2018
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer
Dickler MN, Saura C, Richards DA, Krop IE, Cervantes A, Bedard PL, Patel MR, Pusztai L, Oliveira M, Cardenas AK, Cui N, Wilson TR, Stout TJ, Wei MC, Hsu JY, Baselga J. Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer. Clinical Cancer Research 2018, 24: 4380-4387. PMID: 29793946, PMCID: PMC6139036, DOI: 10.1158/1078-0432.ccr-18-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleFulvestrantHumansImidazolesMiddle AgedMutationOxazepinesReceptor, ErbB-2Receptors, EstrogenConceptsAdverse eventsClinical activityBreast cancerMutation statusOpen-label phase II studyHR-positive breast cancerHigher objective response rateConfirmatory phase III trialNCI CTCAE v4.0Median treatment durationObjective response ratePhase II studySerious adverse eventsNew safety signalsPhase III trialsPositive breast cancerClin Cancer ResIntramuscular fulvestrantMeasurable diseaseRECIST v1.1II studyIII trialsPostmenopausal womenUnacceptable toxicityTumor response
2014
TP53 mutation‐correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53‐mutated breast cancers
Győrffy B, Bottai G, Lehmann-Che J, Kéri G, Őrfi L, Iwamoto T, Desmedt C, Bianchini G, Turner NC, de Thè H, André F, Sotiriou C, Hortobagyi GN, Di Leo A, Pusztai L, Santarpia L. TP53 mutation‐correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53‐mutated breast cancers. Molecular Oncology 2014, 8: 508-519. PMID: 24462521, PMCID: PMC5528634, DOI: 10.1016/j.molonc.2013.12.018.Peer-Reviewed Original ResearchConceptsBreast cancerTP53 mutation statusPrognostic valueBC cellsMutation statusER-negative breast cancerDifferent BC cell linesFuture clinical trialsSignificant prognostic markerPotential therapeutic targetBC cell linesType of treatmentNeoadjuvant chemotherapyBC patientsClinical behaviorPrognostic markerClinical trialsConventional chemotherapyEstrogen receptorPotent small molecule inhibitorsTumor relapseSmall molecule inhibitorsTherapeutic targetClinical relevanceTP53 status
2012
Distinct tumor protein p53 mutants in breast cancer subgroups
Dumay A, Feugeas J, Wittmer E, Lehmann‐Che J, Bertheau P, Espié M, Plassa L, Cottu P, Marty M, André F, Sotiriou C, Pusztai L, de Thé H. Distinct tumor protein p53 mutants in breast cancer subgroups. International Journal Of Cancer 2012, 132: 1227-1231. PMID: 22886769, DOI: 10.1002/ijc.27767.Peer-Reviewed Original ResearchConceptsBasal tumorsLuminal tumorsMolecular apocrine tumoursDifferent breast cancer subtypesBreast cancer subgroupsBreast cancer subtypesP53 mutation statusApocrine tumorsTumor protein p53Molecular apocrineCancer subgroupsBreast cancerTP53 alterationsMutation statusBreast tumorsLoss of functionCancer subtypesTumorsComplex mutationsP53 gainHigh frequencyHigh rateDifferent functional consequencesMissense mutationsProtein p53
2011
Distinct p53 Gene Signatures Are Needed to Predict Prognosis and Response to Chemotherapy in ER-Positive and ER-Negative Breast Cancers
Coutant C, Rouzier R, Qi Y, Lehmann-Che J, Bianchini G, Iwamoto T, Hortobagyi GN, Symmans WF, Uzan S, Andre F, de Thé H, Pusztai L. Distinct p53 Gene Signatures Are Needed to Predict Prognosis and Response to Chemotherapy in ER-Positive and ER-Negative Breast Cancers. Clinical Cancer Research 2011, 17: 2591-2601. PMID: 21248301, DOI: 10.1158/1078-0432.ccr-10-1045.Peer-Reviewed Original ResearchConceptsER- cancersPredictive valueBreast cancerP53 signatureWorse distant metastasis-free survivalDistant metastasis-free survivalER-negative breast cancerAdjuvant tamoxifen therapyDifferent molecular subsetsMetastasis-free survivalDifferent prognostic valueNegative breast cancerHigher chemotherapy sensitivityTamoxifen therapyFree survivalBetter prognosisER-positivePoor prognosisPrognostic valuePrognostic markerMolecular subsetsChemotherapy sensitivityMutation statusP53 mutationsMultivariate analysis
2010
PIK3CA 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
2009
Clinical Subtype-Derived p53 Gene Signature Is Predictive of Prognosis and Response to Chemotherapy in ER-Positive but Not in ER-Negative Breast Cancers.
Pusztai L, Rouzier R, Qi Y, Lehmann-Che J, Bianchini G, Iwamoto T, Symmans W, Andre F, de The H, Coutant C, Coutant C. Clinical Subtype-Derived p53 Gene Signature Is Predictive of Prognosis and Response to Chemotherapy in ER-Positive but Not in ER-Negative Breast Cancers. Cancer Research 2009, 69: 6122-6122. DOI: 10.1158/0008-5472.sabcs-09-6122.Peer-Reviewed Original ResearchDistant metastasis-free survivalP53 signatureBreast cancerER- cancersPredictive valueWorse distant metastasis-free survivalSystemic adjuvant therapyER- breast cancerMetastasis-free survivalNegative breast cancerDifferent molecular subtypesP53 functional statusP53 gene mutationsGene expression-based predictorsP53 mutation statusAdjuvant tamoxifenAdjuvant therapyFree survivalBackgroundBreast cancerFunctional statusMolecular subtypesIndependent cohortNeoplastic diseaseChemotherapy sensitivityMutation statusCorrelation of PIK3CA mutation-associated gene expression signature (PIK3CA-GS) with deactivation of the PI3K pathway and with prognosis within the luminal-B ER+ breast cancers
Loi S, Haibe-Kains B, Lallemand F, Pusztai L, Bardelli A, Gillett C, Ellis P, Piccart-Gebhart M, Phillips W, McArthur G, Sotiriou C. Correlation of PIK3CA mutation-associated gene expression signature (PIK3CA-GS) with deactivation of the PI3K pathway and with prognosis within the luminal-B ER+ breast cancers. Journal Of Clinical Oncology 2009, 27: 533-533. DOI: 10.1200/jco.2009.27.15_suppl.533.Peer-Reviewed Original ResearchPI3K pathwayBreast cancerPIK3CA mutationsMutation statusGene expression signaturesK pathwayClinical outcomesLuminal B breast cancerLuminal BC subtypePIK3CA mutation statusBetter clinical outcomesIndependent prognostic informationB breast cancerExpression signaturesPI3K inhibitorsPI3K inhibitionBC cohortDistinct gene expression signaturesEndocrine therapyBC samplesBC subtypesPrognostic informationFavorable outcomeEstrogen receptorMutation carriers