2024
Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522☆
Pusztai L, Denkert C, O’Shaughnessy J, Cortes J, Dent R, McArthur H, Kümmel S, Bergh J, Park Y, Hui R, Harbeck N, Takahashi M, Untch M, Fasching P, Cardoso F, Zhu Y, Pan W, Tryfonidis K, Schmid P. Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522☆. Annals Of Oncology 2024, 35: 429-436. PMID: 38369015, DOI: 10.1016/j.annonc.2024.02.002.Peer-Reviewed Original ResearchTriple-negative breast cancerEvent-free survivalPathological complete responseResidual cancer burdenEarly-stage triple-negative breast cancerEvent-free survival eventsPembrolizumab groupRCB-2KEYNOTE-522Neoadjuvant pembrolizumabRCB-0Central nervous system recurrenceCancer burdenCycles of paclitaxelIncreased pCR ratePembrolizumab to chemotherapyCycles of doxorubicinCox regression modelsRCB-1Adjuvant pembrolizumabDistant recurrencePCR rateResidual diseaseSystemic recurrenceComplete response
2023
Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials
Rediti M, Fernandez-Martinez A, Venet D, Rothé F, Hoadley K, Parker J, Singh B, Campbell J, Ballman K, Hillman D, Winer E, El-Abed S, Piccart M, Di Cosimo S, Symmans W, Krop I, Salgado R, Loi S, Pusztai L, Perou C, Carey L, Sotiriou C. Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials. Nature Communications 2023, 14: 7053. PMID: 37923752, PMCID: PMC10624889, DOI: 10.1038/s41467-023-42635-2.Peer-Reviewed Original ResearchConceptsEvent-free survivalHER2-positive breast cancerPathological complete responseCALGB 40601Breast cancerBreast pathological complete responseStromal tumor-infiltrating lymphocytesHormone receptor statusPhase III trialsClinical nodal statusIndependent prognostic factorTumor-infiltrating lymphocytesIdentification of patientsBreast cancer prognosisT cell receptorNeoadjuvant paclitaxelNeoadjuvant therapyIII trialsNodal statusComplete responsePrognostic factorsPrognostic scoreReceptor statusClinicopathological featuresResidual diseaseTreatment efficacy score: a better surrogate for arm-level survival differences in neoadjuvant breast cancer trials?
Chehayeb R, Kahn A, Pusztai L. Treatment efficacy score: a better surrogate for arm-level survival differences in neoadjuvant breast cancer trials? Future Oncology 2023, 19: 1945-1951. PMID: 37767612, DOI: 10.2217/fon-2022-1203.Peer-Reviewed Original ResearchExcellent long-term survivalNeoadjuvant breast cancer trialsResidual cancer burden scorePathologic complete responseBreast cancer trialsLong-term survivalNeoadjuvant chemotherapyPathologic responseComplete responseSurvival improvementBurden scoreResidual diseaseTrial armsSurvival differencesCancer trialsBreast cancerTreatment efficacyStage IIGood surrogateEfficacy scoresTrialsSurvivalScoresRate differencesChemotherapyImage analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial
Fanucci K, Bai Y, Pelekanou V, Nahleh Z, Shafi S, Burela S, Barlow W, Sharma P, Thompson A, Godwin A, Rimm D, Hortobagyi G, Liu Y, Wang L, Wei W, Pusztai L, Blenman K. Image analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial. Npj Breast Cancer 2023, 9: 38. PMID: 37179362, PMCID: PMC10182981, DOI: 10.1038/s41523-023-00535-0.Peer-Reviewed Original ResearchPathologic complete responseBreast cancerComplete responseTIL scoreBreast Cancer Pathologic Complete ResponseTumor-infiltrating lymphocyte scoresEvent-free survivalNeoadjuvant chemotherapy trialsLymphocyte measurementsLymphocyte scoreNeoadjuvant chemotherapyChemotherapy trialsMean pretreatmentResidual diseaseTIL quantificationPredictive valuePretreatment samplesResponse discriminationScoresStrong positive correlationPositive correlationP018 TROPION-Breast03: Datopotamab deruxtecan (Dato-DXd) ± durvalumab vs investigator’s choice of therapy (ICT) for triple-negative breast cancer (TNBC) with residual disease following neoadjuvant therapy
