2022
Molecular differences between younger versus older ER-positive and HER2-negative breast cancers
Qing T, Karn T, Rozenblit M, Foldi J, Marczyk M, Shan N, Blenman K, Holtrich U, Kalinsky K, Meric-Bernstam F, Pusztai L. Molecular differences between younger versus older ER-positive and HER2-negative breast cancers. Npj Breast Cancer 2022, 8: 119. PMID: 36344517, PMCID: PMC9640562, DOI: 10.1038/s41523-022-00492-0.Peer-Reviewed Original ResearchBreast cancerYounger patientsHER2-negative breast cancerNode-positive breast cancerNode-negative diseaseSame clinical featuresHigh mutation burdenLower mRNA expressionAdjuvant chemotherapyMicroarray cohortTAILORx trialOvarian suppressionOlder patientsPatient ageClinical featuresProliferation-related gene expressionScore 0Mutation burdenCopy number gainsOlder womenGATA3 mutationsAge groupsGene signatureMRNA expressionChemotherapy
2019
The impact of RNA extraction method on accurate RNA sequencing from formalin-fixed paraffin-embedded tissues
Marczyk M, Fu C, Lau R, Du L, Trevarton AJ, Sinn BV, Gould RE, Pusztai L, Hatzis C, Symmans WF. The impact of RNA extraction method on accurate RNA sequencing from formalin-fixed paraffin-embedded tissues. BMC Cancer 2019, 19: 1189. PMID: 31805884, PMCID: PMC6896723, DOI: 10.1186/s12885-019-6363-0.Peer-Reviewed Original ResearchConceptsBreast cancerFresh frozenParaffin-embedded tumor samplesFF samplesFFPE samplesConcordance correlation coefficientMixed-effects model analysisBreast cancer signaturesQiagen RNeasy kitWhole transcriptome RNA sequencingParaffin-embedded tissuesTranscriptome RNA sequencingLinear mixed-effects model analysisGene expression signaturesDifferent kitsClinical trialsGene signatureTumor samplesGene expressionTranslational researchCancerTissue samplesExpression signaturesArchival formalinSimilar concordance
2018
Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial
Powles RL, Redmond D, Sotiriou C, Loi S, Fumagalli D, Nuciforo P, Harbeck N, de Azambuja E, Sarp S, Di Cosimo S, Huober J, Baselga J, Piccart-Gebhart M, Elemento O, Pusztai L, Hatzis C. Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncology 2018, 4: e181564-e181564. PMID: 29902299, PMCID: PMC6224305, DOI: 10.1001/jamaoncol.2018.1564.Peer-Reviewed Original ResearchConceptsDual HER2 blockadeImmune gene signaturesPathologic complete responseDual HER2HER2 blockadeNeoALTTO trialDual anti-HER2 blockadeHigher immune gene expressionTrastuzumab Treatment Optimisation (ALTTO) trialHER2-positive breast cancerGene signatureAnti-HER2 blockadeHigher useHER2-positive patientsMultivariable logistic regressionRandomized clinical trialsGood responseHigh rateImmune gene expressionNeoadjuvant lapatinibTherapy armIdentifies patientsNeoadjuvant therapyComplete responseGene expression signatures
2017
RNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy: A Secondary Analysis of the NeoALTTO Randomized Clinical Trial
Fumagalli D, Venet D, Ignatiadis M, Azim HA, Maetens M, Rothé F, Salgado R, Bradbury I, Pusztai L, Harbeck N, Gomez H, Chang TW, Coccia-Portugal MA, Di Cosimo S, de Azambuja E, de la Peña L, Nuciforo P, Brase JC, Huober J, Baselga J, Piccart M, Loi S, Sotiriou C. RNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy: A Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncology 2017, 3: 227-234. PMID: 27684533, PMCID: PMC5374044, DOI: 10.1001/jamaoncol.2016.3824.Peer-Reviewed Original ResearchEvent-free survivalAnti-HER2 therapyAnti-HER2 agentsErbB2/HER2Genomic grade indexCombination armTreatment armsGene signatureBreast cancerHER2-positive early-stage breast cancerNeoadjuvant anti-HER2 therapyPathologic complete response rateHuman epidermal growth factor receptor 2Early-stage breast cancerEpidermal growth factor receptor 2Candidate predictive markersCycles of fluorouracilDual HER2 blockadeImmune gene signaturesComplete response rateGrowth factor receptor 2Positive breast cancerLong-term outcomesRandomized clinical trialsHigh PCR
2014
Gene Signature–Guided Dasatinib Therapy in Metastatic Breast Cancer
Pusztai L, Moulder S, Altan M, Kwiatkowski D, Valero V, Ueno NT, Esteva FJ, Avritscher R, Qi Y, Strauss L, Hortobagyi GN, Hatzis C, Symmans WF. Gene Signature–Guided Dasatinib Therapy in Metastatic Breast Cancer. Clinical Cancer Research 2014, 20: 5265-5271. PMID: 25172932, DOI: 10.1158/1078-0432.ccr-14-0800.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerPredictive gene signaturesGene signatureClinical benefitBiopsy-related adverse eventsSingle-agent activityStable diseaseDasatinib therapyAdverse eventsUnderwent biopsyUnselected patientsPreclinical evidenceUnexpected toxicitiesThree-armPatientsSingle agentMolecular testingCLIA laboratoryDasatinib responseDasatinibBiopsyGene expression profilingCancerExpression profiling
2013
Correlation of intratumor gene expression heterogeneity with chemotherapy sensitivity in breast cancer.
