2024
Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer.
Chavez-MacGregor M, Miao J, Pusztai L, Goetz M, Rastogi P, Ganz P, Mamounas E, Paik S, Bandos H, Razaq W, O'Dea A, Kaklamani V, Silber A, Flaum L, Andreopoulou E, Wendt A, Carney J, Sharma P, Gralow J, Lew D, Barlow W, Hortobagyi G. Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer. Journal Of Clinical Oncology 2024, jco2302344. PMID: 38833643, DOI: 10.1200/jco.23.02344.Peer-Reviewed Original ResearchInvasive disease-free survivalHormone receptor-positiveEndocrine therapyOverall survivalBreast cancerHazard ratioReceptor-positiveHigh riskSubset analysisHormone receptor-positive metastatic breast cancerRisk groupsHormone receptor-positive BCEarly-stage breast cancerStratified log-rank testProgression-free survivalEfficacy of everolimusDisease-free survivalMetastatic breast cancerPlacebo-controlled trialSecondary end pointsLog-rank testHighest grade 3Treatment completion ratesPhase IIIEverolimus armPre-treatment amino acids and risk of paclitaxel-induced peripheral neuropathy in SWOG S0221
Chen C, Zirpoli G, Budd G, Barlow W, Pusztai L, Hortobagyi G, Albain K, Godwin A, Thompson A, Henry N, Ambrosone C, Stringer K, Hertz D. Pre-treatment amino acids and risk of paclitaxel-induced peripheral neuropathy in SWOG S0221. Cancer Chemotherapy And Pharmacology 2024, 1-11. PMID: 38814343, DOI: 10.1007/s00280-024-04680-6.Peer-Reviewed Original ResearchCIPN severityPeripheral neuropathyPaclitaxel-induced peripheral neuropathyEarly-stage breast cancerTrial of patientsBackgroundChemotherapy-induced peripheral neuropathyBody mass indexSerum amino acid concentrationsOver-representation analysisDebilitating neurotoxicityPaclitaxel scheduleAnti-cancer agentsBreast cancerSelf-reported raceMass indexMetabolic pathways of amino acidsSerum concentrationsInverse associationAmino acid metabolic pathwaysPaclitaxelPrimary analysisBonferroni correctionTreatment limitationsS0221CIPNElucidating the immune active state of HR+HER2- MammaPrint High 2 early breast cancer.
Cobain E, Pusztai L, Graham C, Whitworth P, Beitsch P, Osborne C, Layeequr Rahman R, Johnson N, Brufsky A, Mahtani R, Gadi V, Hoskins K, Linden H, Mukhtar R, Esserman L, Haan J, Quinn K, Menicucci A, Audeh M, O'Shaughnessy J. Elucidating the immune active state of HR+HER2- MammaPrint High 2 early breast cancer. Journal Of Clinical Oncology 2024, 42: 506-506. DOI: 10.1200/jco.2024.42.16_suppl.506.Peer-Reviewed Original ResearchEarly-stage breast cancerAntigen presenting cellsImmune cell frequenciesImmune activation stateT cellsAntigen presentationB cellsBreast cancerResponse rate to neoadjuvant chemotherapyCell frequencyRate to neoadjuvant chemotherapyResponse rates to immunotherapyRisk of distant recurrenceCD4+ memory T cellsHigh-risk early-stage breast cancerCD8+ T cellsAntigen processingI-SPY 2Major histocompatibilityTumor-infiltrating lymphocytesMemory T cellsIncreased antigen presentationMemory B cellsActivated dendritic cellsImmune therapy responseNeoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.
