2024
Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations
Yasin F, Sokol E, Vasan N, Pavlick D, Huang R, Pelletier M, Levy M, Pusztai L, Lacy J, Zhang J, Ross J, Cecchini M. Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations. The Oncologist 2024, oyae259. PMID: 39401325, DOI: 10.1093/oncolo/oyae259.Peer-Reviewed Original ResearchAdvanced colorectal cancerPIK3CA mutationsColorectal cancerPI3K inhibitionPI3K inhibitorsBurden of colorectal cancerActivating mutationsResponse to PI3K inhibitionSensitive to PI3K inhibition.Foundation Medicine databaseMetastatic colorectal cancerClinically relevant mutationsMicrosatellite instability-highPI3K signalingTumor DNAPIK3CA variantsClinical carePIK3CA oncogeneClinical variablesE545KGenomic profilingPIK3CAE542KMedicine DatabasePatients
2023
Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy
Licata L, Barreca M, Galbardi B, Dugo M, Viale G, Győrffy B, Karn T, Pusztai L, Gianni L, Callari M, Bianchini G. Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy. British Journal Of Cancer 2023, 129: 2025-2033. PMID: 37935787, PMCID: PMC10703787, DOI: 10.1038/s41416-023-02477-7.Peer-Reviewed Original ResearchConceptsNeoadjuvant chemotherapyPoor prognosisBreast cancerTreatment responseHigher pathological complete response rateResponse rateHigh pathological response ratePathological complete response ratePathological response rateComplete response rateHigher proliferationHigh recurrence riskMolecular featuresEndocrine therapyLower ERHigh TMBDismal outcomePIK3CA mutationsMethodsGene expression dataClinical dataT cellsPotential therapyRecurrence riskTumorsUnique molecular features
2021
Targeted RNAseq assay incorporating unique molecular identifiers for improved quantification of gene expression signatures and transcribed mutation fraction in fixed tumor samples
Fu C, Marczyk M, Samuels M, Trevarton AJ, Qu J, Lau R, Du L, Pappas T, Sinn BV, Gould RE, Pusztai L, Hatzis C, Symmans WF. Targeted RNAseq assay incorporating unique molecular identifiers for improved quantification of gene expression signatures and transcribed mutation fraction in fixed tumor samples. BMC Cancer 2021, 21: 114. PMID: 33541297, PMCID: PMC7860187, DOI: 10.1186/s12885-021-07814-8.Peer-Reviewed Original ResearchConceptsPolymerase chain reactionParaffin-embedded tumor tissue samplesConcordance correlation coefficientFresh frozenFFPE samplesPrimary breast cancerMulti-gene signatureTumor tissue samplesActivating point mutationMutant allele fractionReverse transcriptionKey breast cancer genesGene expression signaturesBreast cancer genesPIK3CA mutationsBackgroundOur objectiveBreast cancerWhole transcriptome RNAseqTumor samplesLin's concordance correlation coefficientHormone receptorsFF samplesTissue samplesExpression signaturesChain reaction
2020
Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer
Huang RSP, Li X, Haberberger J, Sokol E, Severson E, Duncan DL, Hemmerich A, Edgerly C, Williams E, Elvin J, Vergilio J, Killian J, Lin D, Hiemenz M, Xiao J, McEwan D, Holmes O, Danziger N, Erlich R, Frampton G, Cohen M, McGregor K, Reddy P, Cardeiro D, Anhorn R, Venstrom J, Alexander B, Brown C, Pusztai L, Ross J, Ramkissoon S. Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer. The Oncologist 2020, 25: 943-953. PMID: 32869930, PMCID: PMC7648336, DOI: 10.1634/theoncologist.2020-0449.Peer-Reviewed Original ResearchConceptsComprehensive genomic profilingPD-L1 immunohistochemistryPotential therapeutic optionBreast cancerPD-L1Therapeutic optionsTriple negative breast cancer cohortDrug AdministrationHormone receptor-positive breast cancerReceptor-positive breast cancerGenomic profilingTriple-negative breast cancerPD-L1 positivityRoutine clinical careMutations/MbBreast cancer cohortBiomarker landscapeTNBC cohortNab-paclitaxelGermline testingConsecutive patientsReceptor negativeHER2-positiveClinical trialsPIK3CA mutations
2012
Use of next-generation sequencing (NGS) to detect high frequency of targetable alterations in primary and metastatic breast cancer (MBC).
