2023
Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer
Tarantino P, Gupta H, Hughes M, Files J, Strauss S, Kirkner G, Feeney A, Li Y, Garrido-Castro A, Barroso-Sousa R, Bychkovsky B, DiLascio S, Sholl L, MacConaill L, Lindeman N, Johnson B, Meyerson M, Jeselsohn R, Qiu X, Li R, Long H, Winer E, Dillon D, Curigliano G, Cherniack A, Tolaney S, Lin N. Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer. Nature Communications 2023, 14: 7496. PMID: 37980405, PMCID: PMC10657399, DOI: 10.1038/s41467-023-43324-w.Peer-Reviewed Original ResearchConceptsHER2-low tumorsBreast cancerHER2-negative metastatic breast cancerMetastatic breast cancerTumor mutational burdenHigh rateComprehensive genomic characterizationHER2 0Mutational burdenBreast tumorsTumorsHER2Genomic alterationsNext-generation sequencingSignificant differencesGenomic findingsCancerGenomic landscapeMolecular underpinningsHemideletionGenomic characterizationHigher numberPatientsCopy counts
2021
Contribution of tumour and immune cells to PD-L1 as a predictive biomarker in metastatic triple-negative breast cancer (mTNBC): analysis from keynote-119
Emancipator K, Winer E, Lipatov O, Im S, Goncalves A, Muñoz-Couselo E, Lee K, Nowecki Z, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Hund S, Kulangara K, Karantza V, Mejia J, Ma J, Jelinic P, Huang L, Cortes J. Contribution of tumour and immune cells to PD-L1 as a predictive biomarker in metastatic triple-negative breast cancer (mTNBC): analysis from keynote-119. Pathology 2021, 53: s47-s48. DOI: 10.1016/j.pathol.2021.06.099.Peer-Reviewed Original ResearchGenomic Characterization of de novo Metastatic Breast Cancer
Garrido-Castro AC, Spurr LF, Hughes ME, Li YY, Cherniack AD, Kumari P, Lloyd MR, Bychkovsky B, Barroso-Sousa R, Di Lascio S, Jain E, Files J, Mohammed-Abreu A, Krevalin M, MacKichan C, Barry WT, Guo H, Xia D, Cerami E, Rollins BJ, MacConaill LE, Lindeman NI, Krop IE, Johnson BE, Wagle N, Winer EP, Dillon DA, Lin NU. Genomic Characterization of de novo Metastatic Breast Cancer. Clinical Cancer Research 2021, 27: 1105-1118. PMID: 33293374, PMCID: PMC7887078, DOI: 10.1158/1078-0432.ccr-20-1720.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPrimary tumorOverall survivalBreast cancerDe novo metastatic breast cancerNovo metastatic breast cancerDifferential therapeutic sensitivityBetter OSPoor OSShorter OSInitial diagnosisHigh TMBMetastatic tumorsDnMBCCurrent treatmentMutational burdenTreatment selectionMetastatic driversStage IMultiple comparison adjustmentTherapeutic sensitivityTumorsPatientsCancerIntrinsic resistance
2020
The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer
Wander SA, Cohen O, Gong X, Johnson GN, Buendia-Buendia JE, Lloyd MR, Kim D, Luo F, Mao P, Helvie K, Kowalski KJ, Nayar U, Waks AG, Parsons SH, Martinez R, Litchfield LM, Ye XS, Yu C, Jansen VM, Stille JR, Smith PS, Oakley GJ, Chu QS, Batist G, Hughes ME, Kremer JD, Garraway LA, Winer EP, Tolaney SM, Lin NU, Buchanan SG, Wagle N. The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer. Cancer Discovery 2020, 10: 1174-1193. PMID: 32404308, PMCID: PMC8815415, DOI: 10.1158/2159-8290.cd-19-1390.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiopsyBreast NeoplasmsCell Cycle ProteinsCell Line, TumorCheckpoint Kinase 1Drug Resistance, NeoplasmExome SequencingFemaleGenomicsHumansProtein Kinase InhibitorsProto-Oncogene Proteins c-aktProto-Oncogene Proteins p21(ras)Receptors, SteroidRetinoblastoma Binding ProteinsUbiquitin-Protein LigasesConceptsCyclin-dependent kinase 4/6 inhibitorsMetastatic breast cancerBreast cancerResistant tumorsHormone receptor-positive metastatic breast cancerHormone receptor-positive breast cancerReceptor-positive breast cancerEstrogen receptor expressionCandidate resistance mechanismsWhole-exome sequencingPrecision-based approachesCDK4/6i resistanceMechanisms of resistanceReceptor expressionTherapeutic strategiesCDK4/6iTherapeutic opportunitiesPatient samplesTumorsIssue featurePatientsCancerAcquired ResistanceCancer cellsAlterations
2018
The tumor-immune microenvironment (TME) in HR+/HER2- metastatic breast cancer (mBC): Relationship to non-metastatic (met) tumors and prior treatment (tx) received.
