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-upThe Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer
Dugo M, Huang C, Egle D, Bermejo B, Zamagni C, Seitz R, Nielsen T, Thill M, Antón-Torres A, Russo S, Ciruelos E, Schweitzer B, Ross D, Galbardi B, Greil R, Semiglazov V, Gyorffy B, Colleoni M, Kelly C, Mariani G, Del Mastro L, Blasi O, Callari M, Pusztai L, Valagussa P, Viale G, Gianni L, Bianchini G. The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39308141, PMCID: PMC11528202, DOI: 10.1158/1078-0432.ccr-24-0149.Peer-Reviewed Original ResearchPathologic complete response ratePathological complete responseTriple-negative breast cancerRNA-seqI-SPY2Immuno-oncologyBreast cancerPatients treated with pembrolizumabTumor-infiltrating lymphocyte countsPublicly available microarray dataPretreatment core biopsiesImmune checkpoint therapyRNA-seq dataPer-protocol populationAvailable microarray dataI-SPY2 trialPDL1 protein expressionNeoadjuvant atezolizumabNeoadjuvant immunotherapyPlus chemotherapyCheckpoint therapyComplete responseTriple-negativeCore biopsyRT-qPCR dataCorrelation of hormone receptor positive HER2-negative/MammaPrint high-2 breast cancer with triple negative breast cancer: Results from gene expression data from the ISPY2 trial.
Rios-Hoyo A, Xiong K, Marczyk M, García-Millán R, Wolf D, Huppert L, Nanda R, Yau C, Hirst G, van 't Veer L, Esserman L, Pusztai L. Correlation of hormone receptor positive HER2-negative/MammaPrint high-2 breast cancer with triple negative breast cancer: Results from gene expression data from the ISPY2 trial. Journal Of Clinical Oncology 2024, 42: 573-573. DOI: 10.1200/jco.2024.42.16_suppl.573.Peer-Reviewed Original ResearchGene expression dataGene expression analysisExpression dataExpressed genesExpression analysisTriple-negativeDistance analysisPathway analysisDifferential gene expression analysisCell cycle pathwayGene set enrichment analysisBreast cancerIngenuity Pathway AnalysisRate of pathological complete responseHigh-risk stage IIGlucocorticoid receptor signalingTriple negative breast cancerCycle pathwayPathological complete responseDNA repairEnrichment analysisOptimal treatment strategyNegative breast cancerI-SPY2 trialGenesIncidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial.
Nanda R, Cohen R, Quandt Z, Basu A, Yau C, Chien A, Pusztai L, Han H, Stringer-Reasor E, Isaacs C, Hershman D, Shatsky R, Perlmutter J, Yee D, DeMichele A, van 't Veer L, Hylton N, Esserman L, Rugo H. Incidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial. Journal Of Clinical Oncology 2024, 42: 584-584. DOI: 10.1200/jco.2024.42.16_suppl.584.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsEarly breast cancerIncidence of AIAdrenal insufficiencyI-SPY2Advanced diseaseBreast cancerRisk of immune-related adverse eventsHigh-risk early breast cancerImmune checkpoint inhibitor doseTriple-negative breast cancerAnti-LAG-3Approval of pembrolizumabEvaluate novel agentsICI-based therapyWeekly x 4Rate of adrenal insufficiencyPhase 2 trialI-SPY2 trialTime to onsetAge of ptsCheckpoint inhibitorsNeoadjuvant settingWeekly paclitaxel2LBA LBA Oral Immune subtyping in the Response Predictive Subtypes (RPS) identifies a subset of triple negative (TN) early-stage breast cancer patients with a very low likelihood of response to neoadjuvant immunotherapy (IO): results from 5 IO arms of the I-SPY2 TRIAL
Wolf D, Yau C, Haan J, Wehkamp D, Witteveen A, Glas A, Campbell M, Nanda R, Chien J, Shatsky R, Isaacs C, Barcura A, Mittempergher L, Kuilman M, Yee D, DeMichele A, Perlmutter J, Pusztai L, Esserman L, van ’t Veer L. 2LBA LBA Oral Immune subtyping in the Response Predictive Subtypes (RPS) identifies a subset of triple negative (TN) early-stage breast cancer patients with a very low likelihood of response to neoadjuvant immunotherapy (IO): results from 5 IO arms of the I-SPY2 TRIAL. European Journal Of Cancer 2024, 200: 113953. DOI: 10.1016/j.ejca.2024.113953.Peer-Reviewed Original Research
2023
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).
