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 heterogeneityGenomic features of rapid versus late relapse in triple negative breast cancer
Zhang Y, Asad S, Weber Z, Tallman D, Nock W, Wyse M, Bey JF, Dean KL, Adams EJ, Stockard S, Singh J, Winer EP, Lin NU, Jiang YZ, Ma D, Wang P, Shi L, Huang W, Shao ZM, Cherian M, Lustberg MB, Ramaswamy B, Sardesai S, VanDeusen J, Williams N, Wesolowski R, Obeng-Gyasi S, Sizemore GM, Sizemore ST, Verschraegen C, Stover DG. Genomic features of rapid versus late relapse in triple negative breast cancer. BMC Cancer 2021, 21: 568. PMID: 34006255, PMCID: PMC8130400, DOI: 10.1186/s12885-021-08320-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorChemotherapy, AdjuvantDatasets as TopicDisease-Free SurvivalDNA Copy Number VariationsFemaleFollow-Up StudiesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLogistic ModelsMastectomyMiddle AgedModels, GeneticMutationNeoadjuvant TherapyNeoplasm Recurrence, LocalPrognosisRisk AssessmentTime FactorsTriple Negative Breast NeoplasmsConceptsLate relapseRapid relapseImmune signaturesBreast cancerAnti-tumor CD8 T cellsBackgroundTriple-negative breast cancerTriple-negative breast cancerCD8 T cellsTumor mutation burdenIndependent validation cohortNegative breast cancerFisher's exact testPearson's chi-squared testChi-squared testLogistic regression modelsLuminal signaturePrimary TNBCTNBC subsetImmune subsetsClinical featuresValidation cohortWhole-genome copy numberPrimary tumorM1 macrophagesT cells
2020
Oncotype DX testing in node-positive breast cancer strongly impacts chemotherapy use at a comprehensive cancer center
Losk K, Freedman RA, Laws A, Kantor O, Mittendorf EA, Tan-Wasielewski Z, Trippa L, Lin NU, Winer EP, King TA. Oncotype DX testing in node-positive breast cancer strongly impacts chemotherapy use at a comprehensive cancer center. Breast Cancer Research And Treatment 2020, 185: 215-227. PMID: 32939592, DOI: 10.1007/s10549-020-05931-9.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsChemotherapy, AdjuvantFemaleGene Expression ProfilingHumansNeoplasm Recurrence, LocalReceptors, EstrogenRiskConceptsRecurrence-free survivalPN1 breast cancerRecurrence scoreChemotherapy useBreast cancerOverall survivalChemotherapy receiptPN1 patientsRS testingUse of RSNode-positive breast cancerOncotype DX recurrence scoreAdjuvant chemotherapy receiptLow genomic riskNode-positive diseaseAdjuvant treatment decisionsLow recurrence scoreShort-term outcomesMultivariate logistic regressionComprehensive cancer centerDX recurrence scoreOncotype DX testingChemotherapy omissionPT1-2N0Upfront surgery
2019
Prognostic Impact of the 21-Gene Recurrence Score Assay Among Young Women With Node-Negative and Node-Positive ER-Positive/HER2-Negative Breast Cancer
Poorvu PD, Gelber SI, Rosenberg SM, Ruddy KJ, Tamimi RM, Collins LC, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Jakubowski DM, Russell C, Winer EP, Partridge AH. Prognostic Impact of the 21-Gene Recurrence Score Assay Among Young Women With Node-Negative and Node-Positive ER-Positive/HER2-Negative Breast Cancer. Journal Of Clinical Oncology 2019, 38: 725-733. PMID: 31809240, PMCID: PMC7048163, DOI: 10.1200/jco.19.01959.Peer-Reviewed Original ResearchConceptsNode-positive breast cancerDistant recurrence-free survivalRecurrence scoreBreast cancerBreast Cancer StudyN0 diseaseN1 diseaseYoung womenYoung Women's Breast Cancer StudyPositive/HER2-negative breast cancerHER2-negative breast cancerHuman epidermal growth factor receptorEarly distant recurrenceEarly-stage estrogenN0 breast cancerRS risk groupsNode-positive diseaseMinority of patientsRecurrence-free survivalYears of ageEpidermal growth factor receptorGrowth factor receptorDistant recurrenceAxillary nodesEligible women
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
