2022
Treatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03).
Mayer EL, Fesl C, Hlauschek D, Garcia-Estevez L, Burstein HJ, Zdenkowski N, Wette V, Miller KD, Balic M, Mayer IA, Cameron D, Winer EP, Ponce Lorenzo JJ, Lake D, Pristauz-Telsnigg G, Haddad TC, Shepherd L, Iwata H, Goetz M, Cardoso F, Traina TA, Sabanathan D, Breitenstein U, Ackerl K, Metzger Filho O, Zehetner K, Solomon K, El-Abed S, Theall KP, Lu DR, Dueck A, Gnant M, DeMichele A. Treatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03). Journal Of Clinical Oncology 2022, 40: 449-458. PMID: 34995105, PMCID: PMC9851679, DOI: 10.1200/jco.21.01918.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleHumansNeoplasm StagingPiperazinesProtein Kinase InhibitorsPyridinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRisk FactorsTime FactorsConceptsInvasive disease-free survivalAdjuvant endocrine therapyHuman epidermal growth factor receptorEndocrine therapyEpidermal growth factor receptorPalbociclib exposureGrowth factor receptorBreast cancerHormone Receptor-Positive/Human Epidermal Growth Factor ReceptorAddition of palbociclibNovel adjuvant treatmentDisease-free survivalEarly breast cancerFactor receptorOral cancer therapyProtocol analysisPALLAS studyAdjuvant treatmentEarly discontinuationAdjuvant studiesDiscontinuation ratesDose modificationAnalysis populationCDK4/6 inhibitorsDrug persistence
2020
CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity
Watt AC, Cejas P, DeCristo MJ, Metzger-Filho O, Lam EYN, Qiu X, BrinJones H, Kesten N, Coulson R, Font-Tello A, Lim K, Vadhi R, Daniels VW, Montero J, Taing L, Meyer CA, Gilan O, Bell CC, Korthauer KD, Giambartolomei C, Pasaniuc B, Seo JH, Freedman ML, Ma C, Ellis MJ, Krop I, Winer E, Letai A, Brown M, Dawson MA, Long HW, Zhao JJ, Goel S. CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity. Nature Cancer 2020, 2: 34-48. PMID: 33997789, PMCID: PMC8115221, DOI: 10.1038/s43018-020-00135-y.Peer-Reviewed Original ResearchConceptsSet of enhancersTranscription factor proteinsAP-1 transcriptional activityEndogenous retroviral elementsCell cycle arrestEnhancer landscapeCyclin-dependent kinase 4Cancer cell cycle arrestEnhancer activationCell chromatinApoptotic evasionTranscriptional activityPathway biologyRetroviral elementsApoptotic responsePharmacologic inhibitorsCancer cell immunogenicityFactor proteinNew enhancersKinase 4Cycle arrestLuminal differentiationCDK4/6 inhibitionCDK4/6 inhibitorsEnhancer
2018
Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer
Kuang Y, Siddiqui B, Hu J, Pun M, Cornwell M, Buchwalter G, Hughes ME, Wagle N, Kirschmeier P, Jänne PA, Paweletz CP, Lin NU, Krop IE, Barry WT, Winer EP, Brown M, Jeselsohn R. Unraveling the clinicopathological features driving the emergence of ESR1 mutations in metastatic breast cancer. Npj Breast Cancer 2018, 4: 22. PMID: 30083595, PMCID: PMC6072793, DOI: 10.1038/s41523-018-0075-5.Peer-Reviewed Original ResearchMetastatic breast cancerESR1 mutationsBreast cancerMetastatic settingClinicopathological featuresPIK3CA mutationsAromatase inhibitorsER-positive metastatic breast cancerDetailed clinical dataSpecific systemic treatmentMetastatic treatmentDistant recurrenceMetastatic diseaseSystemic treatmentPrimary diseaseEndocrine resistanceCDK4/6 inhibitorsPathological featuresFulvestrant treatmentClinical dataPrior treatmentSignificant associationPatientsCancerPrevalenceA phase I study of palbociclib (PALBO) plus everolimus (EVE) and exemestane (EXE) in hormone-receptor positive (HR+)/HER2- metastatic breast cancer (MBC) after progression on a CDK4/6 inhibitor (CDK4/6i): safety, tolerability and pharmacokinetic (PK) analysis.
Barroso-Sousa R, Guo H, Barry W, Ferreira A, Rees R, Winer E, Wagle N, Tolaney S. A phase I study of palbociclib (PALBO) plus everolimus (EVE) and exemestane (EXE) in hormone-receptor positive (HR+)/HER2- metastatic breast cancer (MBC) after progression on a CDK4/6 inhibitor (CDK4/6i): safety, tolerability and pharmacokinetic (PK) analysis. Journal Of Clinical Oncology 2018, 36: 1068-1068. DOI: 10.1200/jco.2018.36.15_suppl.1068.Peer-Reviewed Original ResearchCDK4/6 inhibition in breast cancer: current practice and future directions
Pernas S, Tolaney SM, Winer EP, Goel S. CDK4/6 inhibition in breast cancer: current practice and future directions. Therapeutic Advances In Medical Oncology 2018, 10: 1758835918786451. PMID: 30038670, PMCID: PMC6050811, DOI: 10.1177/1758835918786451.Peer-Reviewed Original ResearchCDK4/6 inhibitorsBreast cancerNovel immune-based therapiesPositive breast cancer patientsER-positive breast cancerProgression-free survivalImmune-based therapiesBreast cancer patientsCancer cell cycle arrestClinical trial resultsSelective CDK4/6 inhibitorsNormal breast epitheliumCyclin-dependent kinase 4Breast cancer cellsCyclin D/cyclin-dependent kinase 4Cancer cell cycleEndocrine therapyCDK4/6 pathwayCDK4/6 inhibitionCancer patientsCell cycle arrestClinical dataEstrogen receptorPreclinical studiesBreast epithelium
2016
Overcoming 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