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 DatabasePatientsDatopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial
Khoury K, Meisel J, Yau C, Rugo H, Nanda R, Davidian M, Tsiatis B, Chien A, Wallace A, Arora M, Rozenblit M, Hershman D, Zimmer A, Clark A, Beckwith H, Elias A, Stringer-Reasor E, Boughey J, Nangia C, Vaklavas C, Omene C, Albain K, Kalinsky K, Isaacs C, Tseng J, Roussos Torres E, Thomas B, Thomas A, Sanford A, Balassanian R, Ewing C, Yeung K, Sauder C, Sanft T, Pusztai L, Trivedi M, Outhaythip A, Li W, Onishi N, Asare A, Beineke P, Norwood P, Brown-Swigart L, Hirst G, Matthews J, Moore B, Fraser Symmans W, Price E, Beedle C, Perlmutter J, Pohlmann P, Shatsky R, DeMichele A, Yee D, van ‘t Veer L, Hylton N, Esserman L. Datopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial. Nature Medicine 2024, 1-9. PMID: 39277671, DOI: 10.1038/s41591-024-03266-2.Peer-Reviewed Original ResearchBreast cancerLikelihood of pathologic complete responseTreatment strategiesPathologic complete response rateEarly-stage breast cancerEarly surgical resectionTaxane-based regimenComplete response ratePathological complete responsePhase 2 trialBreast cancer subtypesEffective personalized treatmentHigh-risk stageMagnetic resonance imagingComplete responseDoxorubicin-cyclophosphamideNeoadjuvant treatmentSurgical resectionOcular eventsEfficacy analysisPrimary endpointTumor subtypesNew agentsCancer subtypesPatientsAcademic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer
Kok M, Gielen R, Adams S, Lennerz J, Sharma P, Loibl S, Reardon E, Sonke G, Linn S, Delaloge S, Lacombe D, Robinson T, Badve S, Martin M, Balko J, Ignatiadis M, Curigliano G, Wolff A, Mittendorf E, Loi S, Pusztai L, Tolaney S, Salgado R. Academic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2024, 42: 3523-3529. PMID: 39038259, DOI: 10.1200/jco.24.00372.Peer-Reviewed Original ResearchNavigating practical challenges in immunotherapy for metastatic triple negative breast cancer
Licata L, Dieci M, De Angelis C, Marchiò C, Miglietta F, Cortesi L, Fabi A, Schmid P, Cortes J, Pusztai L, Bianchini G, Curigliano G. Navigating practical challenges in immunotherapy for metastatic triple negative breast cancer. Cancer Treatment Reviews 2024, 128: 102762. PMID: 38776613, DOI: 10.1016/j.ctrv.2024.102762.Peer-Reviewed Original ResearchTriple-negative breast cancerBreast cancerMetastatic triple negative breast cancerManagement of breast cancer patientsTriple negative breast cancerApproval of immunotherapyImmune checkpoint inhibitorsNegative breast cancerBreast cancer patientsEveryday clinical practiceCheckpoint inhibitorsTumor typesCancer patientsClinical trialsCancer therapyImmunotherapyCancerClinical practicePositive resultsCliniciansTumorTherapyPatientsTrialsInhibitors2LBA LBA Oral Immune subtyping in the Response Predictive Subtypes (RPS) identifies a subset of triple negative (TN) early-stage breast cancer patients with a very low likelihood of response to neoadjuvant immunotherapy (IO): results from 5 IO arms of the I-SPY2 TRIAL
Wolf D, Yau C, Haan J, Wehkamp D, Witteveen A, Glas A, Campbell M, Nanda R, Chien J, Shatsky R, Isaacs C, Barcura A, Mittempergher L, Kuilman M, Yee D, DeMichele A, Perlmutter J, Pusztai L, Esserman L, van ’t Veer L. 2LBA LBA Oral Immune subtyping in the Response Predictive Subtypes (RPS) identifies a subset of triple negative (TN) early-stage breast cancer patients with a very low likelihood of response to neoadjuvant immunotherapy (IO): results from 5 IO arms of the I-SPY2 TRIAL. European Journal Of Cancer 2024, 200: 113953. DOI: 10.1016/j.ejca.2024.113953.Peer-Reviewed Original Research
2023
Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer
Coman M, Pusztai L, Hooley R, Andreveja L, Kim L, Joshi N, Bersenev A, Krause D, Park T. Core Needle Biopsies as an Alternative Source for Ex Vivo Expanded TIL for Adoptive Cell Therapy in Triple-Negative Breast Cancer. Journal Of Immunotherapy 2023, 47: 49-53. PMID: 37991241, DOI: 10.1097/cji.0000000000000495.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesCore needle biopsyTriple-negative breast cancerNeedle biopsyBreast cancerEx vivoT-cell receptor clonalityUltrasound-guided core needle biopsyTriple negative breast cancer tumorsMorbidity of surgeryAdoptive cell therapyBreast cancer tumorsTIL generationAdoptive transferTIL culturesMultiple lesionsCytokine secretionMetastatic cancerSame patientTumor tissueCell therapyPatientsCancer tumorsCancerSurgeryLBA20 A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC)
