiating cellsPathological featuresProgesterone receptorMammary tumorsEstrogen receptorAnimal modelsFat padBreast tumors
2012
Estrogen 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 ResearchConceptsER-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
Artificial neural network analysis of circulating tumor cells in metastatic breast cancer patients
Giordano A, Giuliano M, De Laurentiis M, Eleuteri A, Iorio F, Tagliaferri R, Hortobagyi GN, Pusztai L, De Placido S, Hess K, Cristofanilli M, Reuben JM. Artificial neural network analysis of circulating tumor cells in metastatic breast cancer patients. Breast Cancer Research And Treatment 2011, 129: 451-458. PMID: 21710134, DOI: 10.1007/s10549-011-1645-5.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsFemaleHumansImmunohistochemistryKaplan-Meier EstimateLinear ModelsMiddle AgedNeoplastic Cells, CirculatingNeural Networks, ComputerPrognosisProportional Hazards ModelsReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRetrospective StudiesRisk AssessmentRisk FactorsSurvival RateTexasTime FactorsConceptsMetastatic breast cancer patientsRisk of deathBreast cancer patientsCTC countMBC patientsPrognostic effectCancer patientsTumor subtypesTumor cellsMD Anderson Cancer CenterConsecutive MBC patientsTriple-negative MBCMetastatic disease sitesAnderson Cancer CenterTumor molecular subtypeNumber of CTCsMolecular tumor subtypesVisceral metastasesOverall survivalCancer CenterHER2 statusProgesterone receptorMolecular subtypesTherapy typePrognostic tool
2010
Molecular profiling contributes more than routine histology and immonohistochemistry to breast cancer diagnostics
Shiang C, Pusztai L. Molecular profiling contributes more than routine histology and immonohistochemistry to breast cancer diagnostics. Breast Cancer Research 2010, 12: s6. PMID: 21172090, PMCID: PMC3005726, DOI: 10.1186/bcr2735.Peer-Reviewed Original ResearchBreast cancer prognostic markers in the post-genomic era
Pusztai L, Iwamoto T. Breast cancer prognostic markers in the post-genomic era. Breast Cancer Research And Treatment 2010, 125: 647-650. PMID: 20464478, DOI: 10.1007/s10549-010-0932-x.Peer-Reviewed Original Research
2009
CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence
Andre F, Xia W, Conforti R, Wei Y, Boulet T, Tomasic G, Spielmann M, Zoubir M, Berrada N, Arriagada R, Hortobagyi GN, Hung M, Pusztai L, Delaloge S, Michiels S, Cristofanilli M. CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence. The Oncologist 2009, 14: 1182-1188. PMID: 19939894, DOI: 10.1634/theoncologist.2009-0161.Peer-Reviewed Original ResearchConceptsPrimary breast tumorsCXCR4 expressionBone metastasesBreast tumorsClinical characteristicsDistant metastasisPrognostic valueHigh riskLigand stromal cell-derived factor-1Stromal cell-derived factor-1Cell-derived factor-1Bone-targeted agentsEarly breast cancerProspective clinical trialsCox regression modelNovel adjuvant strategyExpression of CXCR4Chemokine receptor 4Early metastatic processOccurrence of metastasesSpecific organ sitesCXCR4 tumorsDistant recurrenceOverall survivalAdjuvant strategiesInhibition of Lipocalin 2 Impairs Breast Tumorigenesis and Metastasis
Leng X, Ding T, Lin H, Wang Y, Hu L, Hu J, Feig B, Zhang W, Pusztai L, Symmans WF, Wu Y, Arlinghaus RB. Inhibition of Lipocalin 2 Impairs Breast Tumorigenesis and Metastasis. Cancer Research 2009, 69: 8579-8584. PMID: 19887608, DOI: 10.1158/0008-5472.can-09-1934.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsBlotting, WesternBreast NeoplasmsCell Line, TumorFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunohistochemistryLipocalin-2LipocalinsMatrix Metalloproteinase 9MiceMice, KnockoutNeoplasm InvasivenessNF-kappa BOncogene ProteinsReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsLCN2 expressionBreast cancerBreast tumorigenesisMatrix metalloproteinase-9 activityTumor formationMammary tumor mouse modelMammary tumor formationMetalloproteinase-9 activityMatrix metalloproteinase-9Breast cancer therapyTumor mouse modelBreast tumor formationAkt/NFBreast cancer cellsMurine breast tumorsInhibitory monoclonal antibodiesLCN2 functionsLung metastasesLipocalin-2Metalloproteinase-9Mouse modelAggressive typeBreast tumorsKappaB pathwayMetastasisEvaluation 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 CenterPrognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer
