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
2019
A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB)
Mayer IA, Prat A, Egle D, Blau S, Fidalgo JAP, Gnant M, Fasching PA, Colleoni M, Wolff AC, Winer EP, Singer CF, Hurvitz S, Estévez LG, van Dam PA, Kümmel S, Mundhenke C, Holmes F, Babbar N, Charbonnier L, Diaz-Padilla I, Vogl FD, Sellami D, Arteaga CL. A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB). Clinical Cancer Research 2019, 25: 2975-2987. PMID: 30723140, PMCID: PMC6522303, DOI: 10.1158/1078-0432.ccr-18-3160.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCell ProliferationClass I Phosphatidylinositol 3-KinasesFemaleHigh-Throughput Nucleotide SequencingHumansLetrozoleMiddle AgedMutationNeoadjuvant TherapyReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionThiazolesTreatment OutcomeConceptsObjective response rateMetastatic breast cancerBreast cancerResponse rateLetrozole treatmentPathologic complete response ratePhase II Randomized StudyHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorComplete response rateHormone receptor positiveMaculo-papular rashProgression-free survivalGrowth factor receptor 2Early breast cancerPhase I studiesWild-type cohortsFactor receptor 2Epidermal growth factor receptorCombination of alpelisibGrowth factor receptorNeoadjuvant letrozoleNeoadjuvant settingPrimary endpoint
2017
CDK4/6 inhibition triggers anti-tumour immunity
Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, Khan N, Ubellacker JM, Xie S, Metzger-Filho O, Hoog J, Ellis MJ, Ma CX, Ramm S, Krop IE, Winer EP, Roberts TM, Kim HJ, McAllister SS, Zhao JJ. CDK4/6 inhibition triggers anti-tumour immunity. Nature 2017, 548: 471-475. PMID: 28813415, PMCID: PMC5570667, DOI: 10.1038/nature23465.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationBiological MimicryBreast NeoplasmsCell Cycle CheckpointsCell Line, TumorCell ProliferationCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Disease Models, AnimalFemaleHumansInterferonsMicePhosphorylationProtein Kinase InhibitorsRepressor ProteinsRNA, Double-StrandedSignal TransductionT-Lymphocytes, RegulatoryTranscriptomeViruses
2016
The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis
Stover DG, Coloff JL, Barry WT, Brugge JS, Winer EP, Selfors LM. The Role of Proliferation in Determining Response to Neoadjuvant Chemotherapy in Breast Cancer: A Gene Expression–Based Meta-Analysis. Clinical Cancer Research 2016, 22: 6039-6050. PMID: 27330058, PMCID: PMC5161615, DOI: 10.1158/1078-0432.ccr-16-0471.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNeoadjuvant chemotherapyPathologic complete responseBreast cancerGene expression signaturesComplete responseExpression signaturesPrimary breast cancer biopsiesImmune activation signatureBreast cancer biopsiesRole of proliferationClinicopathologic characteristicsSignature scoreImmune activityCancer biopsiesPAM50 subtypesBreast tumorsProliferation differencesCancerActivation signatureNeoadjuvant chemosensitivityChemosensitivityTumorsDNA damageScoresTransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer
Jeselsohn R, Barry WT, Migliaccio I, Biagioni C, Zhao J, De Tribolet-Hardy J, Guarducci C, Bonechi M, Laing N, Winer EP, Brown M, Di Leo A, Malorni L. TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer. Clinical Cancer Research 2016, 22: 5755-5764. PMID: 27185372, PMCID: PMC5124409, DOI: 10.1158/1078-0432.ccr-16-0148.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalBreast NeoplasmsDisease-Free SurvivalDouble-Blind MethodEpidermal Growth FactorEstradiolFemaleFulvestrantGene Expression ProfilingHepatocyte Nuclear Factor 3-alphaHumansMiddle AgedPostmenopauseReceptors, EstrogenSignal TransductionTranscription Factor AP-2TranscriptomeConceptsProgression-free survivalBreast cancerPredictive biomarkersCONFIRM studyMetastatic estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerGene signatureBiologic pathwaysAdvanced breast cancerMetastatic breast cancerMultivariate Cox modelPotential new therapeutic targetEstrogen receptor antagonistNew therapeutic targetsNegative predictive valuePrimary tumor samplesNovel gene signatureMetastatic ERPrimary ERReceptor antagonistFulvestrant treatmentDecreased responseCox modelER levels
2015
Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discovery 2015, 5: 1164-1177. PMID: 26410082, PMCID: PMC4916970, DOI: 10.1158/2159-8290.cd-15-0369.Peer-Reviewed Original ResearchConceptsBrain metastasesPrimary tumorPrimary biopsiesRegional lymph node metastasisLymph node metastasisPI3K/Akt/mTORRegional lymph nodesPotential therapeutic targetPrimary tumor biopsiesPrimary tumor samplesAkt/mTORDistinct genetic alterationsWhole-exome sequencingExtracranial metastasesLymph nodesNode metastasisDismal prognosisActionable alterationsMetastasis sitesInformative alterationsIndividualized therapyTherapeutic targetMetastasisPrimary siteEGFR inhibitorsPI3K-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 activation
2012
TBCRC 001: Randomized Phase II Study of Cetuximab in Combination With Carboplatin in Stage IV Triple-Negative Breast Cancer
Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, Wolff AC, Hobday TJ, Ivanova A, Chiu WK, Ferraro M, Burrows E, Bernard PS, Hoadley KA, Perou CM, Winer EP. TBCRC 001: Randomized Phase II Study of Cetuximab in Combination With Carboplatin in Stage IV Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2012, 30: 2615-2623. PMID: 22665533, PMCID: PMC3413275, DOI: 10.1200/jco.2010.34.5579.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCarboplatinCetuximabDisease ProgressionFemaleHumansMiddle AgedNeoplasm StagingReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionSurvival AnalysisTreatment OutcomeConceptsTriple-negative breast cancerMetastatic triple-negative breast cancerOverall survivalResponse rateBreast cancerEpidermal growth factor receptorMost triple-negative breast cancersRandomized phase II trialBasal-like molecular subtypeBasal-like breast cancerEGFR pathwayArchival tissuePhase II studyPrimary end pointDays of therapyPhase II trialStrong preclinical dataEGFR antibody cetuximabFresh tumor tissueCombination cetuximabConcomitant therapyGrowth factor receptorCarboplatin regimenDisease stabilizationII trial
2004
New targets for therapy in breast cancer: Small molecule tyrosine kinase inhibitors
Lin NU, Winer EP. New targets for therapy in breast cancer: Small molecule tyrosine kinase inhibitors. Breast Cancer Research 2004, 6: 204. PMID: 15318926, PMCID: PMC549180, DOI: 10.1186/bcr919.Peer-Reviewed Original ResearchConceptsTyrosine kinase inhibitorsBreast cancerSmall molecule tyrosine kinase inhibitorsMolecule tyrosine kinase inhibitorsKinase inhibitorsErbB familyPredictive markerClinical dataReceptor signal transduction pathwaySmall molecule inhibitorsTumor sensitivityTumor growthReceptor tyrosine kinasesNew targetsCritical pathwaysMolecule inhibitorsCancerPotential crosstalkInhibitorsTyrosine kinaseSignal transduction pathwaysRational combinationBroad spectrumTransduction pathwaysMalignancy