Albain K, Yau C, Petricoin E, Wolf D, Lang J, Chien A, Haddad T, Forero-Torres A, Wallace A, Kaplan H, Pusztai L, Euhus D, Nanda R, Elias A, Clark A, Godellas C, Boughey J, Isaacs C, Tripathy D, Lu J, Yung R, Gallagher R, Wulfkuhle J, Brown-Swigart L, Krings G, Chen Y, Potter D, Stringer-Reasor E, Blair S, Asare S, Wilson A, Hirst G, Singhrao R, Buxton M, Clennell J, Sanil A, Berry S, Asare A, Matthews J, DeMichele A, Hylton N, Melisko M, Perlmutter J, Rugo H, Symmans W, Van't Veer L, Yee D, Berry D, Esserman L. Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery. Clinical Cancer Research 2024, 30: 729-740. PMID: 38109213, PMCID: PMC10956403, DOI: 10.1158/1078-0432.ccr-22-2256.Peer-Reviewed Original ResearchPathological complete responseI-SPY2Breast cancerStage II/III breast cancerPhase II neoadjuvant trialTie2 receptorEarly-stage breast cancerT-cell gene signatureHormone receptorsDoxorubicin/cyclophosphamideHER2-negative diseaseHER2-positive diseaseStandard neoadjuvant therapyEvent-free survivalPhase III trialsPaclitaxel-based chemotherapyBreast cancer trialsPathway-specific biomarkersCell gene signatureNeoadjuvant trialsWeekly paclitaxelNeoadjuvant therapyPrimary endpointIII trialsPCR rate
2023
Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221.
Chen C, Zirpoli G, Barlow W, Budd G, McKiver B, Pusztai L, Hortobagyi G, Albain K, Damaj M, Godwin A, Thompson A, Henry N, Ambrosone C, Stringer K, Hertz D. Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221. Journal Of The National Comprehensive Cancer Network 2023, 21: 1172-1180.e3. PMID: 37935109, PMCID: PMC10976748, DOI: 10.6004/jnccn.2023.7062.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyVitamin D insufficiencyD insufficiencyVitamin DPaclitaxel scheduleMechanical hypersensitivityPeripheral neuropathyRisk factorsDeficient dietPaclitaxel-Induced Peripheral NeuropathyEarly-stage breast cancerPaclitaxel-containing chemotherapyVitamin D supplementationSufficient vitamin DVitamin D deficiencyBody mass indexMultiple logistic regressionSelf-reported raceD supplementationD deficiencySensitized miceProspective trialFemale patientsMass indexPredictive biomarkersIntratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer
Kahn A, Golestani R, Harigopal M, Pusztai L. Intratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer. Breast Cancer Research And Treatment 2023, 201: 289-298. PMID: 37378695, DOI: 10.1007/s10549-023-06977-1.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPD-L1 expressionBreast cancerPD-L1Metastatic triple-negative breast cancerPD-L1 positive casesEarly-stage breast cancerPD-L1 protein expressionImmune checkpoint inhibitorsPD-L1 positivityPD-L1 statusProtein expressionWhole study populationPrimary breast tumorsNegative breast cancerConcordant negative resultsCheckpoint inhibitorsMultiple biopsiesPositive cancersCohen's kappa coefficientStudy populationE1L3N antibodyDiscordance rateBreast tumorsPositive casesOncotype DX results increase concordance in adjuvant chemotherapy recommendations for early-stage breast cancer
Licata L, Viale G, Giuliano M, Curigliano G, Chavez-MacGregor M, Foldi J, Oke O, Collins J, Del Mastro L, Puglisi F, Montemurro F, Vernieri C, Gerratana L, Giordano S, Rognone A, Sica L, Gentilini O, Cascinu S, Pusztai L, Giordano A, Criscitiello C, Bianchini G. Oncotype DX results increase concordance in adjuvant chemotherapy recommendations for early-stage breast cancer. Npj Breast Cancer 2023, 9: 51. PMID: 37291235, PMCID: PMC10250312, DOI: 10.1038/s41523-023-00559-6.Peer-Reviewed Original ResearchEarly-stage breast cancerAdjuvant chemotherapy recommendationsChemotherapy recommendationsOncotype DX resultsClinicopathologic featuresRecurrence scorePhysician uncertaintyBreast cancerDiscordant recommendationsAdjuvant chemotherapy resultsAddition of chemotherapyChemotherapy resultsOncotype DXInstitutional databasePhysician judgmentBreast oncologistsClinical practiceOncologistsCancerAssay resultsRS resultsChange recommendationsPredictive informationChemotherapyRecommendationsBiomarkers predicting response to 5 immunotherapy arms in the neoadjuvant I-SPY2 trial for early-stage breast cancer (BC): Evaluation of immune subtyping in the response predictive subtypes (RPS).