Bardia A, Pusztai L, Albain K, Kalinsky K, Hershman D, Barlow W, Tokunaga E, Ciruelos E, Loirat D, Isaacs C, Testa L, Dry H, Kozarski R, Maxwell M, Harbeck N, Sharma P. P018 TROPION-Breast03: Datopotamab deruxtecan (Dato-DXd) ± durvalumab vs investigator’s choice of therapy (ICT) for triple-negative breast cancer (TNBC) with residual disease following neoadjuvant therapy. The Breast 2023, 68: s23. DOI: 10.1016/s0960-9776(23)00137-6.Peer-Reviewed Original ResearchResponse to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer
Liedtke C, Mazouni C, Hess K, André F, Tordai A, Mejia J, Symmans W, Gonzalez-Angulo A, Hennessy B, Green M, Cristofanilli M, Hortobagyi G, Pusztai L. Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2023, 41: 1809-1815. PMID: 36989609, DOI: 10.1200/jco.22.02572.Peer-Reviewed Original ResearchTriple-negative breast cancerPathologic complete response rateNeoadjuvant chemotherapyResidual diseaseBreast cancerProgesterone receptorEstrogen receptorHuman epidermal growth factor receptor 2 (HER2) expressionSurvival rateEpidermal growth factor receptor 2 expressionProgression-free survival ratesM.D. Anderson Cancer CenterComplete response rateOverall survival rateAnderson Cancer CenterReceptor 2 expressionLong-term survivalBone recurrenceNeoadjuvant therapyPostrecurrence survivalVisceral metastasesWorse OSWorse survivalRelapse rateCancer Center
2022
Prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer (SWOG S0800) using image analysis-based tumor infiltrating lymphocyte measurements.
Blenman K, Fanucci K, Bai Y, Pelekanou V, Nahleh Z, Shafi S, Burela S, Barlow W, Sharma P, Thompson A, Godwin A, Rimm D, Hortobagyi G, Pusztai L. Prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer (SWOG S0800) using image analysis-based tumor infiltrating lymphocyte measurements. Journal Of Clinical Oncology 2022, 40: 594-594. DOI: 10.1200/jco.2022.40.16_suppl.594.Peer-Reviewed Original ResearchPathologic complete responseBreast cancerNeoadjuvant chemotherapyComplete responseTIL scoreResidual diseaseResponse predictive markersBetter EFSBevacizumab benefitLymphocyte measurementsTIL assessmentFree survivalPredictive markerTIL quantificationInternational guidelinesPretreatment samplesLogistic regressionCancerOutcome discriminationChemotherapyScoresContinuous scoresTumorsClinical adoptionStrong positive correlationEvent-free survival by residual cancer burden after neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy for early TNBC: Exploratory analysis from KEYNOTE-522.
Pusztai L, Denkert C, O'Shaughnessy J, Cortes J, Dent R, McArthur H, Kuemmel S, Bergh J, Park Y, Hui R, Harbeck N, Takahashi M, Untch M, Fasching P, Cardoso F, Zhu Y, Pan W, Tryfonidis K, Schmid P. Event-free survival by residual cancer burden after neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy for early TNBC: Exploratory analysis from KEYNOTE-522. Journal Of Clinical Oncology 2022, 40: 503-503. DOI: 10.1200/jco.2022.40.16_suppl.503.Peer-Reviewed Original ResearchPredictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer.
