2020
Gene Expression Profiling as an Emerging Diagnostic Tool to Personalize Chemotherapy Selection for Early Stage Breast Cancer
Liedtke C, Pusztai L. Gene Expression Profiling as an Emerging Diagnostic Tool to Personalize Chemotherapy Selection for Early Stage Breast Cancer. 2020, 77-96. DOI: 10.1201/9780429137723-6.Peer-Reviewed Original ResearchBreast cancerEarly-stage breast cancerCombination chemotherapy regimensSubstantial tumor responseAdvanced breast cancerNeoadjuvant chemotherapy regimenStage breast cancerAdjuvant chemotherapyChemotherapy regimenNeoadjuvant therapyChemotherapy regimensPreoperative chemotherapyChemotherapy selectionOverall survivalInoperable cancerTumor responseStage ICancer tissuesCancerGene expression profilingChemotherapyDiagnostic toolCurrent standardSemiquantitative mannerExpression profiling
2013
Novel Functional Assay for Spindle-Assembly Checkpoint by Cyclin-Dependent Kinase Activity to Predict Taxane Chemosensitivity in Breast Tumor Patient
Torikoshi Y, Gohda K, Davis ML, Symmans WF, Pusztai L, Kazansky A, Nakayama S, Yoshida T, Matsushima T, Hortobagyi GN, Ishihara H, Kim SJ, Noguchi S, Ueno NT. Novel Functional Assay for Spindle-Assembly Checkpoint by Cyclin-Dependent Kinase Activity to Predict Taxane Chemosensitivity in Breast Tumor Patient. Journal Of Cancer 2013, 4: 697-702. PMID: 24312139, PMCID: PMC3842438, DOI: 10.7150/jca.6248.Peer-Reviewed Original ResearchTaxane-containing chemotherapyClinical responsePreoperative chemotherapyTaxane-induced cell deathAnthracycline-based treatmentFine-needle aspiration biopsyLarge prospective studiesBreast cancer patientsCyclin-dependent kinase 1Taxane-resistant tumorsLogistic regression analysisTaxane-containing therapyBreast tumor patientsDysfunction groupTaxane therapyPathologic responseProspective studyCancer patientsPredictive biomarkersTumor patientsBreast cancerClinicopathologic parametersAspiration biopsyBiopsy samplesPatients
2011
First generation prognostic gene signatures for breast cancer predict both survival and chemotherapy sensitivity and identify overlapping patient populations
Iwamoto T, Lee JS, Bianchini G, Hubbard RE, Young E, Matsuoka J, Kim SB, Symmans WF, Hortobagyi GN, Pusztai L. First generation prognostic gene signatures for breast cancer predict both survival and chemotherapy sensitivity and identify overlapping patient populations. Breast Cancer Research And Treatment 2011, 130: 155. PMID: 21833625, DOI: 10.1007/s10549-011-1706-9.Peer-Reviewed Original ResearchConceptsLong-term survivalPrognostic gene signatureClinical variablesChemotherapy responseGenomic prognostic markersPrognostic markerPredictive valueKaplan-Meir survival curvesSignificant independent predictive valuePathologic complete responseProgression-free survivalLong-term followIndependent predictive valueSame patient cohortReceiver operator characteristic curveOperator characteristic curveOverall survivalPreoperative chemotherapyComplete responseNodal statusIndependent prognosticClinicopathological variablesPatient populationHER2 statusPatient cohortA Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer
Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, Vidaurre T, Holmes F, Souchon E, Wang H, Martin M, Cotrina J, Gomez H, Hubbard R, Chacón JI, Ferrer-Lozano J, Dyer R, Buxton M, Gong Y, Wu Y, Ibrahim N, Andreopoulou E, Ueno NT, Hunt K, Yang W, Nazario A, DeMichele A, O’Shaughnessy J, Hortobagyi GN, Symmans WF. A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer. JAMA 2011, 305: 1873-1881. PMID: 21558518, PMCID: PMC5638042, DOI: 10.1001/jama.2011.593.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlgorithmsAnthracyclinesAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiopsy, NeedleBreast NeoplasmsBridged-Ring CompoundsDisease-Free SurvivalDrug Resistance, NeoplasmFemaleForecastingGene Expression ProfilingGenes, erbB-2Genes, NeoplasmGenomicsHumansMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalOligonucleotide Array Sequence AnalysisPredictive Value of TestsPrognosisProspective StudiesReceptors, EstrogenRiskTaxoidsConceptsDistant relapse-free survivalInvasive breast cancerBreast cancerGenomic predictorsD. Anderson Cancer CenterAnthracycline-based regimensER-negative subsetExcellent pathologic responseProspective multicenter studyRelapse-free survivalAbsolute risk reductionStandard cancer treatmentPredictors of responseIndependent validation cohortAnderson Cancer CenterNegative breast cancerCancer treatment strategiesSequential taxaneNeoadjuvant chemotherapyPreoperative chemotherapyPathologic responseWorse survivalEndocrine sensitivityER statusMulticenter study
