2023
Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial.
Weiss A, Jin Q, Waks A, Yardley D, Spring L, Wrabel E, Tayob N, Viale G, Krop I, King T, Metzger-Filho O. Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial. Journal Of The American College Of Surgeons 2023, 238: 303-311. PMID: 38047578, DOI: 10.1097/xcs.0000000000000916.Peer-Reviewed Original ResearchHER2-positive breast cancerMulti-institution clinical trialBreast pCRBreast cancerDual HER2RCB-IIClinical trialsHigher pathologic complete response rateNodal responsePhase II single-arm trialPathologic complete response rateAxillary surgical stagingPathologic nodal responseResidual breast diseaseComplete response ratePre-operative treatmentSingle-arm trialPathologic nodal diseaseNeoadjuvant trialsYpN0 rateNodal diseaseSurgical stagingPathologic responseSystemic therapyFuture trials
2019
174O Predictive and prognostic value of B-cell gene-expression signatures and B-cell receptor (BCR) repertoire in HER2+ breast cancer: A correlative analysis of the CALGB 40601 clinical trial (Alliance)
Fernandez-Martinez A, Tanioka M, Fan C, Parker J, Hoadley K, Krop I, Partridge A, Carey L, Perou C. 174O Predictive and prognostic value of B-cell gene-expression signatures and B-cell receptor (BCR) repertoire in HER2+ breast cancer: A correlative analysis of the CALGB 40601 clinical trial (Alliance). Annals Of Oncology 2019, 30: v55. DOI: 10.1093/annonc/mdz240.Peer-Reviewed Original ResearchPathologic complete responseEvent-free survivalGene expression signaturesPrognostic valueBreast cancerCALGB 40601Clinical trialsSignature scoreImmune-mediated anti-tumor responseHigher pathologic complete responseTumor-infiltrating lymphocyte densityNeoadjuvant treatment strategiesAnti-tumor responseB cell signaturesB cell receptor repertoireExpression signaturesImmune-related signaturePre-treatment samplesDual HER2Neoadjuvant studiesCombination regimenComplete responseLymphocyte densityClinical parametersUnivariate analysis
2018
Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial
Powles RL, Redmond D, Sotiriou C, Loi S, Fumagalli D, Nuciforo P, Harbeck N, de Azambuja E, Sarp S, Di Cosimo S, Huober J, Baselga J, Piccart-Gebhart M, Elemento O, Pusztai L, Hatzis C. Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncology 2018, 4: e181564-e181564. PMID: 29902299, PMCID: PMC6224305, DOI: 10.1001/jamaoncol.2018.1564.Peer-Reviewed Original ResearchConceptsDual HER2 blockadeImmune gene signaturesPathologic complete responseDual HER2HER2 blockadeNeoALTTO trialDual anti-HER2 blockadeHigher immune gene expressionTrastuzumab Treatment Optimisation (ALTTO) trialHER2-positive breast cancerGene signatureAnti-HER2 blockadeHigher useHER2-positive patientsMultivariable logistic regressionRandomized clinical trialsGood responseHigh rateImmune gene expressionNeoadjuvant lapatinibTherapy armIdentifies patientsNeoadjuvant therapyComplete responseGene expression signatures
2015
Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib
Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. Journal Of Clinical Oncology 2015, 34: 542-549. PMID: 26527775, PMCID: PMC4980567, DOI: 10.1200/jco.2015.62.1268.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinomaEstrogen Receptor alphaFemaleGene ExpressionHumansImmunoglobulin GLapatinibMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualPaclitaxelQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRNA, MessengerTrastuzumabTreatment OutcomeTumor MicroenvironmentTumor Suppressor Protein p53Young AdultConceptsPathologic complete response rateCALGB 40601Dual therapyIntrinsic subtypesHormone receptor-negative diseaseRandomized phase III trialHuman epidermal growth factor receptor 2End pointHER2-positive breast cancerEpidermal growth factor receptor 2Correlative end pointsDual HER2 blockadeHER2-positive diseaseComplete response ratePrimary end pointPhase III trialsProgression-free survivalReceptor-negative diseaseAddition of lapatinibGrowth factor receptor 2Immune cell signaturesFactor receptor 2Gene expression-based assaysMolecular featuresDual HER2PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers
Wang Q, Liu P, Spangle JM, Von T, Roberts TM, Lin NU, Krop IE, Winer EP, Zhao JJ. PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers. Oncogene 2015, 35: 3607-3612. PMID: 26500061, PMCID: PMC4846581, DOI: 10.1038/onc.2015.406.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmFemaleHumansLapatinibMammary Neoplasms, ExperimentalMice, KnockoutMolecular Targeted TherapyPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseQuinazolinesReceptor, ErbB-2Signal TransductionThiazolesTumor BurdenXenograft Model Antitumor AssaysConceptsBreast tumorsP110β inhibitorsHuman epidermal growth factor receptor 2 (HER2) amplificationP110α inhibitionPTEN lossInhibition of HER2Treatment of HER2Human cancersPI3K pathway activationPTEN-deficient breast cancersGenetic mouse modelsPI3K/Akt signalingPTEN-deficient tumorsPI3K/AktDual HER2Therapeutic regimenHER2 inhibitionPIK3CA mutationsTumor regressionBreast cancerMouse modelXenograft modelHER2Null tumorsHER2 activationNeoadjuvant Dual HER2‐Targeted Therapy With Lapatinib and Trastuzumab Improves Pathologic Complete Response in Patients With Early Stage HER2‐Positive Breast Cancer: A Meta‐Analysis of Randomized Prospective Clinical Trials
Hicks M, Macrae E, Abdel‐Rasoul M, Layman R, Friedman S, Querry J, Lustberg M, Ramaswamy B, Mrozek E, Shapiro C, Wesolowski R. Neoadjuvant Dual HER2‐Targeted Therapy With Lapatinib and Trastuzumab Improves Pathologic Complete Response in Patients With Early Stage HER2‐Positive Breast Cancer: A Meta‐Analysis of Randomized Prospective Clinical Trials. The Oncologist 2015, 20: 337-343. PMID: 25732265, PMCID: PMC4391765, DOI: 10.1634/theoncologist.2014-0334.Peer-Reviewed Original ResearchConceptsAddition of lapatinibHER2-positive breast cancerNeoadjuvant chemotherapyBreast cancerLymph nodesClinical trialsEarly-stage HER2-positive breast cancerSan Antonio Breast Cancer SymposiumPathologic complete response rateEarly-stage breast cancerResidual invasive cancerResidual invasive carcinomaComplete response rateOperable breast cancerAxillary lymph nodesPathologic complete responseProspective clinical trialsStage breast cancerRates of pCRDual HER2NAC armProspective RCTsCancer SymposiumPCR rateComplete response
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