2023
Evaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial
Speers C, Symmans W, Barlow W, Trevarton A, The S, Du L, Rae J, Shak S, Baehner R, Sharma P, Pusztai L, Hortobagyi G, Hayes D, Albain K, Godwin A, Thompson A. Evaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial. Journal Of Clinical Oncology 2023, 41: 1841-1848. PMID: 36649570, PMCID: PMC10082279, DOI: 10.1200/jco.22.01499.Peer-Reviewed Original ResearchConceptsBreast Recurrence ScoreAnthracycline-based chemotherapyDisease-free survivalRecurrence scoreEndocrine therapyTherapy indexAdjuvant anthracycline-based chemotherapyNode-positive breast cancerAdjuvant endocrine therapyPrimary end pointSubset of patientsPostmenopausal patientsChemotherapy benefitTreatment armsPrognostic indexPrognostic informationBreast cancerPrognostic assessmentPrognostic performancePatientsEnd pointTumor samplesChemotherapyClinical validationProportional hazards assumption
2018
Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR
Generali D, Corona SP, Pusztai L, Rouzier R, Allevi G, Aguggini S, Milani M, Strina C, Frati A. Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR. Journal Of Cancer Research And Clinical Oncology 2018, 144: 601-606. PMID: 29344722, DOI: 10.1007/s00432-017-2574-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnthracyclinesAntibiotics, AntineoplasticAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyFemaleHumansMiddle AgedNeoadjuvant TherapyPreoperative PeriodRetrospective StudiesTamoxifenTreatment OutcomeConceptsAnthracycline-based chemotherapyNeoadjuvant chemotherapyHormone receptor-positive breast cancer patientsHormone receptor positive BC patientsReceptor-positive breast cancer patientsHormone receptor-positive BCHormone receptor-positive patientsNeoadjuvant anthracycline-based chemotherapyPathological complete response ratePositive breast cancer patientsReceptor-positive patientsComplete response rateUse of chemotherapyLuminal B tumorsBreast cancer patientsPositive BC patientsCombination of tamoxifenCombination of chemotherapyAddition of tamoxifenSmall patient populationProbability of benefitCremona HospitalEndocrine therapyHormonal therapyNeoadjuvant treatment
2015
Prospective assessment of the decision-making impact of the Breast Cancer Index in recommending extended adjuvant endocrine therapy for patients with early-stage ER-positive breast cancer
Sanft T, Aktas B, Schroeder B, Bossuyt V, DiGiovanna M, Abu-Khalaf M, Chung G, Silber A, Hofstatter E, Mougalian S, Epstein L, Hatzis C, Schnabel C, Pusztai L. Prospective assessment of the decision-making impact of the Breast Cancer Index in recommending extended adjuvant endocrine therapy for patients with early-stage ER-positive breast cancer. Breast Cancer Research And Treatment 2015, 154: 533-541. PMID: 26578401, PMCID: PMC4661200, DOI: 10.1007/s10549-015-3631-9.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic Agents, HormonalAnxietyBreast NeoplasmsChemotherapy, AdjuvantDecision MakingFemaleGene Expression Regulation, NeoplasticGenetic TestingHumansMiddle AgedNeoplasm Recurrence, LocalPrognosisProspective StudiesReceptors, EstrogenSurveys and QuestionnairesTamoxifenConceptsBreast Cancer IndexExtended endocrine therapyER-positive breast cancerAdjuvant endocrine therapyEndocrine therapyDecisional Conflict ScaleBreast cancerCancer indexPhysician recommendationRisk/benefit discussionEarly-stage estrogen receptorEndocrine therapy trialsYale Cancer CenterPositive breast cancerState-Trait Anxiety Inventory FormMean STAIExtended therapyLate recurrenceAbsolute benefitCancer CenterPatient satisfactionPrognostic informationTreatment recommendationsPatient anxietyImproved outcomesGenomic predictor of residual risk of recurrence after adjuvant chemotherapy and endocrine therapy in high risk estrogen receptor-positive breast cancers