2010
Gene Pathways Associated With Prognosis and Chemotherapy Sensitivity in Molecular Subtypes of Breast Cancer
Iwamoto T, Bianchini G, Booser D, Qi Y, Coutant C, Shiang CY, Santarpia L, Matsuoka J, Hortobagyi GN, Symmans WF, Holmes FA, O’Shaughnessy J, Hellerstedt B, Pippen J, Andre F, Simon R, Pusztai L. Gene Pathways Associated With Prognosis and Chemotherapy Sensitivity in Molecular Subtypes of Breast Cancer. Journal Of The National Cancer Institute 2010, 103: 264-272. PMID: 21191116, DOI: 10.1093/jnci/djq524.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantConfounding Factors, EpidemiologicCytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemDatabases, GeneticDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGTP-Binding ProteinsHumansMiddle AgedNeoadjuvant TherapyNeoplasm StagingPredictive Value of TestsPrognosisReceptors, EstrogenSignal TransductionTreatment OutcomeConceptsER-negative breast cancerPathological complete responseER-positive cancersER-negative cancersBreast cancerChemotherapy responseComplete responseBetter prognosisChemotherapy sensitivityLymph node-negative breast cancerNode-negative breast cancerSystemic adjuvant therapyCell cycle-related gene setsBreast cancer subtypesIngenuity Pathway AnalysisAdjuvant therapyPreoperative chemotherapyPoor prognosisPooled analysisEstrogen receptorTreatment responseMolecular subtypesAdditional cohortPrognosisStage IEvaluation of a 30-Gene Paclitaxel, Fluorouracil, Doxorubicin, and Cyclophosphamide Chemotherapy Response Predictor in a Multicenter Randomized Trial in Breast Cancer
Tabchy A, Valero V, Vidaurre T, Lluch A, Gomez H, Martin M, Qi Y, Barajas-Figueroa LJ, Souchon E, Coutant C, Doimi FD, Ibrahim NK, Gong Y, Hortobagyi GN, Hess KR, Symmans WF, Pusztai L. Evaluation of a 30-Gene Paclitaxel, Fluorouracil, Doxorubicin, and Cyclophosphamide Chemotherapy Response Predictor in a Multicenter Randomized Trial in Breast Cancer. Clinical Cancer Research 2010, 16: 5351-5361. PMID: 20829329, PMCID: PMC4181852, DOI: 10.1158/1078-0432.ccr-10-1265.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, PharmacologicalBiomarkers, TumorBreast NeoplasmsCarcinoma, Ductal, BreastCyclophosphamideDoxorubicinFemaleFluorouracilGene Expression Regulation, NeoplasticHumansMiddle AgedPaclitaxelPredictive Value of TestsPrognosisTreatment OutcomeConceptsPositive predictive valuePathologic complete responseFAC armPCR rateBreast cancerPredictive valueGene expression profilingDifferent molecular subsetsFine-needle aspiration biopsyMulticenter Randomized TrialInternational clinical trialsGenomic predictorsNegative predictive valueTreatment response predictionWeekly paclitaxelNeoadjuvant chemotherapyCyclophosphamide chemotherapyFAC chemotherapyPreoperative chemotherapyComplete responseRandomized trialsTreatment armsPredictive markerClinical trialsMolecular subsetsEvaluation of changes in serum protein profiles during neoadjuvant chemotherapy in HER2‐positive breast cancer using an LC‐MALDI‐TOF/MS procedure
Mazouni C, Baggerly K, Hawke D, Tsavachidis S, André F, Buzdar AU, Martin P, Kobayashi R, Pusztai L. Evaluation of changes in serum protein profiles during neoadjuvant chemotherapy in HER2‐positive breast cancer using an LC‐MALDI‐TOF/MS procedure. Proteomics 2010, 10: 3525-3532. PMID: 20827732, DOI: 10.1002/pmic.201000057.Peer-Reviewed Original ResearchConceptsPreoperative chemotherapyBreast cancerHemopexin precursorHER2-positive breast cancerApolipoprotein APost-chemotherapy samplesPre-chemotherapy samplesPathological complete responseBreast cancer patientsNon-responding groupSerum amyloid PSerum protein levelsSerum protein profilesNeoadjuvant chemotherapyComplete responseResidual diseaseResponder groupCancer patientsTumor responseComplement 3Tumor markersAmyloid PChemotherapyPatientsProtein profiles
2009
The Molecular Anatomy of Breast Cancer Stroma; Independent Prognostic Role in ER-Positive and ER-Negative Cancers.
