2024
Pathologic complete response (pCR) rates for patients with HR+/HER2- high-risk, early-stage breast cancer (EBC) by clinical and molecular features in the phase II I-SPY2 clinical trial
Huppert L, Wolf D, Yau C, Brown-Swigart L, Hirst G, Isaacs C, Pusztai L, Pohlmann P, DeMichele A, Shatsky R, Yee D, Thomas A, Nanda R, Perlmutter J, Heditsian D, Hylton N, Symmans F, Veer L, Esserman L, Rugo H. Pathologic complete response (pCR) rates for patients with HR+/HER2- high-risk, early-stage breast cancer (EBC) by clinical and molecular features in the phase II I-SPY2 clinical trial. Annals Of Oncology 2024 PMID: 39477071, DOI: 10.1016/j.annonc.2024.10.018.Peer-Reviewed Original ResearchDistant recurrence-free survivalEarly-stage breast cancerPathological complete responsePathologic complete response rateClinical/molecular featuresComplete responseER-positiveBreast cancerRate of pathological complete responseResponse to neoadjuvant chemotherapyRecurrence-free survivalI-SPY2 trialOptimal treatment selectionNeoadjuvant armER/PR statusLobular histologyNeoadjuvant chemotherapyIII diseaseImmune signaturesNegative diseaseOptimal therapyI-SPY2Excellent outcomesTreatment armsFollow-upRecurrence score gene axes scores and outcomes by race and ethnicity in the RxPONDER trial.
Abdou Y, Hoag J, Barlow W, Gralow J, Meric-Bernstam F, Albain K, Hayes D, Lin N, Perez E, Goldstein L, Chia S, Dhesy-Thind S, Rastogi P, Schott A, Racz J, Tripathy D, Hortobagyi G, Pusztai L, Sharma P, Kalinsky K. Recurrence score gene axes scores and outcomes by race and ethnicity in the RxPONDER trial. Journal Of Clinical Oncology 2024, 42: 515-515. DOI: 10.1200/jco.2024.42.16_suppl.515.Peer-Reviewed Original ResearchInvasive disease-free survivalNon-Hispanic whitesRecurrence scoreRacial/ethnic groupsTumor biologyRxPONDER trialNon-Hispanic Black (NHBBreast cancer outcomesDisease-free survivalMedian follow-upCox regression modelsAssociated with outcomeCancer-related genesSignificant healthcare concernCancer outcomesMenopausal statusPrognostic valueInferior outcomesHER2 signalingUnadjusted analysisTreatment armsFollow-upImpact of raceNHBHER2
2023
Correlation of HER2 low status in I-SPY2 with molecular subtype, response, and survival.
Rugo H, Wolf D, Yau C, Petricoin E, Pohlmann P, Pusztai L, Symmans W, Borowsky A, Finestone S, Yee D, Hylton N, van 't Veer L, Esserman L, DeMichele A. Correlation of HER2 low status in I-SPY2 with molecular subtype, response, and survival. Journal Of Clinical Oncology 2023, 41: 514-514. DOI: 10.1200/jco.2023.41.16_suppl.514.Peer-Reviewed Original ResearchDistant recurrence-free survivalPathologic complete responseBreast cancerFisher's exact testExact testMolecular subtypesHER2-negative breast cancerHigh-risk breast cancerRisk breast cancerMetastatic breast cancerRecurrence-free survivalTN breast cancerRecurrence-free survival dataCox proportional hazardsHER2 gene amplificationI-SPY2TN diseaseFree survivalOverall survivalComplete responseHazard ratioTrastuzumab deruxtecanEndocrine sensitivityT-DXdTreatment armsEvaluation 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
2022
Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial.
Huppert L, Rugo H, Pusztai L, Mukhtar R, Chien A, Yau C, Wolf D, Berry D, van 't Veer L, Yee D, DeMichele A, Esserman L, Consortium I. Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial. Journal Of Clinical Oncology 2022, 40: 504-504. DOI: 10.1200/jco.2022.40.16_suppl.504.Peer-Reviewed Original ResearchI-SPY2 trialInvestigational agentsMolecular subtypesNodal statusPathologic complete response rateMultiple investigational agentsComplete response ratePhase 3 trialHER2- breast cancerLuminal statusNeoadjuvant therapyPrimary endpointImmune signaturesPCR rateTreatment armsHeterogenous diseaseBC therapySubtype 5Breast cancerImmune biologyResponse ratePembrolizumabHormone receptorsDiseaseTrials
2021
Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
Yee D, Isaacs C, Wolf DM, Yau C, Haluska P, Giridhar KV, Forero-Torres A, Jo Chien A, Wallace AM, Pusztai L, Albain KS, Ellis ED, Beckwith H, Haley BB, Elias AD, Boughey JC, Kemmer K, Yung RL, Pohlmann PR, Tripathy D, Clark AS, Han HS, Nanda R, Khan QJ, Edmiston KK, Petricoin EF, Stringer-Reasor E, Falkson CI, Majure M, Mukhtar RA, Helsten TL, Moulder SL, Robinson PA, Wulfkuhle JD, Brown-Swigart L, Buxton M, Clennell JL, Paoloni M, Sanil A, Berry S, Asare SM, Wilson A, Hirst GL, Singhrao R, Asare AL, Matthews JB, Hylton NM, DeMichele A, Melisko M, Perlmutter J, Rugo HS, Fraser Symmans W, van‘t Veer L, Berry DA, Esserman LJ. Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer. Npj Breast Cancer 2021, 7: 131. PMID: 34611148, PMCID: PMC8492731, DOI: 10.1038/s41523-021-00337-2.Peer-Reviewed Original ResearchBreast cancerPredictive biomarkersPathologic complete response rateStage 2/3 breast cancerHER2-negative breast cancerPhase 2 clinical trialType I insulin-like growth factor receptorDrug-induced hyperglycemiaStandard neoadjuvant therapyComplete response rateUse of metforminI insulin-like growth factor receptorInsulin-like growth factor receptorPutative predictive biomarkersGrowth factor receptorI-SPY2Neoadjuvant therapyNeoadjuvant treatmentTreatment armsClinical trialsElevated hemoglobinNovel agentsGanitumabResponse rateCare paclitaxel