Khan SS, Karn T, Symmans WF, Rody A, Müller V, Holtrich U, Becker S, Pusztai L, Hatzis C. Genomic predictor of residual risk of recurrence after adjuvant chemotherapy and endocrine therapy in high risk estrogen receptor-positive breast cancers. Breast Cancer Research And Treatment 2015, 149: 789-797. PMID: 25651779, DOI: 10.1007/s10549-015-3277-7.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalAdjuvant chemotherapyEndocrine therapyHigh riskOncotype DXBreast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerRisk categoriesEarly-stage estrogen receptorEndocrine therapy sensitivityGood prognosis patientsER-positive patientsHigh-risk patientsPoor prognosis groupPositive breast cancerLow-risk groupAdjuvant endocrineMultimodality therapyPrognosis patientsRisk patientsEndocrine sensitivityIndependent predictorsPrognosis groupT stage
2013
Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers
Bianchini G, Pusztai L, Karn T, Iwamoto T, Rody A, Kelly C, Müller V, Schmidt M, Qi Y, Holtrich U, Becker S, Santarpia L, Fasolo A, Del Conte G, Zambetti M, Sotiriou C, Haibe-Kains B, Symmans WF, Gianni L. Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers. Breast Cancer Research 2013, 15: r86. PMID: 24060333, PMCID: PMC3978752, DOI: 10.1186/bcr3481.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, HormonalBiomarkers, TumorBreast NeoplasmsCell ProliferationChemoradiotherapy, AdjuvantEstrogensFemaleFollow-Up StudiesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedMitosisNeoplasm GradingNeoplasm MetastasisNeoplasm Recurrence, LocalNeoplasm StagingPrognosisReceptors, EstrogenRiskSignal TransductionTamoxifenConceptsNode-negative tumorsLate relapseNeoadjuvant letrozoleEndocrine therapyEarly relapseNegative tumorsBreast cancerEstrogen receptor-positive breast cancerProliferation markersReceptor-positive breast cancerER-positive breast cancerAdjuvant endocrine therapyAffymetrix gene expression profilesExtended endocrine therapyTamoxifen-treated patientsER-positive patientsGenomic grade indexPositive breast cancerRisk of recurrenceRisk of relapseEstrogen receptor activitySmall independent cohortEstrogen-related genesAdjuvant tamoxifenSystemic therapyConcordance Between CYP2D6 Genotypes Obtained From Tumor-Derived and Germline DNA
Rae JM, Regan MM, Thibert JN, Gersch C, Thomas D, Leyland-Jones B, Viale G, Pusztai L, Hayes DF, Skaar T, Van Poznak C. Concordance Between CYP2D6 Genotypes Obtained From Tumor-Derived and Germline DNA. Journal Of The National Cancer Institute 2013, 105: 1332-1334. PMID: 23958736, PMCID: PMC3888280, DOI: 10.1093/jnci/djt204.Peer-Reviewed Original ResearchConceptsCYP2D6 genotypeCYP2D6 metabolic phenotypeBreast cancer patientsMetabolic phenotypeAnti-estrogen tamoxifenCancer clinical trialsCancer patientsClinical trialsTumor alterationsGermline DNAConflicting resultsPatientsTumorsTissue sourcesGenotype association studiesConcordanceGenotypesPhenotypeAssociation studiesFFPETTamoxifenEndoxifenWBCCYP2D6TrialsA 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories
Szekely B, Iwamoto T, Szasz AM, Qi Y, Matsuoka J, Symmans WF, Tokes AM, Kulka J, Swanton C, Pusztai L. A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories. Breast Cancer Research And Treatment 2013, 138: 691-698. PMID: 23504136, DOI: 10.1007/s10549-013-2475-4.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmBreast NeoplasmsCell ProliferationChemotherapy, AdjuvantCohort StudiesDatabases, GeneticDNA Topoisomerases, Type IIDNA-Binding ProteinsFemaleForkhead Box Protein M1Forkhead Transcription FactorsGene Expression Regulation, NeoplasticGenome, HumanHumansKi-67 AntigenPoly-ADP-Ribose Binding ProteinsPredictive Value of TestsPrognosisReceptors, EstrogenSurvival RateTamoxifenConceptsGenomic grade indexGrade 2 cancersPrognostic valueProliferation scoreBreast cancerDistant metastasis-free survival curvesGrade 2Metastasis-free survival curvesER-positive breast cancerSystemic adjuvant therapyHigh expressionCohort of patientsHistological grade 2Intermediate-risk cancerPositive breast cancerSimilar prognostic valueGrade 2 tumorsHigh-risk groupGrade 1 cancersHistological grade groupsNon-significant trendWorse DMFSAdjuvant tamoxifenAdjuvant therapyWorse survival