Bianchini G, Bianchini G, Alvarez R, Qi Y, Hatzis C, Iwamoto T, Shiang C, Coutant C, Hortobagyi G, Symmans W, Pusztai L. The Molecular Anatomy of Breast Cancer Stroma; Independent Prognostic Role in ER-Positive and ER-Negative Cancers. Cancer Research 2009, 69: 105-105. DOI: 10.1158/0008-5472.sabcs-09-105.Peer-Reviewed Original ResearchDistant metastasis-free survivalCore needle biopsyFine-needle aspirationER- cancersPrognostic valueCancer cell linesER- tumorsB cells/plasma cellsStromal signaturesStromal genesBreast cancer stromaConsistent prognostic valueER- breast cancer cell linesReproducible prognostic markerTamoxifen-treated patientsIndependent prognostic roleER-negative cancersMetastasis-free survivalStromal gene signatureBreast cancer cell linesVariable prognostic valueCell linesFree survivalPreoperative chemotherapyUntreated patientsEvaluation of Changes in Plasma Protein Profiles during Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer Using MALDI-TOF/MS Procedure.
Mazouni C, Baggerly K, Hawke D, Tsavachidis S, André F, Buzdar A, Martin P, Kobayashi R, Pusztai L. Evaluation of Changes in Plasma Protein Profiles during Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer Using MALDI-TOF/MS Procedure. Cancer Research 2009, 69: 2037-2037. DOI: 10.1158/0008-5472.sabcs-09-2037.Peer-Reviewed Original ResearchNeoadjuvant chemotherapyHER2-positive breast cancerResponse groupPre-surgery samplesPathological complete responseBreast cancer patientsRandomized clinical trialsPreoperative chemotherapyComplete responsePlasma protein profileResidual diseaseCancer patientsTumor responseClinical trialsBreast cancerTumor markersChemotherapySerum profileBaseline samplesCancer ResPatientsRD groupEvaluation of changesP componentProtein profilesDirect comparison of logistic regression and recursive partitioning to predict chemotherapy response of breast cancer based on clinical pathological variables
Rouzier R, Coutant C, Lesieur B, Mazouni C, Incitti R, Natowicz R, Pusztai L. Direct comparison of logistic regression and recursive partitioning to predict chemotherapy response of breast cancer based on clinical pathological variables. Breast Cancer Research And Treatment 2009, 117: 325-331. PMID: 19152025, DOI: 10.1007/s10549-009-0308-2.Peer-Reviewed Original Research
2008
Collagen IV levels are elevated in the serum of patients with primary breast cancer compared to healthy volunteers
Mazouni C, Arun B, André F, Ayers M, Krishnamurthy S, Wang B, Hortobagyi GN, Buzdar AU, Pusztai L. Collagen IV levels are elevated in the serum of patients with primary breast cancer compared to healthy volunteers. British Journal Of Cancer 2008, 99: 68-71. PMID: 18560403, PMCID: PMC2453019, DOI: 10.1038/sj.bjc.6604443.Peer-Reviewed Original ResearchConceptsCollagen IV levelsHealthy womenCancer patientsBreast cancerPreoperative chemotherapySerum levelsCollagen IVBaseline serum levelsSerum collagen IVPrimary breast cancerBreast cancer patientsSera of patientsMarkers of angiogenesisSandwich enzyme-linked immunoassayEnzyme-linked immunoassayCollagen IV concentrationVascular basement membraneClinical stageHER2 statusHealthy controlsSignificant further increaseHealthy volunteersPatientsChemotherapyStage IIUse of genomic grade index (GGI) to predict pathologic response to preoperative chemotherapy in breast cancer
Symmans W, Hatzis C, Liedtke C, Desmedt C, Valero V, Kuerer H, Hortobagyi G, Piccart- Gebhart M, Pusztai L, Sotiriou C. Use of genomic grade index (GGI) to predict pathologic response to preoperative chemotherapy in breast cancer. Journal Of Clinical Oncology 2008, 26: 541-541. DOI: 10.1200/jco.2008.26.15_suppl.541.Peer-Reviewed Original ResearchGenomic predictors of pathologic response to preoperative chemotherapy for triple-negative and ER-positive/HER2-negative breast cancers