Blenman KRM, Marczyk M, Karn T, Qing T, Li X, Gunasekharan V, Yaghoobi V, Bai Y, Ibrahim EY, Park T, Silber A, Wolf DM, Reisenbichler E, Denkert C, Sinn BV, Rozenblit M, Foldi J, Rimm DL, Loibl S, Pusztai L. Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer. Clinical Cancer Research 2022, 28: 2587-2597. PMID: 35377948, PMCID: PMC9464605, DOI: 10.1158/1078-0432.ccr-21-3215.Peer-Reviewed Original ResearchConceptsBasal-like triple-negative breast cancerPathologic complete responseResidual diseaseNeoadjuvant durvalumabDNA damage repairSomatic mutationsBreast cancerWnt/β-cateninHigh expressionTriple-negative breast cancerBasal-Like TripleDoxorubicin/cyclophosphamideDNA repairTumor mutation burdenRNA sequencingEpithelial-mesenchymal transitionFive-gene signatureB-cell markersCancer driversEnrichment analysisNegative breast cancerDamage repairGene expressionJAK-STATCell cycleImpact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors
Kasi PM, Fehringer G, Taniguchi H, Starling N, Nakamura Y, Kotani D, Powles T, Li BT, Pusztai L, Aushev VN, Kalashnikova E, Sharma S, Malhotra M, Demko ZP, Aleshin A, Rodriguez A, Billings PR, Grothey A, Taieb J, Cunningham D, Yoshino T, Kopetz S. Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors. JCO Precision Oncology 2022, 6: e2100181. PMID: 35263168, PMCID: PMC8926064, DOI: 10.1200/po.21.00181.Peer-Reviewed Original ResearchConceptsMolecular residual diseaseSurrogate end pointsCtDNA testingMRD detectionResidual diseaseClinical trialsCancer recurrenceTumor DNAEnd pointMRD-positive patientsUse of ctDNAHigh-risk categoryCtDNA dynamicsTrial enrichmentAccelerated approvalDifferent cancer typesCancer managementClinical utilityHigh riskClinical practiceSmall cohortSolid tumorsRecurrenceTrial durationTreatment assignment
2020
Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer
Kunst N, Wang SY, Hood A, Mougalian SS, DiGiovanna MP, Adelson K, Pusztai L. Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer. JAMA Network Open 2020, 3: e2027074. PMID: 33226431, PMCID: PMC7684449, DOI: 10.1001/jamanetworkopen.2020.27074.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Agents, PhytogenicBreast NeoplasmsCase-Control StudiesCost-Benefit AnalysisCross-Linking ReagentsDrug Therapy, CombinationFemaleHumansImmunosuppressive AgentsMiddle AgedNeoadjuvant TherapyPaclitaxelQuality-Adjusted Life YearsReceptor, ErbB-2TrastuzumabTubulin ModulatorsUnited StatesConceptsErbB2-positive breast cancerAdjuvant treatment strategiesAdjuvant T-DM1Pathologic complete responseT-DM1Treatment strategiesBreast cancerKATHERINE trialResidual diseaseNeoadjuvant regimenHigher health benefitsHealth care payer perspectiveAdjuvant trastuzumab emtansineAnthracycline/cyclophosphamideDifferent adjuvant therapiesFlatiron Health databaseIncremental cost-effectiveness ratioNeoadjuvant treatment optionsHealth benefitsPositive breast cancerCare payer perspectiveCost-effectiveness ratioBase-case analysisDecision analytic modelH. Patients
2019
Changing frameworks in treatment sequencing of triple-negative and HER2-positive, early-stage breast cancers
Pusztai L, Foldi J, Dhawan A, DiGiovanna MP, Mamounas EP. Changing frameworks in treatment sequencing of triple-negative and HER2-positive, early-stage breast cancers. The Lancet Oncology 2019, 20: e390-e396. PMID: 31267973, DOI: 10.1016/s1470-2045(19)30158-5.Commentaries, Editorials and LettersConceptsEarly-stage breast cancerHER2-positive breast cancerBreast cancerClinical trialsNeoadjuvant chemotherapyEstrogen receptor-negative breast cancerImproved disease-free survivalReceptor-negative breast cancerParticular chemotherapy regimenResidual invasive cancerNeoadjuvant systemic therapyDisease-free survivalImportant clinical trialsAdo-trastuzumab emtansineNegative breast cancerAdjuvant settingKATHERINE trialOperable diseasePostoperative capecitabineChemotherapy regimenMetastatic diseaseSystemic therapyResidual diseaseInvasive cancerTreatment sequencingImmune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial
Li X, Warren S, Pelekanou V, Wali V, Cesano A, Liu M, Danaher P, Elliott N, Nahleh ZA, Hayes DF, Hortobagyi GN, Barlow WE, Hatzis C, Pusztai L. Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial. Journal For ImmunoTherapy Of Cancer 2019, 7: 88. PMID: 30967156, PMCID: PMC6457012, DOI: 10.1186/s40425-019-0563-7.Peer-Reviewed Original ResearchConceptsPathologic complete responseResidual diseaseTIL countGene expression levelsHigh expressionCellular stressNeoadjuvant chemotherapyImmune genesImmune-related genesStromal genesImmune functionImmune microenvironment changesMost immune functionsGenesCell typesPD-L1 protein expressionStem cellsHigher TIL countsPD-L1 expressionExpression levelsPrimary breast cancerT-cell markersImmune cell typesProtein expressionStromal function
2017
Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance
Pelekanou V, Carvajal-Hausdorf DE, Altan M, Wasserman B, Carvajal-Hausdorf C, Wimberly H, Brown J, Lannin D, Pusztai L, Rimm DL. Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Research 2017, 19: 91. PMID: 28784153, PMCID: PMC5547502, DOI: 10.1186/s13058-017-0884-8.Peer-Reviewed Original ResearchConceptsStromal tumor-infiltrating lymphocytesPD-L1 expressionTumor-infiltrating lymphocytesRecurrence-free survivalNeoadjuvant chemotherapyResidual cancer tissueTIL countBreast cancerCancer tissuesDeath ligand 1 (PD-L1) protein expressionNode-positive breast cancerImproved recurrence-free survivalPD-L1 protein expressionHigher TIL countsPD-L1 statusProtein expressionBreast cancer patientsBreast cancer tissuesPost-treatment samplesPrechemotherapy samplesTIL infiltrationResidual cancerImmune markersResidual diseasePatient cohortEffects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial.