Pusztai L, Yelensky R, Wang B, Avritscher R, Symmans W, Lipson D, Palmer G, Moulder S, Stephens P, Wu Y, Cronin M. Use of next-generation sequencing (NGS) to detect high frequency of targetable alterations in primary and metastatic breast cancer (MBC). Journal Of Clinical Oncology 2012, 30: 10559-10559. DOI: 10.1200/jco.2012.30.15_suppl.10559.Peer-Reviewed Original ResearchMetastatic breast cancerClinical trialsNext-generation sequencingNeedle biopsyBreast cancerGenomic alterationsClinical treatment optionsHER2 gene amplificationPatient selection approachAdjuvant therapyTargetable alterationsTreatment optionsPIK3CA mutationsNovel agentsERBB2 alterationsInvestigational drugsTherapeutic implicationsCancer-related genesBiopsyPredictive valueProspective testingNGS profilingDriver mutationsTherapyCancerMutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers
Santarpia L, Qi Y, Stemke-Hale K, Wang B, Young EJ, Booser DJ, Holmes FA, O’Shaughnessy J, Hellerstedt B, Pippen J, Vidaurre T, Gomez H, Valero V, Hortobagyi GN, Symmans WF, Bottai G, Di Leo A, Gonzalez-Angulo AM, Pusztai L. Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers. Breast Cancer Research And Treatment 2012, 134: 333-343. PMID: 22538770, PMCID: PMC3885980, DOI: 10.1007/s10549-012-2035-3.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast cancer subtypesBreast cancerPIK3CA mutationsCancer subtypesEstrogen receptor-positive cancersBreast cancer molecular subtypesMajor breast cancer subtypesSingle needle biopsyProspective clinical trialsReceptor-positive cancersDifferent breast cancer subtypesDifferent clinical subtypesNegative breast cancerCancer molecular subtypesFine-needle aspirationMutation patternsClinical subtypesClinical trialsNeedle biopsyMolecular subtypesNeedle aspirationInvestigational drugsStage IFBXW7 mutations
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
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
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
2008
An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, Symmans WF, Pusztai L, Nolden LK, Horlings H, Berns K, Hung MC, van de Vijver MJ, Valero V, Gray JW, Bernards R, Mills GB, Hennessy BT. An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer. Cancer Research 2008, 68: 6084-6091. PMID: 18676830, PMCID: PMC2680495, DOI: 10.1158/0008-5472.can-07-6854.Peer-Reviewed Original ResearchConceptsPIK3CA mutationsBreast cancerAKT1 mutationsPTEN lossPathway aberrationsHormone receptor-positive breast cancer patientsHormone receptor-positive breast cancerPTEN mutationsReceptor-positive breast cancer patientsHormone receptor-positive cancersPI3K pathway aberrationsCell linesReceptor-positive breast cancerAdjuvant tamoxifen therapyReceptor-positive cancersBreast cancer patientsDifferent breast cancer subtypesDownstream PI3K/AktBasal-like tumorsBreast cancer subtypesHuman breast cancerPI3K inhibitor LY294002PI3K/AktK inhibitor LY294002PI3K inhibitionPIK3CA-activating mutations and chemotherapy sensitivity in stage II–III breast cancer
Liedtke C, Cardone L, Tordai A, Yan K, Gomez HL, Figureoa LJ, Hubbard RE, Valero V, Souchon EA, Symmans WF, Hortobagyi GN, Bardelli A, Pusztai L. PIK3CA-activating mutations and chemotherapy sensitivity in stage II–III breast cancer. Breast Cancer Research 2008, 10: r27. PMID: 18371219, PMCID: PMC2397526, DOI: 10.1186/bcr1984.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnthracyclinesAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantClass I Phosphatidylinositol 3-KinasesDNA Mutational AnalysisFemaleHumansLymphatic MetastasisMiddle AgedMutationNeoadjuvant TherapyNeoplasm StagingPhosphatidylinositol 3-KinasesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTaxoidsConceptsPathological complete responseER-positive tumorsPIK3CA mutationsBreast cancerChemotherapy sensitivityPIK3CA exon 9 mutationsStage IIResidual cancer burden scoreER-negative breast tumorsReceptor expression statusNode-positive diseaseResultsTwenty-three patientsTaxane-based chemotherapyType of chemotherapyNode-positive tumorsPIK3CA-activating mutationsEstrogen receptor (ER) expression statusExon 9 mutationsPIK3CA activationRCB scoreChemotherapy regimenNeoadjuvant chemotherapyComplete responseResidual cancerER status