Hatzis C, Symmans W, Lin F, Zheng B, Yan K, Booser D, Gong Y, Valero V, Hortobagyi G, Pusztai L. Genomic predictors of pathologic response to preoperative chemotherapy for triple-negative and ER-positive/HER2-negative breast cancers. Journal Of Clinical Oncology 2008, 26: 571-571. DOI: 10.1200/jco.2008.26.15_suppl.571.Peer-Reviewed Original ResearchInter-pathologist agreement of residual cancer burden (rcb) assessment in breast cancer after treatment with preoperative chemotherapy
Peintinger F, Hatzis C, Morkowski J, Hubbard R, Albarracin C, Qureshi G, Pusztai L, Symmans W. Inter-pathologist agreement of residual cancer burden (rcb) assessment in breast cancer after treatment with preoperative chemotherapy. Journal Of Clinical Oncology 2008, 26: 576-576. DOI: 10.1200/jco.2008.26.15_suppl.576.Peer-Reviewed Original ResearchPreoperative chemotherapyBreast cancerBurden assessmentInter-pathologist agreementChemotherapyCancer
2007
CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer
Esteva FJ, Wang J, Lin F, Mejia JA, Yan K, Altundag K, Valero V, Buzdar AU, Hortobagyi GN, Symmans WF, Pusztai L. CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer. Breast Cancer Research 2007, 9: r87. PMID: 18086299, PMCID: PMC2246190, DOI: 10.1186/bcr1836.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBiopsy, Fine-NeedleBreast NeoplasmsCD40 AntigensCyclophosphamideEpirubicinFemaleFluorouracilGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMastectomyMastectomy, Modified RadicalMastectomy, SegmentalMiddle AgedNeoadjuvant TherapyNeoplasm StagingNeoplasm, ResidualPaclitaxelPredictive Value of TestsReceptor, ErbB-2RNA, MessengerSignal TransductionTranscription, GeneticTrastuzumabTreatment OutcomeUp-RegulationConceptsPathologic complete responseBreast cancerIIIA breast cancerFine-needle aspirationConcomitant paclitaxelConcomitant trastuzumabFEC therapyPreoperative trastuzumabPreoperative chemotherapyPrimary endpointComplete responseNodal statusResidual cancerTumor sizeTumor responseNuclear gradeReceptor mRNAMolecular predictorsTrastuzumabStage IIGreater riskLow expressionCancerCyclophosphamidePatientsThirty-Gene Pharmacogenomic Test Correlates with Residual Cancer Burden after Preoperative Chemotherapy for Breast Cancer
Peintinger F, Anderson K, Mazouni C, Kuerer HM, Hatzis C, Lin F, Hortobagyi GN, Symmans WF, Pusztai L. Thirty-Gene Pharmacogenomic Test Correlates with Residual Cancer Burden after Preoperative Chemotherapy for Breast Cancer. Clinical Cancer Research 2007, 13: 4078-4082. PMID: 17634532, DOI: 10.1158/1078-0432.ccr-06-2600.Peer-Reviewed Original ResearchConceptsResidual cancer burdenRCB 0RCB scoreRCB-IIICancer burdenPharmacogenomic testsRCB-IIPreoperative chemotherapyRCB classBreast cancerChemotherapy-resistant diseaseLymph node featuresPathologic reviewPathologic responseResidual tumorStage IPatientsIII groupChemotherapyI groupGene expression profilingCategorical variablesMean scoreScoresCancerHER2 expression and efficacy of preoperative paclitaxel and 5-fluorouracil, cyclophosphamide, doxorubicin chemotherapy in breast cancer
Pusztai L, Andre F, Mazouni C, Liedtke C, Kau S, Frye D, Green M, Gonzalez-Angulo A, Symmans W, Hortobagyi G. HER2 expression and efficacy of preoperative paclitaxel and 5-fluorouracil, cyclophosphamide, doxorubicin chemotherapy in breast cancer. Journal Of Clinical Oncology 2007, 25: 548-548. DOI: 10.1200/jco.2007.25.18_suppl.548.Peer-Reviewed Original ResearchPathologic complete responseHER2 overexpressionPCR rateBreast cancerER- cancersHER2 expressionHER2- diseaseRelapse-free survival rateER-negative statusWeekly paclitaxel regimenMicrotubule associated protein tauHigh nuclear gradePaclitaxel regimenPreoperative paclitaxelFAC chemotherapyPreoperative chemotherapyComplete responseHER2 tumorsHER2 statusDoxorubicin chemotherapyNuclear gradeRetrospective analysisPatientsTaxane sensitivitySurvival rateEffect on patient outcome of residual DCIS in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy
