2024
Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial
Rediti M, Venet D, Joaquin Garcia A, Maetens M, Vincent D, Majjaj S, El-Abed S, Di Cosimo S, Ueno T, Izquierdo M, Piccart M, Pusztai L, Loi S, Salgado R, Viale G, Rothé F, Sotiriou C. Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial. Nature Communications 2024, 15: 10402. PMID: 39613746, PMCID: PMC11607438, DOI: 10.1038/s41467-024-54621-3.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase III as TopicFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedNeoplasm Recurrence, LocalPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2TrastuzumabTumor MicroenvironmentConceptsHER2-positive breast cancerMolecular subtypesBreast cancerRate of pathological complete responseSensitive to HER2-targeted therapiesClinical trialsRisk of distant recurrenceBreast cancer molecular subtypesPathological complete responseHER2-targeted therapyCancer molecular subtypesPotential clinical implicationsNeoALTTO trialDistant recurrenceComplete responseAdjuvant trastuzumabPrognostic/predictive valueHeterogeneous biologySurvival outcomesI-SPY2Clinical outcomesMicroenvironment featuresGene expression profilesExternal cohortTumorHormone Receptor Positive HER2-negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple Negative Breast Cancers.
Rios-Hoyo A, Xiong K, Dai J, Yau C, Marczyk M, Garcia-Milian R, Wolf D, Huppert L, Nanda R, Hirst G, Cobain E, van 't Veer L, Esserman L, Pusztai L. Hormone Receptor Positive HER2-negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple Negative Breast Cancers. Clinical Cancer Research 2024 PMID: 39561272, DOI: 10.1158/1078-0432.ccr-24-1553.Peer-Reviewed Original ResearchPathological complete responseEvent-free survivalBreast cancerHER2 negative breast cancerHormone receptor-positive/HER2-negativePathologic complete response ratePrognostic risk categoriesTN breast cancerNegative breast cancerGene set analysisExpression of cell cycleGene expression dataLow-risk subgroupsHigh-risk groupMammaPrint assayNeoadjuvant trialsComplete responseER statusResidual cancerPrognostic groupsClinical featuresI-SPY2Prognostic assaysExpression dataTreatment strategiesPathologic 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 dataIncidence 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 ResearchNeoadjuvant 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
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 armsBiomarkers 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 cells
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 significanceGanitumab 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