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 levelsImmune 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 inhibitionMetastasisInhibitionRemissionXenograftsMiceFrequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE. Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer. Journal Of Clinical Oncology 2016, 34: 1460-1468. PMID: 26976419, PMCID: PMC4872307, DOI: 10.1200/jco.2015.65.0747.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overBreast NeoplasmsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, BRCA1Genes, BRCA2Genetic Predisposition to DiseaseGenetic TestingGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansJewsMiddle AgedNeoplasm StagingOvarian NeoplasmsPredictive Value of TestsPrevalenceProspective StudiesRetrospective StudiesRisk FactorsTriple Negative Breast NeoplasmsConceptsCancer predisposition genesTriple-negative breast cancerBreast cancer predisposition genesBreast cancerPredisposition genesGermline mutationsOvarian cancerNext-generation sequencingBRCA1/2 mutationsCancer susceptibility genesSingle cancer centerFamily cancer historyBreast/ovarian cancerOvarian cancer predisposition genesPredictors of mutationsSusceptibility genesSelect patientsSequential patientsAshkenazi Jewish ancestryCancer CenterCancer historyClinical managementFamily historyBreast/ovarian cancer susceptibility geneOvarian cancer susceptibility genes
2015
TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer
Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, Rugo HS, Liu MC, Stearns V, Come SE, Timms KM, Hartman AR, Borger DR, Finkelstein DM, Garber JE, Ryan PD, Winer EP, Goss PE, Ellisen LW. TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2015, 33: 1902-1909. PMID: 25847936, PMCID: PMC4451173, DOI: 10.1200/jco.2014.57.6660.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBRCA1 ProteinBRCA2 ProteinCarboplatinCisplatinClass I Phosphatidylinositol 3-KinasesDrug Administration ScheduleFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenomic InstabilityHeterozygoteHumansLoss of HeterozygosityMiddle AgedMutationNeoplasm StagingPhosphatidylinositol 3-KinasesTreatment OutcomeTriple Negative Breast NeoplasmsConceptsMetastatic triple-negative breast cancerGermline BRCA1/2 mutationsPhase II clinical trialTriple-negative breast cancerBRCA1/2 mutationsResponse rateClinical trialsBreast cancerMulticenter phase II clinical trialEnd pointSingle-arm phase II clinical trialCoprimary end pointsExploratory end pointsObjective response ratePIK3CA mutation statusSingle-agent platinumLong-term respondersPlatinum-based chemotherapyIdentification of patientsBRCA1/2 mutation carriersGenomic instability signatureGene expression subtypesP73 gene expressionPlatinum monotherapyMutation carriers
2011
Breast Medical Oncologists' Use of Standard Prognostic Factors to Predict a 21‐Gene Recurrence Score
Kamal AH, Loprinzi CL, Reynolds C, Dueck AC, Geiger XJ, Ingle JN, Carlson RW, Hobday TJ, Winer EP, Goetz MP. Breast Medical Oncologists' Use of Standard Prognostic Factors to Predict a 21‐Gene Recurrence Score. The Oncologist 2011, 16: 1359-1366. PMID: 21934103, PMCID: PMC3228065, DOI: 10.1634/theoncologist.2011-0048.Peer-Reviewed Original ResearchConceptsRecurrence scorePrognostic criteriaRS riskTreatment recommendationsIntermediate-risk casesHormone receptor statusLymph node negativeProspective clinical trialsStandard prognostic factorsIntermediate recurrence scoreAbility of oncologistsChemotherapy useChemotherapy recommendationsChemotherapy benefitNode negativePrognostic factorsReceptor statusHistologic typeAcademic oncologistsOncologists' useTumor gradeClinical trialsBreast cancerRS categoryOncologist's ability
2010
Triple-negative breast cancer: disease entity or title of convenience?