Waks A, Tolaney S, Schnitt S, Dillon D, Gjini E, Abdelrahman S, Marino-Enriquez A, Helvie K, Marini L, Cohen O, Kim D, Wander S, Stover D, Rodig S, Krop I, Winer E, Lin N, Wagle N. The tumor-immune microenvironment (TME) in HR+/HER2- metastatic breast cancer (mBC): Relationship to non-metastatic (met) tumors and prior treatment (tx) received. Journal Of Clinical Oncology 2018, 36: 1054-1054. DOI: 10.1200/jco.2018.36.15_suppl.1054.Peer-Reviewed Original Research
2017
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
Adalsteinsson VA, Ha G, Freeman SS, Choudhury AD, Stover DG, Parsons HA, Gydush G, Reed SC, Rotem D, Rhoades J, Loginov D, Livitz D, Rosebrock D, Leshchiner I, Kim J, Stewart C, Rosenberg M, Francis JM, Zhang CZ, Cohen O, Oh C, Ding H, Polak P, Lloyd M, Mahmud S, Helvie K, Merrill MS, Santiago RA, O’Connor E, Jeong SH, Leeson R, Barry RM, Kramkowski JF, Zhang Z, Polacek L, Lohr JG, Schleicher M, Lipscomb E, Saltzman A, Oliver NM, Marini L, Waks AG, Harshman LC, Tolaney SM, Van Allen EM, Winer EP, Lin NU, Nakabayashi M, Taplin ME, Johannessen CM, Garraway LA, Golub TR, Boehm JS, Wagle N, Getz G, Love JC, Meyerson M. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nature Communications 2017, 8: 1324. PMID: 29109393, PMCID: PMC5673918, DOI: 10.1038/s41467-017-00965-y.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingCell-free DNATumor biopsiesTumor whole-exome sequencingTumor contentHigh concordanceClonal somatic mutationsMetastatic tumorsBreast cancerMetastatic prostateBlood samplesPatientsTumor mutationsCfDNA profilingBiopsyMutational signaturesSomatic mutationsTumorsNumber alterationsConcordanceComprehensive profilingNeoantigensSequencingProstateCancerLBA13 Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): Results from KEYNOTE-086
Loi S, Adams S, Schmid P, Cortés J, Cescon D, Winer E, Toppmeyer D, Rugo H, De Laurentiis M, Nanda R, Iwata H, Awada A, Tan A, Wang A, Aktan G, Karantza V, Salgado R. LBA13 Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): Results from KEYNOTE-086. Annals Of Oncology 2017, 28: v608. DOI: 10.1093/annonc/mdx440.005.Peer-Reviewed Original ResearchCDK4/6 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 damageScoresThe Metastatic Breast Cancer Project: A national direct-to-patient initiative to accelerate genomics research.
Wagle N, Painter C, Krevalin M, Oh C, Anderka K, Larkin K, Lennon N, Dillon D, Frank E, Winer E, Lander E, Golub T. The Metastatic Breast Cancer Project: A national direct-to-patient initiative to accelerate genomics research. Journal Of Clinical Oncology 2016, 34: lba1519-lba1519. DOI: 10.1200/jco.2016.34.18_suppl.lba1519.Peer-Reviewed Original ResearchMetastatic breast cancerBreast Cancer ProjectMedical recordsMedian timeBreast cancerDe novo metastatic breast cancerMedical providersCancer ProjectNovo metastatic breast cancerMedian ageInitial diagnosisTumor biopsiesMost tumorsSaliva kitsClinical informationNationwide studyExtraordinary responsePatient approachCommunity settingsTumorsPatient initiativeSaliva samplesTherapyGermline DNACancerOvercoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors
Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, Tuck D, Harris LN, Wong KK, Liu XS, Sicinski P, Winer EP, Krop IE, Zhao JJ. Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors. Cancer Cell 2016, 29: 255-269. PMID: 26977878, PMCID: PMC4794996, DOI: 10.1016/j.ccell.2016.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Disease Models, AnimalDrug Resistance, NeoplasmErbB ReceptorsFemaleHumansMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesNeoplasm Recurrence, LocalPhosphorylationProtein Kinase InhibitorsReceptor, ErbB-2TOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsHER2-positive breast cancerCDK4/6 inhibitorsBreast cancerEGFR/HER2Patient-derived xenograft tumorsTransgenic mouse modelInhibition of CDK4/6Tumor recurrenceXenograft tumorsMouse modelPotent suppressionTransgenic modelClinical specimensTherapeutic resistanceDual inhibitionMediate resistanceHER2CancerTSC2 phosphorylationG1 arrestCellular senescenceTherapyRb phosphorylationTumorsCDK4/6
2012
Evaluation of gene expression by RNA-seq after single dose of trastuzumab (T) reveals predictors of pathologic complete response (pCR) in HER2-positive early breast cancer.
