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
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 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 cellsAlterationsPrevalence and mutational determinants of high tumor mutation burden in breast cancer
Barroso-Sousa R, Jain E, Cohen O, Kim D, Buendia-Buendia J, Winer E, Lin N, Tolaney S, Wagle N. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Annals Of Oncology 2020, 31: 387-394. PMID: 32067680, DOI: 10.1016/j.annonc.2019.11.010.Peer-Reviewed Original ResearchConceptsHigh tumor mutation burdenTumor mutation burdenPD-1 inhibitorsBreast cancerMutation burdenMedian tumor mutation burdenDifferent mutational signaturesPembrolizumab-based therapyMetastatic breast cancerSubset of patientsMut/MbMismatch repair deficiencyGenomic profilesMutational patternsAPOBEC activityGene panel sequencingMultiple tumor typesWhole-exome sequencingDe-identified dataDurable responsesMetastatic tumorsPrimary tumorTumor subtypesPatientsTumor types
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
2017
Genomic Profiling in Node-Positive ER-Positive Early Breast Cancer: Can Tumor Biology Guide Locoregional Therapy?
Garrido-Castro AC, Winer EP. Genomic Profiling in Node-Positive ER-Positive Early Breast Cancer: Can Tumor Biology Guide Locoregional Therapy? Journal Of The National Cancer Institute 2017, 109: djw316. PMID: 28376163, DOI: 10.1093/jnci/djw316.Peer-Reviewed Original Research
2015
Genomic Analysis Reveals That Immune Function Genes Are Strongly Linked to Clinical Outcome in the North Central Cancer Treatment Group N9831 Adjuvant Trastuzumab Trial
Perez EA, Thompson EA, Ballman KV, Anderson SK, Asmann YW, Kalari KR, Eckel-Passow JE, Dueck AC, Tenner KS, Jen J, Fan JB, Geiger XJ, McCullough AE, Chen B, Jenkins RB, Sledge GW, Winer EP, Gralow JR, Reinholz MM. Genomic Analysis Reveals That Immune Function Genes Are Strongly Linked to Clinical Outcome in the North Central Cancer Treatment Group N9831 Adjuvant Trastuzumab Trial. Journal Of Clinical Oncology 2015, 33: 701-708. PMID: 25605861, PMCID: PMC4334774, DOI: 10.1200/jco.2014.57.6298.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDNA, NeoplasmFemaleGene Expression Regulation, NeoplasticGenomicsHumansKaplan-Meier EstimateMiddle AgedMolecular Targeted TherapyProportional Hazards ModelsReceptor, ErbB-2TranscriptomeTrastuzumabConceptsRelapse-free survivalImmune function genesAdjuvant trastuzumab trialsArm BTrastuzumab trialsHazard ratioArm AHuman epidermal growth factor receptorClinicopathologic risk factorsProportional hazard ratiosEpidermal growth factor receptorGrowth factor receptorAdjuvant trastuzumabC patientsCombination chemotherapyClinical outcomesRisk factorsBreast cancerPatientsTrastuzumabPredictive signatureFunction genesChemotherapyGene enrichmentFactor receptor