Wolf D, Yau C, Campbell M, Glas A, Mittempergher L, Kuilman M, Barcaru A, Brown Swigart L, Nanda R, Chien A, Pusztai L, Stringer-Reasor E, Shatsky R, Isaacs C, Perlmutter J, DeMichele A, Yee D, Esserman L, van 't Veer L. Biomarkers predicting response to 5 immunotherapy arms in the neoadjuvant I-SPY2 trial for early-stage breast cancer (BC): Evaluation of immune subtyping in the response predictive subtypes (RPS). Journal Of Clinical Oncology 2023, 41: 102-102. DOI: 10.1200/jco.2023.41.16_suppl.102.Peer-Reviewed Original ResearchPCR rateBreast cancerImmune markersSerious immune-related adverse eventsImmune-related adverse eventsHER2-negative breast cancerEarly-stage breast cancerI-SPY2 trialLower mast cellTumor immune signatureChemokines/cytokinesSingle-sample classifierImmune subtypingImmunotherapy armI-SPY2Therapy armAdverse eventsReceptor statusControl armDrug classesMast cellsLogistic regressionBenjamini-Hochberg methodHR subsetTumor cellsHRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC).
Jeon J, Chen K, Madison R, Schrock A, Sokol E, Levy M, Oxnard G, Huang R, Pusztai L. HRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC). Journal Of Clinical Oncology 2023, 41: 539-539. DOI: 10.1200/jco.2023.41.16_suppl.539.Peer-Reviewed Original ResearchEarly-stage breast cancerPrimary breast cancerEarly breast cancerBreast cancerStage IHR-/HER2HRR deficiencyPALB2 mutationsEarly-stage primary breast cancerPARP inhibitorsStage IV diseaseHormone receptor statusMonths of diagnosisPositive breast cancerHomologous recombination repairComprehensive genomic profilingHRD signaturesClinical trial dataHigh rateSEER studySomatic BRCAAdjuvant therapyAdvanced diseaseReceptor statusBC subtypesP111 A phase 3, open-label trial of neoadjuvant trastuzumab deruxtecan (T-DXd) monotherapy or T-DXd followed by THP vs ddAC-THP in high-risk HER2-positive early-stage breast cancer (DESTINY-Breast11)
Harbeck N, Boileau J, Modi S, Kelly C, Ohno S, Wu J, Konpa A, Herbolsheimer P, Safdar S, Zhang Y, Pusztai L. P111 A phase 3, open-label trial of neoadjuvant trastuzumab deruxtecan (T-DXd) monotherapy or T-DXd followed by THP vs ddAC-THP in high-risk HER2-positive early-stage breast cancer (DESTINY-Breast11). The Breast 2023, 68: s57. DOI: 10.1016/s0960-9776(23)00228-x.Peer-Reviewed Original Research
2022
Treatment Sequencing Patterns and Associated Direct Medical Costs of Metastatic Breast Cancer Care in the United States, 2011 to 2021
Chehayeb R, Hood A, Wang X, Miksad R, Mougalian S, Lustberg M, Wang S, Greenup R, Pusztai L, Kunst N. Treatment Sequencing Patterns and Associated Direct Medical Costs of Metastatic Breast Cancer Care in the United States, 2011 to 2021. JAMA Network Open 2022, 5: e2244204. PMID: 36445704, PMCID: PMC9709649, DOI: 10.1001/jamanetworkopen.2022.44204.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerErbB2-positive metastatic breast cancerHR-positive metastatic breast cancerLines of therapyMBC subtypesDrug costsBreast cancerMedical costsHuman epidermal growth factor receptor 2 receptor statusMBC treatmentERBB2-negative metastatic breast cancerAssociated direct medical costsEarly-stage breast cancerHormone receptorsFlatiron Health databaseMetastatic recurrence ratesDifferent drug regimensBreast cancer careData of patientsDirect medical costsNovel adjuvant therapySupportive care drugsOutcomes of interestCost-effectiveness analysisAdjuvant therapyVitamin D insufficiency as a peripheral neuropathy risk factor in white and black patients in SWOG 0221.