Natowicz R, Jiang T, Shi W, Qi Y, Delpech Y, Symmans W, Pusztai L. Correlation of intratumor gene expression heterogeneity with chemotherapy sensitivity in breast cancer. Journal Of Clinical Oncology 2013, 31: 1013-1013. DOI: 10.1200/jco.2013.31.15_suppl.1013.Peer-Reviewed Original ResearchPathologic complete responseBasal-like cancersBreast cancerNeoadjuvant chemotherapyChemotherapy sensitivityCancer subtypesLuminal B cancersDifferent molecular subtypesBreast cancer subtypesB cancersComplete responseLuminal cancersResidual diseaseMolecular subtypesStage ICancerGene signatureGreat heterogeneitySubtypesTumor heterogeneityChemotherapySignificant differences
2011
Homogeneous Datasets of Triple Negative Breast Cancers Enable the Identification of Novel Prognostic and Predictive Signatures
Karn T, Pusztai L, Holtrich U, Iwamoto T, Shiang CY, Schmidt M, Müller V, Solbach C, Gaetje R, Hanker L, Ahr A, Liedtke C, Ruckhäberle E, Kaufmann M, Rody A. Homogeneous Datasets of Triple Negative Breast Cancers Enable the Identification of Novel Prognostic and Predictive Signatures. PLOS ONE 2011, 6: e28403. PMID: 22220191, PMCID: PMC3248403, DOI: 10.1371/journal.pone.0028403.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsCohort StudiesDatabases, GeneticFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansKaplan-Meier EstimateNeoadjuvant TherapyPredictive Value of TestsPrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneReproducibility of ResultsConceptsPrognostic signatureValidation cohortBreast cancerPredictive valueTriple-negative breast cancerEvent-free survivalTriple-negative cancersHigh-risk groupIndependent validation cohortNegative breast cancerModest predictive valuePrognostic gene signaturePrognostic gene setsTNBC cohortNeoadjuvant chemotherapyPrognostic predictorPoor prognosisRisk groupsMultivariate analysisPredictive signatureNovel prognosticGene signatureSmall sample sizeCohortCancerPD03-02: Prognostic and Predictive Predictors for Triple Negative Breast Cancer.
