2019
PIK3CA and MAP3K1 alterations imply luminal A status and are associated with clinical benefit from pan-PI3K inhibitor buparlisib and letrozole in ER+ metastatic breast cancer
Nixon MJ, Formisano L, Mayer IA, Estrada MV, González-Ericsson PI, Isakoff SJ, Forero-Torres A, Won H, Sanders ME, Solit DB, Berger MF, Cantley LC, Winer EP, Arteaga CL, Balko JM. PIK3CA and MAP3K1 alterations imply luminal A status and are associated with clinical benefit from pan-PI3K inhibitor buparlisib and letrozole in ER+ metastatic breast cancer. Npj Breast Cancer 2019, 5: 31. PMID: 31552290, PMCID: PMC6757060, DOI: 10.1038/s41523-019-0126-6.Peer-Reviewed Original ResearchMetastatic breast cancerClinical benefitBreast cancerPan-PI3K inhibitor buparlisibHuman epidermal growth factor 2Epidermal growth factor 2K inhibitorsPan-PI3K inhibitorPhase Ib studySubset of patientsPI3KBreast cancer cell linesPI3K inhibitorsPAM50 analysisCancer cell linesEndocrine therapyGrowth factor 2Only biomarkerPIK3CA mutationsClinical trialsMetastatic tissuesTherapeutic combinationsIb studyPatientsBuparlisib
2016
Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer
Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, Janiszewska M, Jin Huh S, Liang Y, Ryan J, Doherty E, Mohammed H, Guo H, Stover DG, Ekram MB, Peluffo G, Brown J, D’Santos C, Krop I, Dillon D, McKeown M, Ott C, Qi J, Ni M, Rao P, Duarte M, Wu S, Chiang C, Anders L, Young R, Winer E, Letai A, Barry W, Carroll J, Long H, Brown M, Shirley Liu X, Meyer C, Bradner J, Polyak K. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature 2016, 529: 413-417. PMID: 26735014, PMCID: PMC4854653, DOI: 10.1038/nature16508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzepinesBinding, CompetitiveCasein Kinase IICell Cycle ProteinsCell Line, TumorCell ProliferationChromatinDrug Resistance, NeoplasmEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticGenome, HumanHumansMediator Complex Subunit 1MiceNuclear ProteinsPhosphorylationPhosphoserineProtein BindingProtein Phosphatase 2Protein Structure, TertiaryProteomicsTranscription FactorsTranscription, GeneticTriazolesTriple Negative Breast NeoplasmsXenograft Model Antitumor Assays
2014
Stand Up to Cancer Phase Ib Study of Pan-Phosphoinositide-3-Kinase Inhibitor Buparlisib With Letrozole in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer
Mayer IA, Abramson VG, Isakoff SJ, Forero A, Balko JM, Kuba MG, Sanders ME, Yap JT, Van den Abbeele AD, Li Y, Cantley LC, Winer E, Arteaga CL. Stand Up to Cancer Phase Ib Study of Pan-Phosphoinositide-3-Kinase Inhibitor Buparlisib With Letrozole in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. Journal Of Clinical Oncology 2014, 32: 1202-1209. PMID: 24663045, PMCID: PMC3986383, DOI: 10.1200/jco.2013.54.0518.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCell Line, TumorClass I Phosphatidylinositol 3-KinasesDose-Response Relationship, DrugDrug Administration ScheduleFemaleFluorodeoxyglucose F18HumansLetrozoleMiddle AgedMorpholinesMultimodal ImagingNitrilesPhosphoinositide-3 Kinase InhibitorsPositron-Emission TomographyProtein Kinase InhibitorsRadiopharmaceuticalsReceptor, ErbB-2Receptors, EstrogenTomography, X-Ray ComputedTriazolesConceptsMaximum-tolerated dosePhase Ib studyPET/CTEndocrine therapyDisease progressionBreast cancerIb studyCommon drug-related adverse eventsDrug-related adverse eventsPIK3CA hot spot mutationsPositive breast cancer cell linesER-positive breast cancerPositron emission tomography/Human epidermal growth factor receptorBreast cancer refractoryClinical benefit rateOral reversible inhibitorPIK3CA mutation statusPhase III trialsMetastatic breast cancerRapid disease progressionEmission tomography/Different administration schedulesBreast cancer cell linesMetabolic disease progression
2011
PD09-04: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of the PI3-Kinase Inhibitor GDC-0941 in Combination with Paclitaxel and Bevacizumab in Patients with Locally Recurrent or Metastatic Breast Cancer.