Chen C, Zirpoli G, McCann S, Barlow W, Budd G, Pusztai L, Hortobagyi G, Godwin A, Thompson A, Ambrosone C, Stringer K, Hertz D. Vitamin D insufficiency as a peripheral neuropathy risk factor in white and black patients in SWOG 0221. Journal Of Clinical Oncology 2022, 40: 12023-12023. DOI: 10.1200/jco.2022.40.16_suppl.12023.Peer-Reviewed Original ResearchVitamin D insufficiencyPaclitaxel-induced peripheral neuropathyD insufficiencyPeripheral neuropathyBlack patientsPaclitaxel scheduleIncrease riskHigh riskEarly-stage breast cancerNeuropathy risk factorsPaclitaxel-containing chemotherapyVitamin D supplementationSensory peripheral neuropathyTreatment-limiting toxicityBody mass indexRetrospective validation studySelf-reported raceD supplementationProspective trialWhite patientsFemale patientsMass indexBlack raceRisk factorsTreatment outcomesBiomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update
Andre F, Ismaila N, Allison KH, Barlow WE, Collyar DE, Damodaran S, Henry NL, Jhaveri K, Kalinsky K, Kuderer NM, Litvak A, Mayer EL, Pusztai L, Raab R, Wolff AC, Stearns V. Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update. Journal Of Clinical Oncology 2022, 40: 1816-1837. PMID: 35439025, DOI: 10.1200/jco.22.00069.Peer-Reviewed Original ResearchConceptsBreast Cancer IndexEarly-stage breast cancerHER2- breast cancerAdjuvant endocrinePositive nodesBreast cancerEndocrine therapyPostmenopausal patientsPremenopausal patientsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Early-stage estrogen receptorTriple-negative breast cancerAdjuvant therapy decisionsASCO Guideline UpdateExtended endocrine therapyProspective-retrospective studyEvidence of recurrenceGrowth factor receptor 2Recurrence-free survivalGenomic testsNegative breast cancerEvidence-based recommendationsFactor receptor 2Outcomes of interest
2021
Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial.
Venet D, Rediti M, Maetens M, Fumagalli D, Brown DN, Majjaj S, Salgado R, Pusztai L, Harbeck N, El-Abed S, Wang Y, Saura C, Gomez H, Semiglazov VF, de Azambuja E, Huober J, Nuciforo P, Di Cosimo S, Piccart M, Loi S, Rothé F, Sotiriou C. Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial. Clinical Cancer Research 2021, 27: clincanres.1317.2021. PMID: 34321278, DOI: 10.1158/1078-0432.ccr-21-1317.Peer-Reviewed Original ResearchConceptsPathologic complete responseNeoALTTO trialCopy number aberrationsBreast cancerHER2-positive early-stage breast cancerEstrogen receptor-positive subgroupNeoadjuvant anti-HER2 therapyEarly-stage breast cancerHER2-positive breast cancerPhase III clinical trialsAnti-HER2 therapyAnti-HER2 agentsPredictors of responseReceptor-positive subgroupNumber aberration analysisCopy number levelsWarrants further investigationHeterogeneity of responseComplete responseSurvival outcomesWhole cohortClinical trialsImmune processesPatientsSignificant associationOptimal Management for Residual Disease Following Neoadjuvant Systemic Therapy
Foldi J, Rozenblit M, Park TS, Knowlton CA, Golshan M, Moran M, Pusztai L. Optimal Management for Residual Disease Following Neoadjuvant Systemic Therapy. Current Treatment Options In Oncology 2021, 22: 79. PMID: 34213636, DOI: 10.1007/s11864-021-00879-4.Peer-Reviewed Original ResearchConceptsPathologic complete responseResidual cancerClinical trialsAdjuvant therapyExcellent long-term disease-free survivalLong-term disease-free survivalAxillary lymph node dissectionHuman epidermal growth factor receptor 2Early-stage breast cancerEpidermal growth factor receptor 2Post-mastectomy breastSystemic adjuvant therapyInternal mammary nodesLymph node dissectionNeoadjuvant systemic therapyDisease-free survivalGrowth factor receptor 2Minimal residual disease monitoringRecurrence-free survivalType of surgeryPivotal clinical trialsOngoing clinical trialsFactor receptor 2Residual disease monitoringAccurate prognostic estimatesNeoadjuvant endocrine therapy use in early stage breast cancer during the covid-19 pandemic