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 classifierI-SPY2Immune subtypingImmunotherapy armTherapy armAdverse eventsReceptor statusControl armDrug classesMast cellsLogistic regressionBenjamini-Hochberg methodHR subsetTumor cells
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 receptorsDiseaseTrialsTreatment 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
Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer
Symmans WF, Yau C, Chen YY, Balassanian R, Klein ME, Pusztai L, Nanda R, Parker BA, Datnow B, Krings G, Wei S, Feldman MD, Duan X, Chen B, Sattar H, Khazai L, Zeck JC, Sams S, Mhawech-Fauceglia P, Rendi M, Sahoo S, Ocal IT, Fan F, LeBeau LG, Vinh T, Troxell ML, Chien AJ, Wallace AM, Forero-Torres A, Ellis E, Albain KS, Murthy RK, Boughey JC, Liu MC, Haley BB, Elias AD, Clark AS, Kemmer K, Isaacs C, Lang JE, Han HS, Edmiston K, Viscusi RK, Northfelt DW, Khan QJ, Leyland-Jones B, Venters SJ, Shad S, Matthews JB, Asare SM, Buxton M, Asare AL, Rugo HS, Schwab RB, Helsten T, Hylton NM, van ’t Veer L, Perlmutter J, DeMichele AM, Yee D, Berry DA, Esserman LJ. Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer. JAMA Oncology 2021, 7: 1654-1663. PMID: 34529000, PMCID: PMC8446908, DOI: 10.1001/jamaoncol.2021.3690.Peer-Reviewed Original ResearchConceptsEvent-free survivalPathologic complete responseResidual cancer burdenInvestigational agentsInvestigational treatmentBreast cancerInterpretation of efficacyNeoadjuvant treatmentCancer burdenClinical trialsImproved event-free survivalNeoadjuvant breast cancer trialsStage 2/3 breast cancerHigh-risk breast cancerHormone receptorsI-SPY2 trialSecondary end pointsBreast cancer trialsEffective neoadjuvant treatmentI-SPY2Neoadjuvant paclitaxelNeoadjuvant trialsComplete responseEarly recurrencePrognostic significanceDurvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial
Pusztai L, Yau C, Wolf DM, Han HS, Du L, Wallace AM, String-Reasor E, Boughey JC, Chien AJ, Elias AD, Beckwith H, Nanda R, Albain KS, Clark AS, Kemmer K, Kalinsky K, Isaacs C, Thomas A, Shatsky R, Helsten TL, Forero-Torres A, Liu MC, Brown-Swigart L, Petricoin EF, Wulfkuhle JD, Asare SM, Wilson A, Singhrao R, Sit L, Hirst GL, Berry S, Sanil A, Asare AL, Matthews JB, Perlmutter J, Melisko M, Rugo HS, Schwab RB, Symmans WF, Yee D, Van't Veer LJ, Hylton NM, DeMichele AM, Berry DA, Esserman LJ. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Cancer Cell 2021, 39: 989-998.e5. PMID: 34143979, PMCID: PMC11064785, DOI: 10.1016/j.ccell.2021.05.009.Peer-Reviewed Original ResearchConceptsHER2-negative breast cancerTriple-negative breast cancerI-SPY2 trialBreast cancerNeoadjuvant chemotherapyStage II/III HER2-negative breast cancerStage II/III breast cancerGrade 3 adverse eventsPathologic complete response ratePD-L1 inhibitor durvalumabMast cell signaturePaclitaxel neoadjuvant chemotherapyComplete response rateHER2-negative patientsStandard neoadjuvant chemotherapyHER2-negative cancersPARP inhibitor olaparibAdverse eventsGene expression signaturesCare controlSuperior efficacyImmune responseResponse rateCancerInhibitor olaparibPredicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer before chemo-endocrine therapy
