2020
Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavilá J, Serra V, Prat A, Paré L, Céliz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Research 2020, 22: 120. PMID: 33138866, PMCID: PMC7607628, DOI: 10.1186/s13058-020-01354-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClass I Phosphatidylinositol 3-KinasesDisease ProgressionFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedMorpholinesNeoplasm MetastasisPatient SafetyProtein Kinase InhibitorsProteomicsResponse Evaluation Criteria in Solid TumorsSurvival RateTreatment OutcomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerProgression-free survivalPan-class I PI3K inhibitorMetastatic triple-negative breast cancerStable diseasePhase 2 studyBreast cancerOverall survivalPI3K inhibitorsPI3K pathwayPartial responseComplete responseClinical benefitSingle-arm phase 2 studyTriple-negative metastatic breast cancerMedian progression-free survivalK inhibitorsClinical benefit rateEfficacy of buparlisibK pathwayFrequent adverse eventsMedian overall survivalPercent of patientsMetastatic breast cancerSubset of patients
2019
Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation
Xing Y, Lin NU, Maurer MA, Chen H, Mahvash A, Sahin A, Akcakanat A, Li Y, Abramson V, Litton J, Chavez-MacGregor M, Valero V, Piha-Paul SA, Hong D, Do KA, Tarco E, Riall D, Eterovic AK, Wulf GM, Cantley LC, Mills GB, Doyle LA, Winer E, Hortobagyi GN, Gonzalez-Angulo AM, Meric-Bernstam F. Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation. Breast Cancer Research 2019, 21: 78. PMID: 31277699, PMCID: PMC6612080, DOI: 10.1186/s13058-019-1154-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBiomarkersBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDrug MonitoringFemaleHeterocyclic Compounds, 3-RingHigh-Throughput Nucleotide SequencingHumansImmunohistochemistryMiddle AgedMutationNeoplasm MetastasisNeoplasm StagingProtein Kinase InhibitorsProto-Oncogene Proteins c-aktTreatment OutcomeConceptsObjective response ratePeripheral blood mononuclear cellsPlatelet-rich plasmaAdvanced breast cancerPhase II trialPre-treatment biopsiesBreast cancerAKT inhibitor MKAKT1 mutationsPTEN lossII trialPIK3CA mutationsPIK3CA/AKT1 mutationsAdvanced breast cancer patientsInhibitor MKTriple-negative breast cancerMethodsThe primary endpointPIK3CA/AKT1Common adverse eventsPre-treated patientsProgression-free survivalResultsTwenty-seven patientsBreast cancer patientsBlood mononuclear cellsPTEN mutationsA Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB)
Mayer IA, Prat A, Egle D, Blau S, Fidalgo JAP, Gnant M, Fasching PA, Colleoni M, Wolff AC, Winer EP, Singer CF, Hurvitz S, Estévez LG, van Dam PA, Kümmel S, Mundhenke C, Holmes F, Babbar N, Charbonnier L, Diaz-Padilla I, Vogl FD, Sellami D, Arteaga CL. A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB). Clinical Cancer Research 2019, 25: 2975-2987. PMID: 30723140, PMCID: PMC6522303, DOI: 10.1158/1078-0432.ccr-18-3160.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCell ProliferationClass I Phosphatidylinositol 3-KinasesFemaleHigh-Throughput Nucleotide SequencingHumansLetrozoleMiddle AgedMutationNeoadjuvant TherapyReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionThiazolesTreatment OutcomeConceptsObjective response rateMetastatic breast cancerBreast cancerResponse rateLetrozole treatmentPathologic complete response ratePhase II Randomized StudyHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorComplete response rateHormone receptor positiveMaculo-papular rashProgression-free survivalGrowth factor receptor 2Early breast cancerPhase I studiesWild-type cohortsFactor receptor 2Epidermal growth factor receptorCombination of alpelisibGrowth factor receptorNeoadjuvant letrozoleNeoadjuvant settingPrimary endpoint
2016
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE. Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer. Journal Of Clinical Oncology 2016, 34: 1460-1468. PMID: 26976419, PMCID: PMC4872307, DOI: 10.1200/jco.2015.65.0747.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overBreast NeoplasmsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, BRCA1Genes, BRCA2Genetic Predisposition to DiseaseGenetic TestingGerm-Line MutationHigh-Throughput Nucleotide SequencingHumansJewsMiddle AgedNeoplasm StagingOvarian NeoplasmsPredictive Value of TestsPrevalenceProspective StudiesRetrospective StudiesRisk FactorsTriple Negative Breast NeoplasmsConceptsCancer predisposition genesTriple-negative breast cancerBreast cancer predisposition genesBreast cancerPredisposition genesGermline mutationsOvarian cancerNext-generation sequencingBRCA1/2 mutationsCancer susceptibility genesSingle cancer centerFamily cancer historyBreast/ovarian cancerOvarian cancer predisposition genesPredictors of mutationsSusceptibility genesSelect patientsSequential patientsAshkenazi Jewish ancestryCancer CenterCancer historyClinical managementFamily historyBreast/ovarian cancer susceptibility geneOvarian cancer susceptibility genes
2015
Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets
Brastianos PK, Carter SL, Santagata S, Cahill DP, Taylor-Weiner A, Jones RT, Van Allen EM, Lawrence MS, Horowitz PM, Cibulskis K, Ligon KL, Tabernero J, Seoane J, Martinez-Saez E, Curry WT, Dunn IF, Paek SH, Park SH, McKenna A, Chevalier A, Rosenberg M, Barker FG, Gill CM, Van Hummelen P, Thorner AR, Johnson BE, Hoang MP, Choueiri TK, Signoretti S, Sougnez C, Rabin MS, Lin NU, Winer EP, Stemmer-Rachamimov A, Meyerson M, Garraway L, Gabriel S, Lander ES, Beroukhim R, Batchelor TT, Baselga J, Louis DN, Getz G, Hahn WC. Genomic Characterization of Brain Metastases Reveals Branched Evolution and Potential Therapeutic Targets. Cancer Discovery 2015, 5: 1164-1177. PMID: 26410082, PMCID: PMC4916970, DOI: 10.1158/2159-8290.cd-15-0369.Peer-Reviewed Original ResearchConceptsBrain metastasesPrimary tumorPrimary biopsiesRegional lymph node metastasisLymph node metastasisPI3K/Akt/mTORRegional lymph nodesPotential therapeutic targetPrimary tumor biopsiesPrimary tumor samplesAkt/mTORDistinct genetic alterationsWhole-exome sequencingExtracranial metastasesLymph nodesNode metastasisDismal prognosisActionable alterationsMetastasis sitesInformative alterationsIndividualized therapyTherapeutic targetMetastasisPrimary siteEGFR inhibitors