2010
Evaluation 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 subsets
2009
Evaluation of the Predictive Performance and Regimen Specificity of a 30-Gene Predictor of Pathologic Complete Response in a Prospective Randomized Neoadjuvant Clinical Trial for Stage I-III Breast Cancer.
Tabchy A, Symmans W, Valero V, Vidaurre T, Lluch A, Qi Y, Souchon E, Barajas-Figueroa L, Gomez H, Martin M, Coutant C, Hess K, Hortobagyi G, Pusztai L. Evaluation of the Predictive Performance and Regimen Specificity of a 30-Gene Predictor of Pathologic Complete Response in a Prospective Randomized Neoadjuvant Clinical Trial for Stage I-III Breast Cancer. Cancer Research 2009, 69: 101-101. DOI: 10.1158/0008-5472.sabcs-09-101.Peer-Reviewed Original ResearchPathologic complete responsePositive predictive valueCourses of FACFAC armWeekly paclitaxelFAC chemotherapyPCR rateComplete responseMultigene predictorsTreatment armsBreast cancerStage IPathologic complete response rateGenomic predictorsComplete response rateNeoadjuvant clinical trialsEstrogen receptor statusNegative predictive value 88Treatment response predictionFAC regimenNPV 92Neoadjuvant chemotherapyOnly chemotherapyCyclophosphamide chemotherapyNodal statusGenomic Grade Index Is Associated With Response to Chemotherapy in Patients With Breast Cancer
Liedtke C, Hatzis C, Symmans WF, Desmedt C, Haibe-Kains B, Valero V, Kuerer H, Hortobagyi GN, Piccart-Gebhart M, Sotiriou C, Pusztai L. Genomic Grade Index Is Associated With Response to Chemotherapy in Patients With Breast Cancer. Journal Of Clinical Oncology 2009, 27: 3185-3191. PMID: 19364972, PMCID: PMC2716940, DOI: 10.1200/jco.2008.18.5934.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveBreast NeoplasmsCyclophosphamideDoxorubicinDrug Resistance, NeoplasmFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyOligonucleotide Array Sequence AnalysisPaclitaxelReceptors, EstrogenROC CurveTreatment OutcomeConceptsGenomic grade indexER-positive patientsRelapse-free survivalPathologic responseNeoadjuvant paclitaxelCyclophosphamide chemotherapyBreast cancerWorse distant relapse-free survivalDistant relapse-free survivalSystemic adjuvant therapyPathologic complete responseFine-needle aspiration biopsyGrade 3 tumorsER-negative cancersER-positive cancersGrade 1 tumorsGrade 2 tumorsMinimal residual diseaseHistological tumor gradeAdjuvant therapyNeoadjuvant chemotherapyComplete responseWorse survivalClinical parametersResidual disease
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
2007
Neoadjuvant Therapy with Paclitaxel followed by 5-Fluorouracil, Epirubicin, and Cyclophosphamide Chemotherapy and Concurrent Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer: An Update of the Initial Randomized Study Population and Data of Additional Patients Treated with the Same Regimen
Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant Therapy with Paclitaxel followed by 5-Fluorouracil, Epirubicin, and Cyclophosphamide Chemotherapy and Concurrent Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer: An Update of the Initial Randomized Study Population and Data of Additional Patients Treated with the Same Regimen. Clinical Cancer Research 2007, 13: 228-233. PMID: 17200359, DOI: 10.1158/1078-0432.ccr-06-1345.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptorPathologic CR rateEpidermal growth factor receptorConcurrent trastuzumabGrowth factor receptorCR rateEfficacy dataBreast cancerStudy populationHigher pathologic complete remission rateSecond cohortPathologic complete remission rateCardiac safety dataCycles of FECCycles of paclitaxelOperable breast cancerComplete remission rateDisease-free survivalFactor receptorBreast cancer patientsNew safety concernsSame chemotherapyWeekly trastuzumabCyclophosphamide chemotherapyNeoadjuvant therapy
2006
Pharmacogenomic analysis of needle biopsies obtained before preoperative docetaxel/capecitabine/FEC (TX/FEC) chemotherapy for breast cancer
Holmes F, O’Shaughnessy J, Hellerstedt B, Pippen J, Vukelja S, Kocs D, Asmar L, Fenske E, Lin F, Symmans W, Pusztai L. Pharmacogenomic analysis of needle biopsies obtained before preoperative docetaxel/capecitabine/FEC (TX/FEC) chemotherapy for breast cancer. Journal Of Clinical Oncology 2006, 24: 10595-10595. DOI: 10.1200/jco.2006.24.18_suppl.10595.Peer-Reviewed Original ResearchPharmacogenomic analysis of HER2 amplified breast cancer treated with preoperative trastuzumab and paclitaxel, 5-fluorouracil, epirubicin, cyclophosphamide (T/FEC) chemotherapy
