2022
Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit.
Barroso-Sousa R, Forman J, Collier K, Weber ZT, Jammihal TR, Kao KZ, Richardson ET, Keenan T, Cohen O, Manos MP, Brennick RC, Ott PA, Hodi FS, Dillon DA, Attaya V, O'Meara T, Lin NU, Van Allen EM, Rodig S, Winer EP, Mittendorf EA, Wu CJ, Wagle N, Stover DG, Shukla SA, Tolaney SM. Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit. JCO Precision Oncology 2022, 6: e2100413. PMID: 35797509, PMCID: PMC9848556, DOI: 10.1200/po.21.00413.Peer-Reviewed Original ResearchConceptsGene expression pathwaysMetastatic triple-negative breast cancerExpression pathwaysWhole-exome sequencingFollicular helper T cellsDNA damage repair pathwaysTriple-negative breast cancerProgression-free survivalMemory T cellsDamage repair pathwaysHelper T cellsTumor mutational burdenT cellsClonal evolutionOverall survivalDNA whole-exome sequencingTranscriptomic landscapeHomologous recombinationRepair pathwaysRNA sequencingM1 macrophagesBreast cancerDefective repairMutational burdenDNA damageSTING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer
Wang Q, Bergholz JS, Ding L, Lin Z, Kabraji SK, Hughes ME, He X, Xie S, Jiang T, Wang W, Zoeller JJ, Kim HJ, Roberts TM, Konstantinopoulos PA, Matulonis UA, Dillon DA, Winer EP, Lin NU, Zhao JJ. STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer. Nature Communications 2022, 13: 3022. PMID: 35641483, PMCID: PMC9156717, DOI: 10.1038/s41467-022-30568-1.Peer-Reviewed Original ResearchConceptsAnti-tumor immunityBreast cancerPARP inhibitorsSTING agonistsBRCA-mutant breast cancerTumor cellsAnti-tumor stateAdvanced ovarian tumorsCell-mediated suppressionType I IFN responseTumor-associated macrophagesInnate immune suppressionI IFN responseBreast tumor cellsTreatment landscapePro-tumor macrophagesImmune suppressionOvarian tumorsImmune cellsBRCA mutationsSystemic administrationT cellsMouse modelTherapeutic benefitBreast tumors
2021
Genomic 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