Du L, Yau C, Brown-Swigart L, Gould R, Krings G, Hirst G, Bedrosian I, Layman R, Carter J, Klein M, Venters S, Shad S, van der Noordaa M, Chien A, Haddad T, Isaacs C, Pusztai L, Albain K, Nanda R, Tripathy D, Liu M, Boughey J, Schwab R, Hylton N, DeMichele A, Perlmutter J, Yee D, Berry D, Veer L, Valero V, Esserman L, Symmans W. Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer before chemo-endocrine therapy. Annals Of Oncology 2021, 32: 642-651. PMID: 33617937, DOI: 10.1016/j.annonc.2021.02.011.Peer-Reviewed Original ResearchConceptsResidual cancer burdenI-SPY2 trialIndependent prognostic informationPrognostic informationBreast cancerPrognostic signaturePre-treatment tumor biopsiesHER2-negative breast cancerStage IIDistant relapse-free survivalMultivariate Cox regression modelHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Chemo-endocrine therapyEndocrine-based treatmentAdjuvant endocrine therapyGrowth factor receptor 2Primary outcome measureRelapse-free survivalSimilar prognostic informationCox regression modelMolecular prognostic signaturesNegative breast cancerFactor receptor 2MDACC cohort
2020
Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer
Consortium I, Yee D, DeMichele A, Yau C, Isaacs C, Symmans W, Albain K, Chen Y, Krings G, Wei S, Harada S, Datnow B, Fadare O, Klein M, Pambuccian S, Chen B, Adamson K, Sams S, Mhawech-Fauceglia P, Magliocco A, Feldman M, Rendi M, Sattar H, Zeck J, Ocal I, Tawfik O, LeBeau L, Sahoo S, Vinh T, Chien A, Forero-Torres A, Stringer-Reasor E, Wallace A, Pusztai L, Boughey J, Ellis E, Elias A, Lu J, Lang J, Han H, Clark A, Nanda R, Northfelt D, Khan Q, Viscusi R, Euhus D, Edmiston K, Chui S, Kemmer K, Park J, Liu M, Olopade O, Leyland-Jones B, Tripathy D, Moulder S, Rugo H, Schwab R, Lo S, Helsten T, Beckwith H, Haugen P, Hylton N, Veer L, Perlmutter J, Melisko M, Wilson A, Peterson G, Asare A, Buxton M, Paoloni M, Clennell J, Hirst G, Singhrao R, Steeg K, Matthews J, Asare S, Sanil A, Berry S, Esserman L, Berry D. Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer. JAMA Oncology 2020, 6: 1355-1362. PMID: 32701140, PMCID: PMC7378873, DOI: 10.1001/jamaoncol.2020.2535.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsBridged-Ring CompoundsCyclophosphamideDisease-Free SurvivalDoxorubicinFemaleHumansMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalProgression-Free SurvivalProportional Hazards ModelsReceptor, ErbB-2TaxoidsTrastuzumabTreatment OutcomeConceptsDistant recurrence-free survivalPathologic complete responseEvent-free survivalI-SPY2 trialRecurrence-free survivalLong-term outcomesBreast cancerComplete responseNeoadjuvant therapyPlatform trialsMolecular subtypesHigh-risk operable breast cancerThree-year event-free survivalHormone receptorsClinical stage 2Phase 3 confirmatory trialOperable breast cancerSubpopulation of womenNovel therapeutic combinationsStage 2Investigational regimensNeoadjuvant treatmentPrior surgeryTaxane treatmentStandard therapy
2013
Developing 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