Karn T, Pusztai L, Ruckhäberle E, Liedtke C, Schmidt M, Müller V, Gätje R, Hanker L, Ahr A, Holtrich U, Rody A, Kaufmann M. PD03-02: Prognostic and Predictive Predictors for Triple Negative Breast Cancer. Cancer Research 2011, 71: pd03-02-pd03-02. DOI: 10.1158/0008-5472.sabcs11-pd03-02.Peer-Reviewed Original ResearchTriple-negative breast cancerNegative breast cancerPrognostic signatureBreast cancerResponse of TNBCER-positive cancersPrognostic gene signatureMolecular phenotypesTNBC cohortNeoadjuvant chemotherapyHazard ratioBetter prognosisPrognostic predictorTherapeutic optionsPoor prognosisIndependent cohortPredictive valuePrognostic gene expression profilesMultivariate analysisGene signatureCancer ResCohortCancerPrognosisROC analysis
2010
Use of standard markers and incorporation of molecular markers into breast cancer therapy
Kaufmann M, Pusztai L, Members T. Use of standard markers and incorporation of molecular markers into breast cancer therapy. Cancer 2010, 117: 1575-1582. PMID: 21472705, DOI: 10.1002/cncr.25660.Peer-Reviewed Original ResearchConceptsFuture clinical trialsClinical trialsBreast cancerRoutine pathological evaluationBreast cancer managementCancer Research GroupBreast cancer therapyRoutine clinical decisionImportant therapeutic targetPredictive gene signaturesPathological evaluationPatient selectionConsensus recommendationsCancer managementHeterogeneous diseaseTherapeutic targetPredictive valueBreast pathologyClinical decisionDifferent subtypesGene signatureGenomic profilingClinical levelNew molecular markersOutcome predictionPredicting prognosis of breast cancer with gene signatures: are we lost in a sea of data?
Iwamoto T, Pusztai L. Predicting prognosis of breast cancer with gene signatures: are we lost in a sea of data? Genome Medicine 2010, 2: 81. PMID: 21092148, PMCID: PMC3016623, DOI: 10.1186/gm202.Peer-Reviewed Original ResearchPIK3CA 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
2009
Metastatic gene signatures and emerging novel prognostic tests in the management of early stage breast cancer
Tordai A, Liedtke C, Pusztai L. Metastatic gene signatures and emerging novel prognostic tests in the management of early stage breast cancer. Clinical & Experimental Metastasis 2009, 26: 625-632. PMID: 19381845, DOI: 10.1007/s10585-009-9261-z.Peer-Reviewed Original ResearchConceptsMetastatic gene signatureGene expression studiesGene expression profilingDistinct neoplastic diseasesExpression profilingDNA microarraysExpression studiesGene expressionMRNA transcriptsGene signatureSingle experimentNovel diagnostic assaysTranscriptsDiagnostic assaysNovel prognostic testsMicroarrayProfilingExpression
2008
Evaluation of biological pathways involved in chemotherapy response in breast cancer
Tordai A, Wang J, Andre F, Liedtke C, Yan K, Sotiriou C, Hortobagyi GN, Symmans WF, Pusztai L. Evaluation of biological pathways involved in chemotherapy response in breast cancer. Breast Cancer Research 2008, 10: r37. PMID: 18445275, PMCID: PMC2397539, DOI: 10.1186/bcr2088.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDoxorubicinDrug Resistance, NeoplasmE2F3 Transcription FactorFemaleFluorouracilGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, p53HumansKi-67 AntigenLymphatic MetastasisMiddle AgedMutationNeoadjuvant TherapyNeoplasm StagingPaclitaxelReceptors, EstrogenSignal TransductionTreatment OutcomeConceptsER-positive breast cancerPathologic complete responseER-positive cancersER-negative cancersGenomic grade indexBreast cancerChemotherapy sensitivityGene signatureER-negative breast cancerProliferation signatureER-positive patientsPositive breast cancerExpression of ERPreoperative paclitaxelProliferation gene signatureCyclophosphamide chemotherapyComplete responseResidual cancerChemotherapy responsePCR groupKi67 expressionEstrogen receptorIntroductionOur goalCancerChemotherapy
2006
DNA arrays as predictors of efficacy of adjuvant/neoadjuvant chemotherapy in breast cancer patients: Current data and issues on study design
Andre F, Mazouni C, Hortobagyi GN, Pusztai L. DNA arrays as predictors of efficacy of adjuvant/neoadjuvant chemotherapy in breast cancer patients: Current data and issues on study design. Biochimica Et Biophysica Acta 2006, 1766: 197-204. PMID: 16962247, DOI: 10.1016/j.bbcan.2006.08.002.Peer-Reviewed Original ResearchConceptsStudy designPredictive biomarkersBreast cancer patientsPredictors of efficacyBreast cancer populationCase-control studySevere side effectsNeoadjuvant chemotherapyResistant patientsCancer patientsCancer populationBreast cancerSide effectsMolecular subclassesPredictive diagnostic toolGene signatureChemotherapyPatientsCancer pharmacogenomicsVariable benefitDiagnostic toolBiomarkersCurrent dataEfficacyPredictors