Liedtke C, Broglio K, Moulder S, Hsu L, Kau S, Symmans WF, Albarracin C, Meric-Bernstam F, Woodward W, Theriault RL, Kiesel L, Hortobagyi GN, Pusztai L, Gonzalez-Angulo AM. Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Annals Of Oncology 2009, 20: 1953-1958. PMID: 19596702, PMCID: PMC2791352, DOI: 10.1093/annonc/mdp263.Peer-Reviewed Original ResearchConceptsTriple receptor-negative breast cancerRecurrent breast cancerPost-recurrence survivalProgesterone receptorRecurrent tumorsBreast cancerEstrogen receptorDiscordant casesBetter post-recurrence survivalReceptor-positive breast cancerReceptor-negative breast cancerDiscordant receptor statusHormone receptor measurementsPrognostic impactReceptor statusUnfavorable survivalPathological parametersHER2 statusPoor survivalReceptor measurementsIHC scorePatientsClinical phenotypeSuboptimal reproducibilityCancerThe HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine
Ross JS, Slodkowska EA, Symmans WF, Pusztai L, Ravdin PM, Hortobagyi GN. The HER-2 Receptor and Breast Cancer: Ten Years of Targeted Anti–HER-2 Therapy and Personalized Medicine. The Oncologist 2009, 14: 320-368. PMID: 19346299, DOI: 10.1634/theoncologist.2008-0230.Peer-Reviewed Original ResearchMeSH KeywordsAnthracyclinesAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBiomarkers, TumorBreast NeoplasmsEverolimusEvidence-Based MedicineFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryIn Situ HybridizationLapatinibNeoplasm StagingPolymerase Chain ReactionPractice Guidelines as TopicPrognosisPyrazolesPyrimidinesQuinazolinesReceptor, ErbB-2RNA, MessengerSirolimusSurvival AnalysisTaxoidsTrastuzumabTreatment OutcomeUp-RegulationConceptsBreast cancerOverall survivalInsulin-like growth factor receptor pathwayClinical Oncology-CollegeMetastatic breast cancerInvasive breast cancerAmerican Pathologists guidelinesHER-2 receptorTyrosine kinase inhibitorsTarget of therapyGrowth factor receptor pathwayKinase inhibitor lapatinibMean relative riskReal-time polymerase chain reactionTransmembrane tyrosine kinase receptorPrediction of responseChromosome 17 polysomyHormonal therapyTyrosine kinase receptorsTherapy toxicitySitu hybridizationPrognostic significancePolymerase chain reactionPathologists guidelinesRelative risk
2007
Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer
Andre F, Nahta R, Conforti R, Boulet T, Aziz M, Yuan LX, Meslin F, Spielmann M, Tomasic G, Pusztai L, Hortobagyi GN, Michiels S, Delaloge S, Esteva FJ. Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer. Annals Of Oncology 2007, 19: 315-320. PMID: 17804473, DOI: 10.1093/annonc/mdm429.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedBiomarkers, TumorBreast NeoplasmsChi-Square DistributionCohort StudiesCombined Modality TherapyDisease-Free SurvivalErbB ReceptorsFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansImmunohistochemistryMiddle AgedNeoplasm StagingPredictive Value of TestsProbabilityProportional Hazards ModelsProto-Oncogene Proteins c-aktRandomized Controlled Trials as TopicReceptor, ErbB-2Risk AssessmentSurvival AnalysisTime FactorsTreatment OutcomeConceptsEarly breast cancerBreast cancerPredictive valuePhosphorylated AktAdjuvant chemotherapyPAkt expressionAnthracycline-based adjuvant chemotherapyEarly-stage breast cancerEpidermal growth factor receptor expressionGrowth factor receptor expressionAkt phosphorylationBreast cancer tissuesFactor receptor expressionGrowth factor receptorHER2 tumorsRandomized trialsAssessable tumorsHER2 expressionReceptor expressionPositive stainingCancer tissuesEGFR expressionHER2Tumor resistancePatients