2023
Prognostic and Predictive Value of Immune-Related Gene Expression Signatures vs Tumor-Infiltrating Lymphocytes in Early-Stage ERBB2/HER2-Positive Breast Cancer
Fernandez-Martinez A, Pascual T, Singh B, Nuciforo P, Rashid N, Ballman K, Campbell J, Hoadley K, Spears P, Pare L, Brasó-Maristany F, Chic N, Krop I, Partridge A, Cortés J, Llombart-Cussac A, Prat A, Perou C, Carey L. Prognostic and Predictive Value of Immune-Related Gene Expression Signatures vs Tumor-Infiltrating Lymphocytes in Early-Stage ERBB2/HER2-Positive Breast Cancer. JAMA Oncology 2023, 9: 490-499. PMID: 36602784, PMCID: PMC9857319, DOI: 10.1001/jamaoncol.2022.6288.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsFemaleGene Expression ProfilingHumansImmunoglobulin GLapatinibLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyPaclitaxelPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2TranscriptomeTrastuzumabTreatment OutcomeConceptsEvent-free survivalHER2-positive breast cancerPathologic complete responseERBB2/HER2-positive breast cancerPrimary end pointGene expression signaturesBreast cancerEnd pointImmune signaturesPretreatment tumorPrognostic valueExpression signaturesHigher pathologic complete responseMultivariable Cox modelSecondary end pointsAdditive prognostic valueTumor-Infiltrating LymphocytesIntrinsic tumor subtypesWeekly paclitaxelNeoadjuvant treatmentClinicopathologic factorsComplete responseCox analysisMedian ageImmune activation
2021
Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer
Keenan TE, Guerriero JL, Barroso-Sousa R, Li T, O’Meara T, Giobbie-Hurder A, Tayob N, Hu J, Severgnini M, Agudo J, Vaz-Luis I, Anderson L, Attaya V, Park J, Conway J, He MX, Reardon B, Shannon E, Wulf G, Spring LM, Jeselsohn R, Krop I, Lin NU, Partridge A, Winer EP, Mittendorf EA, Liu D, Van Allen EM, Tolaney SM. Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer. Nature Communications 2021, 12: 5563. PMID: 34548479, PMCID: PMC8455578, DOI: 10.1038/s41467-021-25769-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntigen PresentationAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBreast NeoplasmsCytokinesDrug Resistance, NeoplasmEstrogensFemaleFuransGene Expression ProfilingGenetic HeterogeneityGenome, HumanGenomicsHumansImmune Checkpoint InhibitorsKetonesLymphocytes, Tumor-InfiltratingMaleMiddle AgedMutationNeoplasm MetastasisReceptors, EstrogenReceptors, ProgesteroneSignal TransductionSurvival RateTreatment OutcomeConceptsImmune checkpoint inhibitorsBreast cancerHormone receptor-positive metastatic breast cancerHormone receptor-positive breast cancerFinal overall survival resultsRandomized phase 2 trialReceptor-positive breast cancerMinimal therapeutic effectPhase 2 trialMetastatic breast cancerOverall survival resultsPre-treatment tumorsCheckpoint inhibitorsCytokine changesICI responseCombination therapyImmune infiltrationImmunoregulatory cytokinesSurvival resultsAntigen presentationTherapeutic effectTherapeutic validationCancerMolecular correlatesTumor heterogeneity
2018
Integrated Analysis of RNA and DNA from the Phase III Trial CALGB 40601 Identifies Predictors of Response to Trastuzumab-Based Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer
Tanioka M, Fan C, Parker JS, Hoadley KA, Hu Z, Li Y, Hyslop TM, Pitcher BN, Soloway MG, Spears PA, Henry LN, Tolaney S, Dang CT, Krop IE, Harris LN, Berry DA, Mardis ER, Winer EP, Hudis CA, Carey LA, Perou CM. Integrated Analysis of RNA and DNA from the Phase III Trial CALGB 40601 Identifies Predictors of Response to Trastuzumab-Based Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer. Clinical Cancer Research 2018, 24: 5292-5304. PMID: 30037817, PMCID: PMC6214737, DOI: 10.1158/1078-0432.ccr-17-3431.Peer-Reviewed Original Research
2016
Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer
Varadan V, Gilmore H, Miskimen KL, Tuck D, Parsai S, Awadallah A, Krop IE, Winer EP, Bossuyt V, Somlo G, Abu-Khalaf MM, Fenton MA, Sikov W, Harris L. Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer. Clinical Cancer Research 2016, 22: 3249-3259. PMID: 26842237, PMCID: PMC5439498, DOI: 10.1158/1078-0432.ccr-15-2021.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminsAntineoplastic Agents, ImmunologicalBiomarkers, TumorB-LymphocytesBreast NeoplasmsFemaleGene Expression ProfilingHumansImmunity, InnateLymphocyte ActivationMacrophagesMiddle AgedNeoadjuvant TherapyPaclitaxelProgrammed Cell Death 1 ReceptorReceptor, ErbB-2T-Lymphocytes, Helper-InducerTrastuzumabTreatment OutcomeConceptsPathologic complete responseBreast cancerImmune indicesBrief exposureFollicular helper T (Tfh) cell signatureHER2-positive breast cancerPD-1 positivitySingle-agent trastuzumabTrastuzumab-based therapyT cell activityT-cell signatureImmune cell infiltrationTumor core biopsiesImmune cell activationPreoperative trastuzumabNab-paclitaxelAntitumor immunityImmune signaturesPCR rateComplete responseMulticenter trialPD-1Cell infiltrationCore biopsyIntrinsic subtypesCombination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases
Ni J, Ramkissoon SH, Xie S, Goel S, Stover DG, Guo H, Luu V, Marco E, Ramkissoon LA, Kang YJ, Hayashi M, Nguyen QD, Ligon AH, Du R, Claus EB, Alexander BM, Yuan GC, Wang ZC, Iglehart JD, Krop IE, Roberts TM, Winer EP, Lin NU, Ligon KL, Zhao JJ. Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases. Nature Medicine 2016, 22: 723-726. PMID: 27270588, PMCID: PMC4938731, DOI: 10.1038/nm.4120.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAminopyridinesAnimalsAntineoplastic AgentsApoptosisBrain NeoplasmsBreast NeoplasmsCarrier ProteinsCaspase 3Cell Cycle ProteinsDNA RepairDrug Resistance, NeoplasmDrug Therapy, CombinationEukaryotic Initiation FactorsEverolimusFemaleGene Expression ProfilingGenomic InstabilityHumansImmunohistochemistryKi-67 AntigenMagnetic Resonance ImagingMechanistic Target of Rapamycin Complex 1MiceMice, SCIDMolecular Targeted TherapyMorpholinesMultiprotein ComplexesNeoplasm TransplantationPhosphoinositide-3 Kinase InhibitorsPhosphoproteinsPhosphorylationReceptor, ErbB-2Remission InductionTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsBreast cancer brain metastasesCancer brain metastasesBrain metastasesHER2-positive breast cancer brain metastasesOrthotopic patient-derived xenograftsPI3KPatient-derived xenograftsDurable remissionsTherapeutic responseMouse modelCombined inhibitionCombination inhibitionMetastasisInhibitionRemissionXenograftsMice
2002
Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression)
Seth P, Krop I, Porter D, Polyak K. Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression). Oncogene 2002, 21: 836-843. PMID: 11850811, DOI: 10.1038/sj.onc.1205113.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBreast NeoplasmsDioxygenasesEstrogen AntagonistsEstrogensFemaleGene Expression ProfilingHypoxia-Inducible Factor-Proline DioxygenasesIn Situ HybridizationMolecular Sequence DataNuclear ProteinsOligonucleotide Array Sequence AnalysisPhylogenyProcollagen-Proline DioxygenaseReceptors, EstrogenRNA, NeoplasmSequence Homology, Amino AcidTamoxifenTranscriptional ActivationTumor Cells, CulturedConceptsNovel nuclear proteinLigand-dependent transcription factorsDirect transcriptional targetGene expression profilesImmediate early genesTranscriptional targetsTranscription factorsEstrogen-dependent breast cancer cell linesNuclear proteinsSAGE technologyExpression profilesConstitutive expressionHuman breast cancer cellsBreast cancer cellsGenesBreast cancer cell linesCell growthCancer cell linesInitial characterizationNew memberColony growthCancer cellsCell linesNovel estrogenEstrogen receptor
2001
A SAGE (serial analysis of gene expression) view of breast tumor progression.
Porter DA, Krop IE, Nasser S, Sgroi D, Kaelin CM, Marks JR, Riggins G, Polyak K. A SAGE (serial analysis of gene expression) view of breast tumor progression. Cancer Research 2001, 61: 5697-702. PMID: 11479200.Peer-Reviewed Original ResearchConceptsGene expression profilesMammary epithelial cellsNormal mammary epithelial cellsExpression profilesGlobal gene expression profilesDistinct gene expression patternsSet of genesGene expression patternsConsistent phenotypic changesBreast tumorigenesisCarcinoma transitionEpithelial cellsSecreted proteinsSAGE librariesExpression patternsGene expressionPhenotypic changesGenesBreast tumor progressionMolecular levelSerial analysisSpecific stagesMammary epitheliumTumor progressionPromising targetHIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells
Krop I, Sgroi D, Porter D, Lunetta K, LeVangie R, Seth P, Kaelin C, Rhei E, Bosenberg M, Schnitt S, Marks J, Pagon Z, Belina D, Razumovic J, Polyak K. HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 9796-9801. PMID: 11481438, PMCID: PMC55532, DOI: 10.1073/pnas.171138398.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBlotting, NorthernBlotting, WesternBreastBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingCarcinoma, LobularCell DivisionCells, CulturedChlorocebus aethiopsCHO CellsCOS CellsCricetinaeCricetulusCytokinesDNA MethylationEpithelial CellsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene LibraryGene SilencingGenes, Tumor SuppressorGrowth InhibitorsHumansMolecular Sequence DataNeoplasm ProteinsPromoter Regions, GeneticRecombinant Fusion ProteinsRNA, MessengerRNA, NeoplasmSequence AlignmentSequence Homology, Amino AcidTransfectionTumor Cells, CulturedTumor Suppressor ProteinsConceptsHIN-1 expressionHIN-1Mammary epithelial cellsPutative cytokineEpithelial cellsBreast cancer cell linesHuman breast carcinomaCancerous mammary epithelial cellsBreast cancer cellsCancer cell linesDuctal carcinomaLobular carcinomaPrimary tumorPreinvasive lesionsBreast carcinomaCandidate tumor suppressor geneMolecular alterationsTumor suppressor geneCarcinomaCancer cellsGene expression profilesCell linesCytokinesSuppressor geneCell growth