Mazouni C, Peintinger F, Wan-Kau S, Andre F, Gonzalez-Angulo A, Symmans F, Meric-Bernstam F, Valero V, Hortobagyi G, Pusztai L. Effect on patient outcome of residual DCIS in patients with complete eradication of invasive breast cancer after neoadjuvant chemotherapy. Journal Of Clinical Oncology 2007, 25: 530-530. DOI: 10.1200/jco.2007.25.18_suppl.530.Peer-Reviewed Original ResearchResidual invasive cancerInvasive cancerResidual DCISSurvival rateNeoadjuvant chemotherapyComplete eradicationDisease-free survival ratesLocal recurrence-free survivalRecurrence-free survival ratesUT MD Anderson Cancer CenterMD Anderson Cancer CenterResidual ductal carcinomaOutcomes of patientsPathologic complete responseRate of patientsInvasive breast cancerLocal recurrence rateOverall survival rateRecurrence-free survivalBreast cancer patientsAnderson Cancer CenterInclusion of casesPatients 78Residual invasivePreoperative chemotherapyHER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer
Andre F, Mazouni C, Liedtke C, Kau SW, Frye D, Green M, Gonzalez-Angulo AM, Symmans WF, Hortobagyi GN, Pusztai L. HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer. Breast Cancer Research And Treatment 2007, 108: 183-190. PMID: 17468948, DOI: 10.1007/s10549-007-9594-8.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCyclophosphamideDisease-Free SurvivalDNA Topoisomerases, Type IIDNA-Binding ProteinsDoxorubicinDrug Administration ScheduleFemaleFluorouracilGene AmplificationGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedNeoadjuvant TherapyNeoplasm StagingOligonucleotide Array Sequence AnalysisPaclitaxelPatient SelectionPoly-ADP-Ribose Binding ProteinsReceptor, ErbB-2Receptors, EstrogenRetrospective StudiesRNA, MessengerTau ProteinsTime FactorsTreatment OutcomeConceptsPathologic complete responseHER2 overexpressionBreast cancerFAC chemotherapyPCR rateER statusHER2 expressionRelapse-free survival rateHER2-overexpressing breast cancerMicrotubule associated protein tauER-positive cancersEstrogen receptor statusPreoperative chemotherapyComplete responseHER2 tumorsMethodsRetrospective analysisReceptor statusPatientsSurvival rateMultivariate analysisWeekly scheduleMAP-tauProtein tauCancerChemotherapyInclusion of taxanes, particularly weekly paclitaxel, in preoperative chemotherapy improves pathologic complete response rate in estrogen receptor-positive breast cancers
Mazouni C, Kau S, Frye D, Andre F, Kuerer H, Buchholz T, Symmans W, Anderson K, Hess K, Gonzalez-Angulo A, Hortobagyi G, Buzdar A, Pusztai L. Inclusion of taxanes, particularly weekly paclitaxel, in preoperative chemotherapy improves pathologic complete response rate in estrogen receptor-positive breast cancers. Annals Of Oncology 2007, 18: 874-880. PMID: 17293601, DOI: 10.1093/annonc/mdm008.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsBridged-Ring CompoundsChemotherapy, AdjuvantCyclophosphamideDoxorubicinDrug Administration ScheduleFemaleFluorouracilHumansMiddle AgedNeoplasms, Hormone-DependentPaclitaxelPrognosisReceptors, EstrogenSurvival AnalysisTaxoidsTumor BurdenConceptsPathologic complete response rateComplete response rateER-negative tumorsPreoperative chemotherapyPCR rateER statusBreast cancerResponse rateEstrogen receptor-positive breast cancerReceptor-positive breast cancerMD Anderson Cancer CenterBreast cancer benefitER-negative statusInclusion of taxanesER-negative patientsER-positive patientsER-positive tumorsNeo-adjuvant therapyType of regimenClinical tumor sizeSubset of patientsCox regression analysisER-negative cancersPositive breast cancerAnderson Cancer Center