2014
Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer
Fuentes-Mattei E, Velazquez-Torres G, Phan L, Zhang F, Chou PC, Shin JH, Choi HH, Chen JS, Zhao R, Chen J, Gully C, Carlock C, Qi Y, Zhang Y, Wu Y, Esteva FJ, Luo Y, McKeehan WL, Ensor J, Hortobagyi GN, Pusztai L, Symmans W, Lee MH, Yeung SC. Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer. Journal Of The National Cancer Institute 2014, 106: dju158. PMID: 24957076, PMCID: PMC4110474, DOI: 10.1093/jnci/dju158.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipokinesAgedAnimalsAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsCell ProliferationDisease Models, AnimalEverolimusFemaleHumansKaplan-Meier EstimateMetforminMiceMice, TransgenicMiddle AgedObesityPostmenopauseProspective StudiesProto-Oncogene Proteins c-aktReceptors, EstrogenSignal TransductionSirolimusTOR Serine-Threonine KinasesTranscriptomeConceptsEstrogen receptor-positive breast cancerReceptor-positive breast cancerBreast cancer cell proliferationEffect of obesityBreast cancer patientsObese mouse modelAdipocyte-secreted adipokineCancer cell proliferationCancer patientsBreast cancerMouse modelCell proliferationAssociation of obesityAkt/mTOR activationMammary tumor growthEpithelial-mesenchymal transition genesAKT/mTOR pathwayBreast cancer aggressivenessBreast tumor formationCancer hallmarksPostmenopausal womenPretreatment biopsiesProspective cohortAdipokine secretionCancer deathOpen-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †
Gonzalez-Angulo AM, Akcakanat A, Liu S, Green MC, Murray JL, Chen H, Palla SL, Koenig KB, Brewster AM, Valero V, Ibrahim NK, Moulder-Thompson S, Litton JK, Tarco E, Moore J, Flores P, Crawford D, Dryden MJ, Symmans WF, Sahin A, Giordano SH, Pusztai L, Do K, Mills GB, Hortobagyi GN, Meric-Bernstam F. Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †. Annals Of Oncology 2014, 25: 1122-1127. PMID: 24669015, PMCID: PMC4037860, DOI: 10.1093/annonc/mdu124.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPathological complete responseStandard neoadjuvant chemotherapyNeoadjuvant chemotherapyReverse phase protein arrayBreast cancerPrimary triple-negative breast cancerMTOR pathwayReceptor-negative breast cancerTriple receptor-negative breast cancerAddition of everolimusGrade 3 pneumonitisGrade 3/4 stomatitisPI3K/AKT/mTOR pathwayRash/desquamationClinical response rateGrade 3/4 toxicitiesPhase II studyClinical end pointsCombination of paclitaxelAKT/mTOR pathwayDirect antiproliferative activityBreast cancer cellsDownregulation of mTORII studyMitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential
Pelicano H, Zhang W, Liu J, Hammoudi N, Dai J, Xu RH, Pusztai L, Huang P. Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential. Breast Cancer Research 2014, 16: 434. PMID: 25209360, PMCID: PMC4303115, DOI: 10.1186/s13058-014-0434-6.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateCell Line, TumorElectron Transport Chain Complex ProteinsEnergy MetabolismFemaleGlucoseGlutathioneHumansHydrocarbons, BrominatedLactic AcidMitochondriaNADPOxidation-ReductionOxygen ConsumptionPropionatesReactive Oxygen SpeciesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionTOR Serine-Threonine KinasesTriple Negative Breast NeoplasmsConceptsTNBC cellsBreast cancer cellsBreast cancerCancer cellsPositive cellsMetabolic alterationsIntroductionTriple-negative breast cancerMTOR pathwayEstrogen receptor-positive cellsER-positive cellsEffective therapeutic approachReceptor-positive cellsBreast cancer subtypesBreast cancer cell linesEffective therapeutic strategyTriple-negative breast cancer cell linesCurrent chemotherapeutic agentsMalignant breast cancerProfound metabolic alterationsHigher glucose uptakeInhibition of glycolysisCancer cell linesPoor prognosisLower mitochondrial respirationMitochondrial respiration
2010
Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer
Iwamoto T, Bianchini G, Qi Y, Cristofanilli M, Lucci A, Woodward WA, Reuben JM, Matsuoka J, Gong Y, Krishnamurthy S, Valero V, Hortobagyi GN, Robertson F, Symmans WF, Pusztai L, Ueno NT. Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer. Breast Cancer Research And Treatment 2010, 125: 785-795. PMID: 21153052, PMCID: PMC4109066, DOI: 10.1007/s10549-010-1280-6.Peer-Reviewed Original ResearchConceptsInflammatory breast cancerClinical subtypesBreast cancerNon-IBC patientsCase-control studyDistinct clinical subtypesDifferent molecular subtypesNon-IBC tumorsSignificant differencesNon-IBC specimensImmune system-related pathwaysLipid metabolism-related pathwaysHER2 statusReceptor phenotypeMetabolism-related pathwaysMolecular subtypesIBC tumorsSurvival curvesSubtypesTumor samplesHormone receptorsCancerPatientsT-testHER2PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer
Loi S, Haibe-Kains B, Majjaj S, Lallemand F, Durbecq V, Larsimont D, Gonzalez-Angulo AM, Pusztai L, Symmans WF, Bardelli A, Ellis P, Tutt AN, Gillett CE, Hennessy BT, Mills GB, Phillips WA, Piccart MJ, Speed TP, McArthur GA, Sotiriou C. PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 10208-10213. PMID: 20479250, PMCID: PMC2890442, DOI: 10.1073/pnas.0907011107.Peer-Reviewed Original ResearchMeSH KeywordsAntibiotics, AntineoplasticAntineoplastic Agents, HormonalBase SequenceBreast NeoplasmsCell Line, TumorClass I Phosphatidylinositol 3-KinasesDNA PrimersFemaleGene Expression ProfilingHumansMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesMutationNeoplasms, Hormone-DependentOligonucleotide Array Sequence AnalysisPhosphatidylinositol 3-KinasesPrognosisProteinsProto-Oncogene Proteins c-aktReceptor, ErbB-2Receptors, EstrogenSignal TransductionSirolimusTamoxifenTOR Serine-Threonine KinasesTranscription FactorsConceptsBreast cancerPIK3CA mutationsClinical outcomesEstrogen receptor-positive breast cancerReceptor-positive breast cancerGene signaturePIK3CA mutation statusPI3K/mTOR inhibitorBetter clinical outcomesPI3K/mTOR inhibitionHuman breast cancerBC cell linesPIK3CA mutant breast cancersCommon genetic aberrationsTamoxifen monotherapyBetter prognosisMTOR inhibitorsBetter outcomesMutation statusMTOR inhibitionPathway activationExperimental modelGenetic aberrationsPrognosisCell lines