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
2020
Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer
Axelrod ML, Nixon MJ, Gonzalez-Ericsson PI, Bergman RE, Pilkinton MA, McDonnell WJ, Sanchez V, Opalenik SR, Loi S, Zhou J, Mackay S, Rexer BN, Abramson VG, Jansen VM, Mallal S, Donaldson J, Tolaney SM, Krop IE, Garrido-Castro AC, Marotti JD, Shee K, Miller TW, Sanders ME, Mayer IA, Salgado R, Balko JM. Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer. Clinical Cancer Research 2020, 26: 5668-5681. PMID: 32826327, PMCID: PMC7642197, DOI: 10.1158/1078-0432.ccr-19-3685.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlbuminsAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCD8-Positive T-LymphocytesFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyNeoplasm ProteinsNeoplasm Recurrence, LocalPaclitaxelPrognosisProgrammed Cell Death 1 ReceptorProgression-Free SurvivalTreatment OutcomeTriple Negative Breast NeoplasmsTumor MicroenvironmentConceptsTriple-negative breast cancerTumor immune microenvironmentNeoadjuvant chemotherapyOverall survivalBreast cancerPeripheral bloodResidual diseaseMetastatic triple-negative breast cancerEffect of NACImproved long-term outcomesActive antitumor immunityLocal tumor immunityRole of chemotherapyT-cell signatureLong-term outcomesPeripheral T cellsMultiple immune-related genesImmune-related genesNab-paclitaxelImmunologic effectsMicrometastatic diseasePersistent diseaseAntitumor immunityTumor immunityClinical outcomesEffect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer
Tolaney SM, Barroso-Sousa R, Keenan T, Li T, Trippa L, Vaz-Luis I, Wulf G, Spring L, Sinclair NF, Andrews C, Pittenger J, Richardson ET, Dillon D, Lin NU, Overmoyer B, Partridge AH, Van Allen E, Mittendorf EA, Winer EP, Krop IE. Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer. JAMA Oncology 2020, 6: 1598-1605. PMID: 32880602, PMCID: PMC7489368, DOI: 10.1001/jamaoncol.2020.3524.Peer-Reviewed Original ResearchConceptsProgression-free survivalObjective response rateTumor-infiltrating lymphocytesTumor mutational burdenPD-L1 statusOverall survivalHormonal therapyPrior linesPD-L1Clinical trialsMedian numberDay 1Cell death ligand 1 (PD-L1) inhibitorsERBB2-negative metastatic breast cancerMedian progression-free survivalDeath ligand 1 (PD-L1) inhibitorsEnd pointCause adverse eventsEfficacy of eribulinHormone receptor positiveMulticenter phase 2PD-L1 22C3Treatment-related deathsLines of chemotherapyPrimary end pointTumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer
Barroso-Sousa R, Keenan TE, Pernas S, Exman P, Jain E, Garrido-Castro AC, Hughes M, Bychkovsky B, Umeton R, Files JL, Lindeman NI, MacConaill LE, Hodi FS, Krop IE, Dillon D, Winer EP, Wagle N, Lin NU, Mittendorf EA, Van Allen EM, Tolaney SM. Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2020, 26: 2565-2572. PMID: 32019858, PMCID: PMC7269810, DOI: 10.1158/1078-0432.ccr-19-3507.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerHigh tumor mutational burdenProgression-free survivalTumor mutational burdenObjective response rateImmune checkpoint inhibitorsAnti-PD-1/L1 therapyTriple-negative breast cancerOverall survivalL1 therapyPD-L1Breast cancerMutational burdenLow objective response rateLonger progression-free survivalShorter progression-free survivalDana-Farber Cancer InstituteTumor genomic featuresShorter overall survivalMutations/megabaseCheckpoint inhibitorsVisceral metastasesL1 blockadePerformance statusPrior lines
2019
The Immune Microenvironment in Hormone Receptor–Positive Breast Cancer Before and After Preoperative Chemotherapy
Waks AG, Stover DG, Guerriero JL, Dillon D, Barry WT, Gjini E, Hartl C, Lo W, Savoie J, Brock J, Wesolowski R, Li Z, Damicis A, Philips AV, Wu Y, Yang F, Sullivan A, Danaher P, Brauer HA, Osmani W, Lipschitz M, Hoadley KA, Goldberg M, Perou CM, Rodig S, Winer EP, Krop IE, Mittendorf EA, Tolaney SM. The Immune Microenvironment in Hormone Receptor–Positive Breast Cancer Before and After Preoperative Chemotherapy. Clinical Cancer Research 2019, 25: 4644-4655. PMID: 31061067, PMCID: PMC6677598, DOI: 10.1158/1078-0432.ccr-19-0173.Peer-Reviewed Original ResearchConceptsStromal tumor-infiltrating lymphocytesImmune microenvironmentNeoadjuvant chemotherapyPD-L1Breast cancerHormone receptor-positive breast cancerBreast tumorsHormone receptor-positive/HER2-negative breast cancerHER2-negative breast cancerDistant metastasis-free survivalReceptor-positive breast cancerImmunotherapy-based approachesPAM50 intrinsic subtypesCheckpoint inhibitor therapyPD-L1 stainingTumor-infiltrating lymphocytesMetastasis-free survivalMacrophage-targeted therapiesRole of macrophagesPreoperative chemotherapyStandard chemotherapyInhibitor therapyResidual diseaseMyeloid signaturePoor responseThe immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial
Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, Osmani W, Getz A, Baltay M, Dang C, Yardley D, Moy B, Marcom PK, Mittendorf EA, Krop IE, Winer EP, Tolaney SM. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Annals Of Oncology 2019, 30: 575-581. PMID: 30753274, PMCID: PMC8033534, DOI: 10.1093/annonc/mdz047.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorBreastBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMastectomyMiddle AgedPaclitaxelReceptor, ErbB-2TrastuzumabTumor BurdenTumor MicroenvironmentConceptsHER2-positive breast cancerSmall HER2-positive breast cancersImmune gene signaturesBreast cancerImmune profileAPT trialPD-L1Immune markersImmune microenvironmentSmall HER2-positive tumorsStromal PD-L1 expressionNode-negative breast cancerCell signatureGene signatureHuman epidermal growth factor receptorStromal PD-L1PD-L1 expressionHistological grade 2Luminal B tumorsB cell signaturesBreast cancer trialsHER2-positive tumorsImmune cell signaturesBasal-like tumorsHistological grade 1