Park KU, Gregory M, Bazan J, Lustberg M, Rosenberg S, Blinder V, Sharma P, Pusztai L, Shen C, Partridge A, Thompson A. Neoadjuvant endocrine therapy use in early stage breast cancer during the covid-19 pandemic. Breast Cancer Research And Treatment 2021, 188: 249-258. PMID: 33651271, PMCID: PMC7921279, DOI: 10.1007/s10549-021-06153-3.Peer-Reviewed Original ResearchConceptsAxillary lymph node dissectionNeoadjuvant endocrine therapyMedical oncologistsRadiation oncologistsOmission of ALNDEstrogen positive breast cancer patientsPositive breast cancer patientsEarly-stage breast cancerEndocrine therapy useMetastatic axillary diseaseLymph node dissectionBreast cancer patientsMultidisciplinary tumor boardStage breast cancerClinical trial organizationsPercent of practicesUS medical oncologistsCOVID-19 pandemicPre-pandemic timesRegional COVID-19 casesAxillary diseaseMicrometastatic nodesSurgery 2Endocrine therapyLocoregional management
2020
Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer
Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van ‘t Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer. JAMA Oncology 2020, 6: 676-684. PMID: 32053137, PMCID: PMC7058271, DOI: 10.1001/jamaoncol.2019.6650.Peer-Reviewed Original ResearchConceptsEarly-stage breast cancerPathologic complete responseNeoadjuvant chemotherapyPhase 3 trialResidual cancer burdenStandard neoadjuvant chemotherapyBreast cancerComplete responseInvestigational armStage II/III breast cancerHigher event-free survival rateERBB2-negative breast cancerEvent-free survival rateAnthracycline-based neoadjuvant chemotherapyDistant recurrence-free survivalEnd pointTriple-negative breast cancerCycles of pembrolizumabEffect of pembrolizumabImmune-related endocrinopathiesNeoadjuvant clinical trialsTriple-negative cohortPrimary end pointSecondary end pointsRecurrence-free survivalGene 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
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 sequencing
2018
Comparison of Residual Risk–Based Eligibility vs Tumor Size and Nodal Status for Power Estimates in Adjuvant Trials of Breast Cancer Therapies
Wei W, Kurita T, Hess KR, Sanft T, Szekely B, Hatzis C, Pusztai L. Comparison of Residual Risk–Based Eligibility vs Tumor Size and Nodal Status for Power Estimates in Adjuvant Trials of Breast Cancer Therapies. JAMA Oncology 2018, 4: e175092-e175092. PMID: 29372234, PMCID: PMC5885272, DOI: 10.1001/jamaoncol.2017.5092.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantEligibility DeterminationFemaleHumansLymph NodesLymphatic MetastasisMiddle AgedNeoplasm Recurrence, LocalNeoplasm, ResidualPatient SelectionPrognosisRandomized Controlled Trials as TopicReproducibility of ResultsResearch DesignRetrospective StudiesRisk FactorsSurvival AnalysisTrastuzumabTumor BurdenWatchful WaitingYoung AdultConceptsTumor sizeAdjuvant trialsEligibility criteriaNodal statusClinical trialsResidual riskEarly-stage breast cancerAdjuvant clinical trialsBaseline prognostic riskFuture adjuvant trialsResidual risk estimatesRisk of recurrenceBreast cancer therapyRisk thresholdTrial powerClinical trial powerTrial eligibilityAdjuvant therapyCare therapyConsecutive patientsPrognostic riskPatient eligibilityTrial populationPatient cohortControl arm