2023
Treatment 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 differencesChemotherapy
2022
Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm D, Pusztai L. Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC. Journal Of Clinical Oncology 2022, 40: 516-516. DOI: 10.1200/jco.2022.40.16_suppl.516.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerMultivariate logistic regression analysisPD-L1 statusLogistic regression analysisAA raceOverall survivalPathologic responseClinical trialsBreast cancerEarly-stage triple-negative breast cancerIncidence of irAEsPhase I/II trialPathologic complete response rateSignificant associationPhase I/II clinical trialsBaseline body mass indexSafety of immunotherapyWeekly nab-paclitaxelCharlson Comorbidity IndexComplete response ratePrimary efficacy endpointPD-L1 expressionBody mass indexBreast cancer recurrenceTreatment Efficacy Score—continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials
Marczyk M, Mrukwa A, Yau C, Wolf D, Chen Y, Balassanian R, Nanda R, Parker B, Krings G, Sattar H, Zeck J, Albain K, Boughey J, Liu M, Elias A, Clark A, Venters S, Shad S, Basu A, Asare S, Buxton M, Asare A, Rugo H, Perlmutter J, DeMichele A, Yee D, Berry D, Veer L, Symmans W, Esserman L, Pusztai L, Consortium I. Treatment Efficacy Score—continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials. Annals Of Oncology 2022, 33: 814-823. PMID: 35513244, DOI: 10.1016/j.annonc.2022.04.072.Peer-Reviewed Original ResearchConceptsTrial armsExperimental armSurvival differencesExact testPathologic complete response rateClinical trial armsI-SPY2 trialNeoadjuvant chemotherapy efficacyComplete response rateBreast cancer trialsCytotoxic efficacyFisher's exact testImpact of treatmentNeoadjuvant chemotherapyPCR ratePathologic responseResidual cancerControl cohortCancer trialsAssessed associationsChemotherapy efficacyEarly surrogateOlaparib armResponse rateHigher cytotoxic efficacy
2021
Comparison of Autologous Breast Reconstruction Complications by Type of Neoadjuvant Chemotherapy Regimen
Olawoyin OM, Mehta S, Chouairi F, Gabrick KS, Avraham T, Pusztai L, Alperovich M. Comparison of Autologous Breast Reconstruction Complications by Type of Neoadjuvant Chemotherapy Regimen. Plastic & Reconstructive Surgery 2021, 148: 1186-1196. PMID: 34644277, DOI: 10.1097/prs.0000000000008505.Peer-Reviewed Original ResearchConceptsNeoadjuvant chemotherapy regimensMicrovascular breast reconstructionNeoadjuvant chemotherapyChemotherapy regimensComplication rateFat necrosisBreast reconstructionImmune cellsCLINICAL QUESTION/LEVELMultivariate binary logistic regressionYale-New Haven HospitalAdministration of taxanesBreast Reconstruction ComplicationsInclusion of anthracyclinesNeoadjuvant chemotherapy regimenDosage of chemotherapyNew Haven HospitalNeoadjuvant chemotherapy completionLogistic regression modelsBinary logistic regressionOncologic historyTaxane administrationChemotherapy regimenChemotherapy completionPathologic response
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
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 samplesPatientsDeveloping Safety Criteria for Introducing New Agents into Neoadjuvant Trials
DeMichele A, Berry DA, Zujewski J, Hunsberger S, Rubinstein L, Tomaszewski JE, Kelloff G, Perlmutter J, Buxton M, Lyandres J, Albain KS, Benz C, Chien AJ, Haluska P, Leyland-Jones B, Liu MC, Munster P, Olopade O, Park JW, Parker BA, Pusztai L, Tripathy D, Rugo H, Yee D, Esserman L. Developing Safety Criteria for Introducing New Agents into Neoadjuvant Trials. Clinical Cancer Research 2013, 19: 2817-2823. PMID: 23470967, PMCID: PMC4096560, DOI: 10.1158/1078-0432.ccr-12-2620.Peer-Reviewed Original ResearchConceptsNeoadjuvant trialsNeoadjuvant settingStandard therapyInvestigational agentsDrug developmentPhase II neoadjuvant trialI-SPY2 trialSafe drug developmentShort-term endpointsNeoadjuvant studiesCurable patientsPathologic responsePoor prognosisNovel therapiesBreast cancerNovel agentsSafety dataStudy populationDisease processEfficacious drugsNew agentsDrug AdministrationPatient exposurePatient safetyStudy design