2017
Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06)
Ponde N, Bradbury I, Lambertini M, Ewer M, Campbell C, Ameels H, Zardavas D, Di Cosimo S, Baselga J, Huober J, Izquierdo M, Fumagalli D, Bozovic-Spasojevic I, Maetens M, Harbeck N, Pusztai L, Berghorn M, Im YH, Borrego MR, Chen DR, Rodeheffer R, Piccart M, Suter T, de Azambuja E. Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06). Breast Cancer Research And Treatment 2017, 168: 631-638. PMID: 29280043, PMCID: PMC5843537, DOI: 10.1007/s10549-017-4628-3.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyNT-proBNPBiomarker elevationCardiac toxicityEarly predictorHER2-positive early-stage breast cancerEarly-stage breast cancerAnthracycline-naïve patientsEarly cardiac toxicityLevels of TnTNT-proBNP elevationBrain natriuretic peptideBreast cancer patientsNeoALTTO trialWeekly paclitaxelCardiac dysfunctionTreatment armsCardiac damageNatriuretic peptideCancer patientsCardiac biomarkersBreast cancerPatientsTroponin TAmino-terminal fragmentRNA 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
2016
Relationship between Complete Pathologic Response to Neoadjuvant Chemotherapy and Survival in Triple-Negative Breast Cancer
Hatzis C, Symmans WF, Zhang Y, Gould RE, Moulder SL, Hunt KK, Abu-Khalaf M, Hofstatter EW, Lannin D, Chagpar AB, Pusztai L. Relationship between Complete Pathologic Response to Neoadjuvant Chemotherapy and Survival in Triple-Negative Breast Cancer. Clinical Cancer Research 2016, 22: 26-33. PMID: 26286912, DOI: 10.1158/1078-0432.ccr-14-3304.Peer-Reviewed Original ResearchConceptsPathologic complete responseRecurrence-free survivalTriple-negative breast cancerSurvival benefitNeoadjuvant trialsNeoadjuvant chemotherapyTrial populationBaseline prognosisBreast cancerOverall survival benefitComplete pathologic responseSignificant survival benefitPostneoadjuvant therapyPCR rateComplete responseImproved survivalPathologic responseSurvival improvementTreatment armsPatient survivalResidual diseaseControl armPrognostic variablesPatientsTrials
2013
Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early Stage Breast Cancer and Evaluation of βIII‐Tubulin Expression as a Predictive Marker
Saura C, Tseng L, Chan S, Chacko RT, Campone M, Manikhas A, Nag SM, Leichman CG, Dasappa L, Fasching PA, de Mendoza F, Symmans WF, Liu D, Mukhopadhyay P, Horak C, Xing G, Pusztai L. Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early Stage Breast Cancer and Evaluation of βIII‐Tubulin Expression as a Predictive Marker. The Oncologist 2013, 18: 787-794. PMID: 23853246, PMCID: PMC3720631, DOI: 10.1634/theoncologist.2013-0075.Peer-Reviewed Original ResearchConceptsEarly-stage breast cancerStage breast cancerPathologic complete responseΒIII-tubulin expressionBreast cancerTreatment armsWeekly paclitaxelPositive patientsPredictive markerNeoadjuvant doxorubicin/cyclophosphamideRandomized phase II trialΒIII-tubulinCommon nonhematologic toxicitiesDoxorubicin/cyclophosphamideInvasive breast adenocarcinomaPhase II trialCore needle biopsyCycles of ACHigh response rateSignificant differencesNeoadjuvant cyclophosphamideNonhematologic toxicityNeoadjuvant treatmentII trialNegative patientsBiomarker Analysis of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early-Stage Breast Cancer
Horak CE, Pusztai L, Xing G, Trifan OC, Saura C, Tseng LM, Chan S, Welcher R, Liu D. Biomarker Analysis of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early-Stage Breast Cancer. Clinical Cancer Research 2013, 19: 1587-1595. PMID: 23340299, DOI: 10.1158/1078-0432.ccr-12-1359.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Biomarkers, TumorBreast NeoplasmsCyclophosphamideDoxorubicinEpothilonesFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMicrofilament ProteinsMicrotubule-Associated ProteinsNeoadjuvant TherapyNeoplasm ProteinsNuclear ProteinsPaclitaxelPrognosisTubulinConceptsMDR1 protein expressionNeoadjuvant doxorubicin/cyclophosphamideEarly-stage breast cancerDoxorubicin/cyclophosphamidePositive patientsProtein expressionTreatment armsBreast cancerPathologic complete response rateEfficacy of ixabepiloneInvasive breast adenocarcinomaComplete response ratePhase II trialCore needle biopsyRates of pCRΒIII-tubulin proteinNeoadjuvant settingII trialNegative patientsGene expressionPrimary cancerPredictive biomarkersPredictive markerRisk ratioNeedle biopsy
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 status
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