Esteva F, Anderson K, Lin F, Nahta R, Mejia J, Altundag K, Buzdar A, Hortobagyi G, Symmans W, Pusztai L. Pharmacogenomic analysis of HER2 amplified breast cancer treated with preoperative trastuzumab and paclitaxel, 5-fluorouracil, epirubicin, cyclophosphamide (T/FEC) chemotherapy. Journal Of Clinical Oncology 2006, 24: 545-545. DOI: 10.1200/jco.2006.24.18_suppl.545.Peer-Reviewed Original ResearchBreast cancerOverall pathologic complete response ratePathologic complete response rateTrastuzumab-resistant cell linesAbsence of trastuzumabOnly preoperative chemotherapyComplete response rateReceptor mRNA expressionFine-needle aspirationConcomitant trastuzumabFEC chemotherapyPreoperative trastuzumabQuantitative estrogenCyclophosphamide chemotherapyPreoperative chemotherapyNodal statusResidual diseaseTumor sizeClinical variablesNuclear gradeNeedle aspirationPharmacogenomic predictorsMolecular predictorsResponse rateTrastuzumab
2005
Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy
Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, Hess KR, Stec J, Ayers M, Wagner P, Morandi P, Fan C, Rabiul I, Ross JS, Hortobagyi GN, Pusztai L. Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy. Clinical Cancer Research 2005, 11: 5678-5685. PMID: 16115903, DOI: 10.1158/1078-0432.ccr-04-2421.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiopsy, NeedleBreastBreast NeoplasmsCluster AnalysisDoxorubicinFemaleFluorouracilGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedMultivariate AnalysisOligonucleotide Array Sequence AnalysisPaclitaxelPredictive Value of TestsPreoperative CareReceptor, ErbB-2ConceptsPathologic complete responseComplete responsePreoperative chemotherapyBreast cancerEstrogen receptor-negative subtypesPathologic CR rateEstrogen receptor statusBasal-like groupDifferent molecular subtypesFine-needle aspirationAffymetrix U133A microarraysPreoperative paclitaxelCyclophosphamide chemotherapyReceptor statusCR rateLuminal tumorsDifferent prognosisNuclear gradeMolecular subtypesNeedle aspirationChemotherapy sensitivityChemotherapyCancerMolecular classificationHuman tumorsEpidermal growth factor receptor expression correlates with poor survival in patients who have breast carcinoma treated with doxorubicin‐based neoadjuvant chemotherapy
Buchholz TA, Tu X, Ang KK, Esteva FJ, Kuerer HM, Pusztai L, Cristofanilli M, Singletary SE, Hortobagyi GN, Sahin AA. Epidermal growth factor receptor expression correlates with poor survival in patients who have breast carcinoma treated with doxorubicin‐based neoadjuvant chemotherapy. Cancer 2005, 104: 676-681. PMID: 15981280, DOI: 10.1002/cncr.21217.Peer-Reviewed Original ResearchMeSH KeywordsAntibiotics, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicCyclophosphamideDisease-Free SurvivalDoxorubicinErbB ReceptorsFemaleFluorouracilHumansImmunohistochemistryNeoadjuvant TherapyPrognosisRandomized Controlled Trials as TopicSurvival AnalysisConceptsEpidermal growth factor receptorBreast carcinomaEGFR expressionAnthracycline chemotherapyLymph nodesEpidermal growth factor receptor expression correlatesSurvival ratePathologic complete response ratePretreatment tumor tissue samplesDisease-free survival ratesCox regression analysis modelComplete response rateEGFR-negative tumorsEGFR-positive diseasePositive lymph nodesAdvanced breast carcinomaMore lymph nodesOutcomes of patientsOverall survival rateProgesterone receptor statusEGFR-positive tumorsTumor tissue samplesKnowledge of outcomesGrowth factor receptorCyclophosphamide chemotherapy
2004
Gene Expression Profiles Predict Complete Pathologic Response to Neoadjuvant Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide Chemotherapy in Breast Cancer