Carey L, Winer E, Viale G, Cameron D, Gianni L. Triple-negative breast cancer: disease entity or title of convenience? Nature Reviews Clinical Oncology 2010, 7: 683-692. PMID: 20877296, DOI: 10.1038/nrclinonc.2010.154.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBRCA1 ProteinBreast NeoplasmsCarcinoma, Ductal, BreastCase ManagementCombined Modality TherapyDrug Resistance, NeoplasmFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, BRCA1Genes, erbB-2HumansMitotic IndexNeoplasm InvasivenessNeoplasm MetastasisNeoplasm ProteinsNeoplasm Recurrence, LocalPrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneConceptsTriple negative breast cancer tumorsNew systemic therapiesGood initial responseGroup of tumorsPoly (ADP-ribose) polymerase (PARP) inhibitorsBreast cancer tumorsHormonal therapySystemic therapyLuminal subtypeWorse prognosisClinical trialsDisease entityMTOR inhibitorsAngiogenesis inhibitorsPolymerase inhibitorsTherapeutic agentsCancer tumorsInitial responseTherapyTumorsInhibitorsSrc kinaseAgentsChemotherapyPatientsInternational Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured?
Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, Costa A, Winer EP, Cardoso F. International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured? Journal Of The National Cancer Institute 2010, 102: 456-463. PMID: 20220104, PMCID: PMC3298957, DOI: 10.1093/jnci/djq029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBone NeoplasmsBreast NeoplasmsCatheter AblationChemotherapy, AdjuvantClinical Trials as TopicCongresses as TopicConsensus Development Conferences as TopicDose-Response Relationship, DrugEarly Detection of CancerEuropeFemaleGene Expression ProfilingHumansImmunosuppressive AgentsInterdisciplinary CommunicationInternational CooperationLiver NeoplasmsLung NeoplasmsNeoplasm StagingNeoplastic Cells, CirculatingObserver VariationPatient Care TeamPatient SelectionPractice Guidelines as TopicRadiotherapy, AdjuvantSurvival RateConceptsMetastatic breast cancerOligometastatic diseaseBreast cancerMetastatic lesionsPrimary tumorEuropean Breast Cancer ConferenceFirst consensus recommendationsOptimal local treatmentRapid disease controlAvailable therapeutic optionsSubset of patientsLong-term outcomesLarge retrospective seriesDetectable metastatic lesionsAttractive therapeutic strategyChemotherapy optionsSurvival benefitSystemic therapyTreatment guidelinesRegional chemotherapyRetrospective seriesTask ForceLung metastasesTherapeutic optionsPatient population
2009
Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial
Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, Ravdin P, Bugarini R, Baehner FL, Davidson NE, Sledge GW, Winer EP, Hudis C, Ingle JN, Perez EA, Pritchard KI, Shepherd L, Gralow JR, Yoshizawa C, Allred DC, Osborne CK, Hayes DF, America F. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. The Lancet Oncology 2009, 11: 55-65. PMID: 20005174, PMCID: PMC3058239, DOI: 10.1016/s1470-2045(09)70314-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase III as TopicCyclophosphamideDisease-Free SurvivalDoxorubicinFemaleFluorouracilGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic TestingHumansKaplan-Meier EstimateLymphatic MetastasisMiddle AgedPatient SelectionPostmenopausePredictive Value of TestsProportional Hazards ModelsRandomized Controlled Trials as TopicReceptors, EstrogenRecurrenceRetrospective StudiesReverse Transcriptase Polymerase Chain ReactionRisk AssessmentTamoxifenTime FactorsTreatment OutcomeUnited StatesConceptsLow recurrence scorePositive breast cancerAnthracycline-based chemotherapyDisease-free survivalHigh recurrence scoreRecurrence scorePositive nodesBreast cancerPostmenopausal womenRetrospective analysisNode-positive breast cancerTamoxifen-alone groupTamoxifen-treated patientsPhase 3 trialNational Cancer InstituteEffect of recurrenceOverall survivalSpecific survivalSurvival benefitCox regressionHigh riskTreatment groupsCancer InstituteChemotherapyPredictive value