2012
Centromere protein-A, an essential centromere protein, is a prognostic marker for relapse in estrogen receptor-positive breast cancer
McGovern SL, Qi Y, Pusztai L, Symmans WF, Buchholz TA. Centromere protein-A, an essential centromere protein, is a prognostic marker for relapse in estrogen receptor-positive breast cancer. Breast Cancer Research 2012, 14: r72. PMID: 22559056, PMCID: PMC3446334, DOI: 10.1186/bcr3181.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, HormonalAutoantigensBiomarkers, TumorBreast NeoplasmsCentromere Protein ACentromere Protein BChromosomal Proteins, Non-HistoneDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansKi-67 AntigenMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalReceptors, EstrogenRNA, MessengerTamoxifenConceptsER-positive diseaseDistant relapse-free survivalSystemic therapyER-negative tumorsIndependent prognostic markerNeoadjuvant chemotherapyPrognostic markerBreast cancerChemotherapy responseKi-67Estrogen receptor-positive breast cancerReceptor-positive breast cancerER-positive breast cancerSignificant independent prognostic markerER-positive tumorsRelapse-free survivalBreast cancer patientsHigh-grade cancerSignificant independent predictorsKi-67 expressionFree survivalHazard ratioIndependent predictorsPrognostic factorsNegative tumors
2011
Effect of CYP2D6 polymorphisms on breast cancer recurrence
Morrow PK, Serna R, Broglio K, Pusztai L, Nikoloff DM, Hillman GR, Fontecha M, Li R, Michaud L, Hortobagyi G, Gonzalez‐Angulo A. Effect of CYP2D6 polymorphisms on breast cancer recurrence. Cancer 2011, 118: 1221-1227. PMID: 21823108, DOI: 10.1002/cncr.26407.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinomaCase-Control StudiesCohort StudiesCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsEnzyme InhibitorsFemaleFollow-Up StudiesGenetic Predisposition to DiseaseHumansMastectomyMiddle AgedNeoplasm Recurrence, LocalPolymorphism, GeneticTamoxifenConceptsEarly breast cancerBreast cancer recurrenceAdjuvant tamoxifen therapyCancer recurrenceTamoxifen therapyMedical historyCYP2D6 genotypeTexas MD Anderson Cancer CenterFresh frozen tumor samplesCytochrome P450 2D6 polymorphismMD Anderson Cancer CenterBreast cancer patientsRisk of recurrenceCase-control studyAnderson Cancer CenterPatient's medical historyFrozen tumor samplesAdjuvant tamoxifenAdjuvant therapyConcomitant medicationsPatient characteristicsAmpliChip CYP450 TestCYP2D6 metabolismDisease recurrenceCancer Center
2010
Molecular Anatomy of Breast Cancer Stroma and Its Prognostic Value in Estrogen Receptor–Positive and –Negative Cancers
Bianchini G, Qi Y, Alvarez RH, Iwamoto T, Coutant C, Ibrahim NK, Valero V, Cristofanilli M, Green MC, Radvanyi L, Hatzis C, Hortobagyi GN, Andre F, Gianni L, Symmans WF, Pusztai L. Molecular Anatomy of Breast Cancer Stroma and Its Prognostic Value in Estrogen Receptor–Positive and –Negative Cancers. Journal Of Clinical Oncology 2010, 28: 4316-4323. PMID: 20805453, DOI: 10.1200/jco.2009.27.2419.Peer-Reviewed Original ResearchMeSH KeywordsAmyloid beta-Protein PrecursorAntineoplastic Agents, HormonalBiopsy, Fine-NeedleB-LymphocytesBreast NeoplasmsChi-Square DistributionCollagen Type IVExtracellular Matrix ProteinsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMetagenomeNeoplasm Recurrence, LocalPhospholipid Transfer ProteinsPrognosisProportional Hazards ModelsProspective StudiesProtease NexinsProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Cell SurfaceReceptors, EstrogenReceptors, Transforming Growth Factor betaSurvival AnalysisTamoxifenConceptsER-negative cancersBreast cancer stromaER-positive cancersPrognostic valueCancer stromaNegative cancersProliferative cancersSystemic adjuvant therapyTamoxifen-treated patientsNode-negative patientsEstrogen-receptor positiveStrong prognostic valueCore needle biopsySubset of tumorsLess prognostic valueDistant relapseAdjuvant therapyHazard ratioFavorable prognosisHighest tertilePrognostic scoreCore biopsyBreast cancerImmune functionMultivariate analysisGenomic 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 αTamoxifenTherapyPIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer
Loi S, Haibe-Kains B, Majjaj S, Lallemand F, Durbecq V, Larsimont D, Gonzalez-Angulo AM, Pusztai L, Symmans WF, Bardelli A, Ellis P, Tutt AN, Gillett CE, Hennessy BT, Mills GB, Phillips WA, Piccart MJ, Speed TP, McArthur GA, Sotiriou C. PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 10208-10213. PMID: 20479250, PMCID: PMC2890442, DOI: 10.1073/pnas.0907011107.Peer-Reviewed Original ResearchMeSH KeywordsAntibiotics, AntineoplasticAntineoplastic Agents, HormonalBase SequenceBreast NeoplasmsCell Line, TumorClass I Phosphatidylinositol 3-KinasesDNA PrimersFemaleGene Expression ProfilingHumansMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesMutationNeoplasms, Hormone-DependentOligonucleotide Array Sequence AnalysisPhosphatidylinositol 3-KinasesPrognosisProteinsProto-Oncogene Proteins c-aktReceptor, ErbB-2Receptors, EstrogenSignal TransductionSirolimusTamoxifenTOR Serine-Threonine KinasesTranscription FactorsConceptsBreast cancerPIK3CA mutationsClinical outcomesEstrogen receptor-positive breast cancerReceptor-positive breast cancerGene signaturePIK3CA mutation statusPI3K/mTOR inhibitorBetter clinical outcomesPI3K/mTOR inhibitionHuman breast cancerBC cell linesPIK3CA mutant breast cancersCommon genetic aberrationsTamoxifen monotherapyBetter prognosisMTOR inhibitorsBetter outcomesMutation statusMTOR inhibitionPathway activationExperimental modelGenetic aberrationsPrognosisCell lines
2008
Current Status of Prognostic Profiling in Breast Cancer
Pusztai L. Current Status of Prognostic Profiling in Breast Cancer. The Oncologist 2008, 13: 350-360. PMID: 18448548, DOI: 10.1634/theoncologist.2007-0216.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClinical Trials as TopicDNA Topoisomerases, Type IIDNA-Binding ProteinsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansOligonucleotide Array Sequence AnalysisOncogenesPredictive Value of TestsPrognosisReceptor, ErbB-2Receptors, EstrogenResearch DesignTamoxifenTaxoidsTreatment OutcomeConceptsBreast cancerClinical-pathological variablesClinical trial planningClinical courseClinical outcomesPathological variablesTreatment armsPrognostic informationClinical trialsTreatment strategiesClinicopathologic parametersHeterogeneous diseaseSpecific treatmentTherapeutic targetPrognostic profilingClinical heterogeneityGene expression fingerprintProspective tissue collectionAbnormal gene expressionIndividual tumorsPrognostic testTumorsPredictive indicatorIndividual diseasesTrial planning
2007
Microtubule-Associated Protein-tau is a Bifunctional Predictor of Endocrine Sensitivity and Chemotherapy Resistance in Estrogen Receptor–Positive Breast Cancer
Andre F, Hatzis C, Anderson K, Sotiriou C, Mazouni C, Mejia J, Wang B, Hortobagyi GN, Symmans WF, Pusztai L. Microtubule-Associated Protein-tau is a Bifunctional Predictor of Endocrine Sensitivity and Chemotherapy Resistance in Estrogen Receptor–Positive Breast Cancer. Clinical Cancer Research 2007, 13: 2061-2067. PMID: 17404087, DOI: 10.1158/1078-0432.ccr-06-2078.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDrug Resistance, NeoplasmEstrogen Receptor ModulatorsFemaleGene ExpressionGene Expression ProfilingHumansMiddle AgedNeoplasms, Hormone-DependentPrognosisReceptors, EstrogenRNA, MessengerTamoxifenTau ProteinsConceptsTau mRNA expressionBreast cancerPredictive valueTau expressionMRNA expressionEndocrine therapyEstrogen receptor-positive breast cancerPositive primary breast cancerReceptor-positive breast cancerER-positive breast cancerBorderline nonsignificant associationLow tau expressionPure prognostic valueSystemic adjuvant therapyTaxane-containing chemotherapyChemotherapy-resistant diseasePathologic complete responseER-positive cancersPrimary breast cancerDifferent outcome groupsWilcoxon rank sum testRank sum testAdjuvant tamoxifenPreoperative paclitaxelAdjuvant therapy