Galanina N, Sprecher E, Bossuyt V, Sarkar S, Krop I, Winer E, Tuck D, Bruce C, Harris L. Evaluation of gene expression by RNA-seq after single dose of trastuzumab (T) reveals predictors of pathologic complete response (pCR) in HER2-positive early breast cancer. Journal Of Clinical Oncology 2012, 30: 10558-10558. DOI: 10.1200/jco.2012.30.15_suppl.10558.Peer-Reviewed Original ResearchPathologic complete responseSingle doseClinical trialsHER2-positive early breast cancerEarly breast cancer patientsEarly breast cancerBreast cancer patientsTumor core biopsiesSubsequent clinical trialsWeek time pointMost gene expression changesComplete responseCancer patientsPredictive markerCore biopsyBreast cancerImmune pathwaysTumorsTime pointsB2MGene expression changesBrief exposureHER2DoseTrials
2011
PL1-1: How To Use Endocrine Therapy for Breast Cancer: Beyond the Basics.
Winer E. PL1-1: How To Use Endocrine Therapy for Breast Cancer: Beyond the Basics. Cancer Research 2011, 71: pl1-1-pl1-1. DOI: 10.1158/0008-5472.sabcs11-pl1-1.Peer-Reviewed Original ResearchHormone receptor-positive diseaseReceptor-positive diseaseEndocrine therapyPositive diseaseBreast cancerClinical practiceExtended adjuvant therapyAdjuvant endocrine therapyBreast cancer patientsAdjuvant therapyHormonal therapyMore treatment choicesPremenopausal womenSufficient therapyLate recurrenceCancer patientsAromatase inhibitorsTreatment choiceHigh riskPatientsTherapyDrug resistanceCancer ResHormone receptorsTumors
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 kinaseAgentsChemotherapyPatientsAdjuvant therapy for postmenopausal women with endocrine-sensitive breast cancer
Freedman RA, Winer EP. Adjuvant therapy for postmenopausal women with endocrine-sensitive breast cancer. The Breast 2010, 19: 69-75. PMID: 20034796, DOI: 10.1016/j.breast.2009.11.009.Peer-Reviewed Original ResearchConceptsEndocrine-sensitive breast cancerAdjuvant endocrine therapyBreast cancerEndocrine therapyPostmenopausal womenEndocrine-sensitive tumorsMultiple clinical trialsAdjuvant therapyClinical trialsTreatment benefitCurrent recommendationsTherapyAvailable evidenceTranslational questionsCancerWomenFuture studiesTumorsTrials
2009
Topoisomerase IIα Amplification Does Not Predict Benefit From Dose-Intense Cyclophosphamide, Doxorubicin, and Fluorouracil Therapy in HER2-Amplified Early Breast Cancer: Results of CALGB 8541/150013
Harris LN, Broadwater G, Abu-Khalaf M, Cowan D, Thor AD, Budman D, Cirrincione CT, Berry DA, Winer EP, Hudis CA, Hayes DF, Friedman P, Ellis M, Dressler L. Topoisomerase IIα Amplification Does Not Predict Benefit From Dose-Intense Cyclophosphamide, Doxorubicin, and Fluorouracil Therapy in HER2-Amplified Early Breast Cancer: Results of CALGB 8541/150013. Journal Of Clinical Oncology 2009, 27: 3430-3436. PMID: 19470942, PMCID: PMC4979079, DOI: 10.1200/jco.2008.18.4085.Peer-Reviewed Original ResearchMeSH KeywordsAnthracyclinesAntibiotics, AntineoplasticAntigens, NeoplasmAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCyclophosphamideDNA Topoisomerases, Type IIDNA-Binding ProteinsDoxorubicinDrug InteractionsFluorouracilGene AmplificationHumansImmunohistochemistryReceptor, ErbB-2
2006
Tumor Therapeutic Response and Vessel Tortuosity: Preliminary Report in Metastatic Breast Cancer
Bullitt E, Lin NU, Ewend MG, Zeng D, Winer EP, Carey LA, Smith JK. Tumor Therapeutic Response and Vessel Tortuosity: Preliminary Report in Metastatic Breast Cancer. Lecture Notes In Computer Science 2006, 9: 561-568. PMID: 17354817, PMCID: PMC2504703, DOI: 10.1007/11866763_69.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerMetastatic brain tumorsTumor therapeutic responseBrain tumor therapyCurrent non-invasive methodsNon-invasive methodTumor responseTherapeutic responseTumor activityBrain tumorsVessel tortuosityPreliminary reportTumor therapyCancerTreatmentMRAPreliminary studyReportPatientsStatistical analysisTherapyTumorsMonthsResponse
2005
Optimizing endocrine therapy in postmenopausal women with early stage breast cancer: A decision analysis for biological subsets of tumors
Burstein H, Winer E, Kuntz K, Weeks J, Punglia R. Optimizing endocrine therapy in postmenopausal women with early stage breast cancer: A decision analysis for biological subsets of tumors. Journal Of Clinical Oncology 2005, 23: 529-529. DOI: 10.1200/jco.2005.23.16_suppl.529.Peer-Reviewed Original Research