Ayers M, Symmans W, Stec J, Damokosh A, Clark E, Hess K, Lecocke M, Metivier J, Booser D, Ibrahim N, Valero V, Royce M, Arun B, Whitman G, Ross J, Sneige N, Hortobagyi G, Pusztai L. Gene Expression Profiles Predict Complete Pathologic Response to Neoadjuvant Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide Chemotherapy in Breast Cancer. Journal Of Clinical Oncology 2004, 22: 2284-2293. PMID: 15136595, DOI: 10.1200/jco.2004.05.166.Peer-Reviewed Original ResearchConceptsPathologic complete responseBreast cancerNeoadjuvant therapyClinical resultsPredictive valueCompletion of chemotherapySequential weekly paclitaxelComplete pathologic responseNeoadjuvant chemotherapy regimenPercent of patientsPatients' clinical resultsExpected response rateFine-needle aspirationNegative predictive valuePositive predictive valueNeoadjuvant paclitaxelChemotherapy regimenWeekly paclitaxelCyclophosphamide chemotherapyUnselected patientsComplete responsePathologic responseInvasive cancerResponse ratePatientsPharmacoproteomic analysis of prechemotherapy and postchemotherapy plasma samples from patients receiving neoadjuvant or adjuvant chemotherapy for breast carcinoma
Pusztai L, Gregory BW, Baggerly KA, Peng B, Koomen J, Kuerer HM, Esteva FJ, Symmans WF, Wagner P, Hortobagyi GN, Laronga C, Semmes OJ, Wright GL, Drake RR, Vlahou A. Pharmacoproteomic analysis of prechemotherapy and postchemotherapy plasma samples from patients receiving neoadjuvant or adjuvant chemotherapy for breast carcinoma. Cancer 2004, 100: 1814-1822. PMID: 15112261, DOI: 10.1002/cncr.20203.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBiopsy, NeedleBreast NeoplasmsCase-Control StudiesChemotherapy, AdjuvantCyclophosphamideDoxorubicinDrug Administration ScheduleFemaleFluorouracilHumansMastectomyMiddle AgedNeoadjuvant TherapyNeoplasm StagingPaclitaxelPostoperative CarePreoperative CareProteomicsRisk AssessmentSensitivity and SpecificitySurvival AnalysisTreatment OutcomeConceptsBreast carcinomaHealthy womenPreoperative chemotherapyFinal tumor responseSubset of patientsDay 3 posttreatmentAdjuvant chemotherapyPostoperative chemotherapyCyclophosphamide chemotherapyFAC chemotherapyMicrometastatic diseasePaclitaxel chemotherapyNormal womenTumor responsePlasma profilesHealthy volunteersChemotherapyPatientsStage ICarcinomaDay 0Single courseWomenPlasma samplesCandidate markersChange in tumor cellularity of breast carcinoma after neoadjuvant chemotherapy as a variable in the pathologic assessment of response
Rajan R, Poniecka A, Smith TL, Yang Y, Frye D, Pusztai L, Fiterman DJ, Gal‐Gombos E, Whitman G, Rouzier R, Green M, Kuerer H, Buzdar AU, Hortobagyi GN, Symmans WF. Change in tumor cellularity of breast carcinoma after neoadjuvant chemotherapy as a variable in the pathologic assessment of response. Cancer 2004, 100: 1365-1373. PMID: 15042669, DOI: 10.1002/cncr.20134.Peer-Reviewed Original ResearchConceptsResidual tumor sizeCore needle biopsyNeoadjuvant chemotherapyTumor sizeResection specimensNeedle biopsyBreast carcinomaTumor cellularityClinical responsePathologic responseControl groupDiagnostic core needle biopsyGreatest dimensionPrimary surgical managementResidual primary tumorResidual tumor categoriesComplete pathologic responseWeeks of diagnosisResidual tumor groupEosin-stained tissue sectionsCyclophosphamide chemotherapyPartial responsePathologic assessmentPathologic evaluationPathologic sizePrognostic significance of phosphorylated P38 mitogen‐activated protein kinase and HER‐2 expression in lymph node‐positive breast carcinoma
Esteva FJ, Sahin AA, Smith TL, Yang Y, Pusztai L, Nahta R, Buchholz TA, Buzdar AU, Hortobagyi GN, Bacus SS. Prognostic significance of phosphorylated P38 mitogen‐activated protein kinase and HER‐2 expression in lymph node‐positive breast carcinoma. Cancer 2004, 100: 499-506. PMID: 14745865, DOI: 10.1002/cncr.11940.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBiopsy, NeedleBreast NeoplasmsCombined Modality TherapyFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryLymph NodesMastectomyMiddle AgedMitogen-Activated Protein KinasesNeoplasm StagingP38 Mitogen-Activated Protein KinasesProbabilityPrognosisProportional Hazards ModelsReceptor, ErbB-2Risk AssessmentSensitivity and SpecificitySurvival AnalysisTreatment OutcomeConceptsLymph node positive breast carcinomaNode-positive breast carcinomaProgression-free survivalP-p38 MAPKShorter progression-free survivalHER-2 expressionP-p38 MAPK expressionBreast carcinomaAdjuvant chemotherapyMAPK expressionKi-67Phosphorylated p38 MAPK expressionInitial cancer surgeryPrimary breast carcinomaInvasive breast carcinomaP38 MAPK expressionP38 mitogen-activated protein kinase phosphorylationPhosphorylated p38 mitogen-activated protein kinaseMitogen-activated protein kinase phosphorylationBreast carcinoma cellsAdjuvant fluorouracilMedian followCyclophosphamide chemotherapyCancer surgeryPoor outcome