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 receptor
2011
Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer
Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, Denkert C, Eiermann W, Gnant M, Harris JR, Karn T, Liedtke C, Mauri D, Rouzier R, Ruckhaeberle E, Semiglazov V, Symmans WF, Tutt A, Pusztai L. Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer. Annals Of Surgical Oncology 2011, 19: 1508-1516. PMID: 22193884, DOI: 10.1245/s10434-011-2108-2.Peer-Reviewed Original ResearchConceptsNeoadjuvant systemic therapyPrimary breast cancerBreast cancerSystemic therapyBreast-conserving surgery rateLarge adjuvant trialsPathologic complete responseInflammatory breast cancerNew therapeutic regimensIntermediate end pointsInternational Consensus ConferenceClinical research groupAdjuvant trialsNew regimensPathologic responseComplete responseSurgery ratesTherapeutic regimensConsensus conferenceEnd pointTherapyCancerTrialsRegimensPanel of representativesA 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
Genomic Index of Sensitivity to Endocrine Therapy for Breast Cancer
Symmans WF, Hatzis C, Sotiriou C, Andre F, Peintinger F, Regitnig P, Daxenbichler G, Desmedt C, Domont J, Marth C, Delaloge S, Bauernhofer T, Valero V, Booser DJ, Hortobagyi GN, Pusztai L. Genomic Index of Sensitivity to Endocrine Therapy for Breast Cancer. Journal Of Clinical Oncology 2010, 28: 4111-4119. PMID: 20697068, PMCID: PMC2953969, DOI: 10.1200/jco.2010.28.4273.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalAromatase InhibitorsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantChi-Square DistributionDisease-Free SurvivalEstrogen Receptor alphaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenomicsHumansMiddle AgedNeoplasm StagingOligonucleotide Array Sequence AnalysisPatient SelectionProportional Hazards ModelsRisk AssessmentRisk FactorsSurvival AnalysisTamoxifenTime FactorsTranscription, GeneticTreatment OutcomeConceptsAdjuvant endocrine therapyEndocrine therapyBreast cancerDistant relapseER-positive breast cancerChemo-endocrine therapyDistant relapse riskYears of tamoxifenAdjuvant systemic therapyEstrogen receptor αBreast cancer samplesPrior chemotherapyNeoadjuvant chemotherapyPathologic responseSurvival benefitSystemic therapyUntreated cohortRelapse riskDeath riskTherapy indexAromatase inhibitionESR1 levelsReceptor αTamoxifenTherapy
2009
Clinical evaluation of chemotherapy response predictors developed from breast cancer cell lines
Liedtke C, Wang J, Tordai A, Symmans WF, Hortobagyi GN, Kiesel L, Hess K, Baggerly KA, Coombes KR, Pusztai L. Clinical evaluation of chemotherapy response predictors developed from breast cancer cell lines. Breast Cancer Research And Treatment 2009, 121: 301-309. PMID: 19603265, DOI: 10.1007/s10549-009-0445-7.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCell Line, TumorCyclophosphamideDoxorubicinDrug Resistance, NeoplasmFemaleFluorouracilGene Expression ProfilingHumansNeoplasm StagingOligonucleotide Array Sequence AnalysisPaclitaxelPredictive Value of TestsTreatment OutcomeConceptsBreast cancer cell linesCancer cell linesResponse predictorsBaseline gene expression dataCell linesChemotherapy drugsHuman breast cancer cell linesStandard chemotherapy drugsFine-needle aspiration specimensNeedle aspiration specimensPathologic responseAffymetrix U133A gene chipsClinical evaluationBreast cancerPharmacogenomic predictorsSame drugStage IPredictive valueAspiration specimensMultigene predictorsTumor samplesPatientsResistant cellsPatient dataDrugsPredictors of tumor progression during neoadjuvant chemotherapy in breast cancer