Schöffski P, De Benedictis E, Gendreau S, Gianni L, Krop I, Levy G, Ware J, Wildiers H, Winer E. PD09-04: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of the PI3-Kinase Inhibitor GDC-0941 in Combination with Paclitaxel and Bevacizumab in Patients with Locally Recurrent or Metastatic Breast Cancer. Cancer Research 2011, 71: pd09-04-pd09-04. DOI: 10.1158/0008-5472.sabcs11-pd09-04.Peer-Reviewed Original ResearchMetastatic BCDay 1Prior treatmentPhase Ib studyDose-escalation studySubclavian vein thrombosisMetastatic breast cancerSingle-agent activityDose-escalation designCycle 1Breast cancer cell linesClass I PI3K isoformsAnti-cancer therapyPI3K pathwayPhosphorylation of AktAdditional DLTsCancer cell linesDrug holidayOpen labelVein thrombosisEscalation designPI3K isoformsLocally RecurrentChemotherapy treatmentCohort 2P1-06-23: Changes in Gene Expression after One Dose of Trastuzumab (T) in HER2+ Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2 Positive Early Stage Breast Cancer.
Sprecher E, Lezon-Geyda K, Sarkar S, Bossuyt V, Narayaan M, Kumar A, Krop I, Winer E, Tuck D, Kleinstein S, Harris L. P1-06-23: Changes in Gene Expression after One Dose of Trastuzumab (T) in HER2+ Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2 Positive Early Stage Breast Cancer. Cancer Research 2011, 71: p1-06-23-p1-06-23. DOI: 10.1158/0008-5472.sabcs11-p1-06-23.Peer-Reviewed Original ResearchPathologic complete responseBreast cancer patientsBreast cancer cell linesSensitive cell linesCancer cell linesCancer patientsSingle doseBreast cancerHER2-positive early-stage breast cancerPositive early-stage breast cancerCell linesBreast tumorsEarly breast cancer patientsEarly-stage breast cancerDose of trastuzumabEarly-stage HER2Early breast cancerResistant breast tumorsStage breast cancerTumor core biopsiesPathway analysisMechanism of actionResistant HER2RECIST criteriaClinical responseAssociation between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumors
Sprecher E, Sarkar S, Kleinstein S, Narayan M, Winer E, Tuck D, Lezon-Geyda K, Krop I, Harris L. Association between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumors. 2011, 446-450. DOI: 10.1145/2147805.2147867.Peer-Reviewed Original ResearchEarly-stage HER2Breast cancer patientsBreast tumorsTrastuzumab treatmentCancer patientsCell linesHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Breast cancer settingGrowth factor receptor 2Resistant breast tumorsTrastuzumab-resistant HER2Breast cancer cell linesClinical treatment decisionsFactor receptor 2Trastuzumab exposureCancer cell linesGene expression signaturesResponsive patientsTrastuzumab resistanceSingle doseTargeted therapyBreast cancerCancer settingTreatment decisions
2006
Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806
Rincon M, Broadwater G, Harris L, Crocker A, Weaver D, Dressler L, Berry D, Sutton L, Michaelson R, Messino M, Kirshner J, Fleming G, Winer E, Hudis C, Appel S, Norton L, Muss H, for the Cancer and Leukemia Group B. Interleukin-6, multidrug resistance protein-1 expression and response to paclitaxel in women with metastatic breast cancer: results of cancer and leukemia group B trial 159806. Breast Cancer Research And Treatment 2006, 100: 301-308. PMID: 16773437, DOI: 10.1007/s10549-006-9251-7.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerInterleukin-6Breast cancerP-glycoproteinPgp expressionMultidrug resistance protein-1 expressionSingle-agent paclitaxelElevated serum levelsBreast cancer patientsBreast cancer cell linesProtein-1 expressionResult of cancerMulti-drug resistanceCancer cell linesClinical characteristicsOverall survivalPartial responseSerum levelsTreatment armsWorse prognosisPredictive factorsCancer patientsPredictive markerIHC expressionPaclitaxel sensitivity