Pelekanou V, Barlow W, von Wahlde M, Wasserman B, Lo Y, Hayes D, Hortobagyi G, Gralow J, Tripathy D, Livingston R, Porter P, Nahleh Z, Rimm D, Pusztai L. Effects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial. Journal Of Clinical Oncology 2017, 35: 519-519. DOI: 10.1200/jco.2017.35.15_suppl.519.Peer-Reviewed Original ResearchPD-L1 expressionNeoadjuvant chemotherapyNAC armTIL countClinical trialsImmune parametersNAC samplesBaseline PD-L1 expressionPathologic complete response rateDose-dense doxorubicinComplete response ratePD-L1 immunohistochemistryHER2-negative casesMinority of casesNab-paclitaxelResidual diseaseMean changeResponse rateLogistic regressionTILsBaselineEpithelial cellsHigh PCRChemotherapyTumors
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
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
2012
Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial
Shen K, Qi Y, Song N, Tian C, Rice SD, Gabrin MJ, Brower SL, Symmans WF, O’Shaughnessy J, Holmes FA, Asmar L, Pusztai L. Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial. BMC Medical Genomics 2012, 5: 51. PMID: 23158478, PMCID: PMC3536618, DOI: 10.1186/1755-8794-5-51.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveBreast NeoplasmsCell Line, TumorClinical Trials as TopicDemographyFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansMiddle AgedMultivariate AnalysisNeoadjuvant TherapyReproducibility of ResultsTreatment OutcomeUnited StatesConceptsMulti-gene predictorsBreast cancerNeoadjuvant chemotherapyCombination chemotherapyCyclophosphamide combination chemotherapyDocetaxel/capecitabineEpirubicin/cyclophosphamideER-negative patientsPathologic complete responseER-positive cancersReceiver-operating characteristic curveAU-ROCCell linesBlinded validation studyNeoadjuvant treatmentMost patientsComplete responseER statusPathologic responseClinical outcomesValidation studyResidual diseaseTx groupClinical trialsEstrogen receptor172O ER + /HER2+ and ER-/Her2+ Breast Cancers are Molecularly Distinct but Immune Gene Signatures are Prognostic and Predictive in Both Groups
Iwamoto T, Pusztai L, Matsuoka J, Callari M, Kelly C, Qi Y, Motoki T, Taira N, Santarpia L, Doihara H, Gianni L, Bianchini G. 172O ER + /HER2+ and ER-/Her2+ Breast Cancers are Molecularly Distinct but Immune Gene Signatures are Prognostic and Predictive in Both Groups. Annals Of Oncology 2012, 23: ix74-ix75. DOI: 10.1016/s0923-7534(20)32783-6.Peer-Reviewed Original ResearchPathologic complete responseER statusResidual diseaseER-/HER2HER2 cancersBetter prognosisBreast cancerHER2-positive breast cancerImmune gene signaturesSystemic adjuvant therapyPositive breast cancerEstrogen receptor statusHigher chemotherapy sensitivityDistinct molecular subtypesNeoadjuvant taxaneAdjuvant therapyImmune signaturesComplete responseReceptor statusHER2 patientsPoor prognosisMolecular subtypesChemotherapy sensitivityPredictive valueHER2
2010
Evaluation 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