Caudle A, Gonzalez-Angulo A, Kelly H, Liu P, Pusztai L, Symmans W, Kuerer H, Mittendorf E, Hortobagyi G, Meric-Bernstam F. Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer. Journal Of Clinical Oncology 2009, 27: 603-603. DOI: 10.1200/jco.2009.27.15_suppl.603.Peer-Reviewed Original ResearchNeoadjuvant chemotherapyHigh Ki-67High tumor gradeStable diseasePR statusBreast cancerTumor gradeKi-67Negative ERNegative ER/PR statusFirst-line surgical approachSingle comprehensive cancer centerTumor progressionER/PR statusTaxane-based regimensComplete pathologic responseSubset of patientsLymph node metastasisHigher T stageComprehensive cancer centerPre-treatment characteristicsNCT regimenLymphovascular invasionMost patientsPathologic responseGenomic 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
Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab
Peintinger F, Buzdar AU, Kuerer HM, Mejia JA, Hatzis C, Gonzalez-Angulo AM, Pusztai L, Esteva FJ, Dawood SS, Green MC, Hortobagyi GN, Symmans WF. Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. Annals Of Oncology 2008, 19: 2020-2025. PMID: 18667396, PMCID: PMC2733116, DOI: 10.1093/annonc/mdn427.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials as TopicCyclophosphamideDoxorubicinEpirubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualNeoplasms, Hormone-DependentPaclitaxelRandomized Controlled Trials as TopicReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTrastuzumabConceptsHER2-positive breast cancerHormone receptor statusPathologic complete responseResidual cancer burdenPathologic responseBreast cancerNeoadjuvant chemotherapyReceptor statusExtensive residual diseaseHR-negative cancerHR-positive cancersPathologic response rateAddition of trastuzumabNeo-adjuvant chemotherapyStandard neoadjuvant chemotherapyFEC chemotherapyHR-/HER2Pathologic reviewComplete responseLymph nodesCancer burdenResidual diseasePrimary tumorChemotherapyResponse ratePreoperative Systemic Chemotherapy and Pathologic Assessment of Response
Pusztai L. Preoperative Systemic Chemotherapy and Pathologic Assessment of Response. Pathology & Oncology Research 2008, 14: 169-171. PMID: 18553157, DOI: 10.1007/s12253-008-9070-8.Peer-Reviewed Original ResearchConceptsPathologic complete responsePreoperative systemic chemotherapyResidual cancer burdenResidual diseaseNeoadjuvant treatmentSystemic chemotherapyAxillary nodal burdenNeoadjuvant clinical trialsRoutine therapeutic modalityAdvanced breast cancerPrimary tumor dimensionsTranslational research modelRoutine diagnostic practiceNodal burdenPathologic responseComplete responsePathologic assessmentPrognostic distinctionResistant diseaseCancer burdenAdverse outcomesTumor bedClinical trialsPathologic informationBreast cancerUse 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 Research
2007
Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy. Journal Of Clinical Oncology 2007, 25: 4414-4422. PMID: 17785706, DOI: 10.1200/jco.2007.10.6823.Peer-Reviewed Original ResearchConceptsDistant relapse-free survivalResidual cancer burdenHormone receptor statusNeoadjuvant chemotherapyHormone therapyPathologic responseReceptor statusCancer burdenResidual diseasePathologic American Joint CommitteeMultivariate Cox regression analysisAdjuvant hormone therapyBreast cancer burdenDifferent treatment cohortsPretreatment clinical stageAmerican Joint CommitteeCox regression analysisRelapse-free survivalSequential paclitaxelDistant relapseSame prognosisComplete responseNodal metastasisTreatment cohortsClinical stageThirty-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 scoreScoresCancer