Loi S, Curigliano G, Salgado R, Diaz R, Delaloge S, Rojas C, Kok M, Manich C, Harbeck N, Mittendorf E, Yardley D, Pusztai L, Zaizar A, Ungureanu A, Ades F, Chandra R, Nathani R, Pacius M, Wu J, McArthur H. LBA20 A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC). Annals Of Oncology 2023, 34: s1259-s1260. DOI: 10.1016/j.annonc.2023.10.010.Peer-Reviewed Original ResearchAssociations amongst genes, molecules, cells, and organs in breast cancer metastasis
Nathanson S, Dieterich L, Zhang X, Chitale D, Pusztai L, Reynaud E, Wu Y, Ríos-Hoyo A. Associations amongst genes, molecules, cells, and organs in breast cancer metastasis. Clinical & Experimental Metastasis 2023, 41: 417-437. PMID: 37688650, DOI: 10.1007/s10585-023-10230-w.Peer-Reviewed Original ResearchBreast cancer metastasisBreast cancerCancer metastasisOutcomes of patientsAnti-tumor immunityHope of cureAggressive therapyMultiple metastasesAggressive treatmentBone metastasesLymph nodesSystemic metastasesMorphologic subtypesClinical oncologistsMetastasisInternal visceraAssists cliniciansLymphatic endothelial cellsPatientsEndothelial cellsHealth SymposiumBasic scientistsMolecular expressionCancerMolecular aspectsMolecular Characterization of HER2-Low Invasive Breast Carcinoma by Quantitative RT-PCR Using Oncotype DX Assay
Lin H, Can T, Kahn A, Flannery C, Hoag J, Akkunuri A, Bailey H, Baehner R, Pusztai L, Rozenblit M. Molecular Characterization of HER2-Low Invasive Breast Carcinoma by Quantitative RT-PCR Using Oncotype DX Assay. The Oncologist 2023, 28: e973-e976. PMID: 37656608, PMCID: PMC10546821, DOI: 10.1093/oncolo/oyad249.Peer-Reviewed Original ResearchConceptsHER2 mRNA levelsIHC 0MRNA levelsOncotype DX recurrence score resultsEstrogen receptor-positive breast cancerReceptor-positive breast cancerCurrent adjuvant chemotherapyOncotype DX assayRecurrence Score resultsPositive breast cancerInvasive breast carcinomaIHC score 0Adjuvant chemotherapyQuantitative RT-PCRBreast carcinomaPositive statusScore 0Breast cancerStage IYale cohortHigher mRNA levelsCancerRT-PCRPatientsHER2Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226
Rutherford D, Medley S, Henderson N, Gersch C, Vandenberg T, Albain K, Dakhil S, Tirumali N, Gralow J, Hortobagyi G, Pusztai L, Mehta R, Hayes D, Kidwell K, Henry N, Barlow W, Rae J, Hertz D. Effects of CYP3A4 and CYP2C9 genotype on systemic anastrozole and fulvestrant concentrations in SWOG S0226. Pharmacogenomics 2023, 24: 665-673. PMID: 37615099, PMCID: PMC10565537, DOI: 10.2217/pgs-2023-0097.Peer-Reviewed Original ResearchPitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer
Thagaard J, Broeckx G, Page D, Jahangir C, Verbandt S, Kos Z, Gupta R, Khiroya R, Abduljabbar K, Haab G, Acs B, Akturk G, Almeida J, Alvarado‐Cabrero I, Amgad M, Azmoudeh‐Ardalan F, Badve S, Baharun N, Balslev E, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Bouchmaa N, Burgues O, Chardas A, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Dahl A, Portela F, Deman F, Demaria S, Hansen J, Dudgeon S, Ebstrup T, Elghazawy M, Fernandez‐Martín C, Fox S, Gallagher W, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hart S, Hartman J, Hauberg S, Hewitt S, Hida A, Horlings H, Husain Z, Hytopoulos E, Irshad S, Janssen E, Kahila M, Kataoka T, Kawaguchi K, Kharidehal D, Khramtsov A, Kiraz U, Kirtani P, Kodach L, Korski K, Kovács A, Laenkholm A, Lang‐Schwarz C, Larsimont D, Lennerz J, Lerousseau M, Li X, Ly A, Madabhushi A, Maley S, Narasimhamurthy V, Marks D, McDonald E, Mehrotra R, Michiels S, Minhas F, Mittal S, Moore D, Mushtaq S, Nighat H, Papathomas T, Penault‐Llorca F, Perera R, Pinard C, Pinto‐Cardenas J, Pruneri G, Pusztai L, Rahman A, Rajpoot N, Rapoport B, Rau T, Reis‐Filho J, Ribeiro J, Rimm D, Roslind A, Vincent‐Salomon A, Salto‐Tellez M, Saltz J, Sayed S, Scott E, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, Fineberg S, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson E, Tramm T, Tran W, van der Laak J, van Diest P, Verghese G, Viale G, Vieth M, Wahab N, Walter T, Waumans Y, Wen H, Yang W, Yuan Y, Zin R, Adams S, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Salgado R, Stovgaard E. Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2023, 260: 498-513. PMID: 37608772, PMCID: PMC10518802, DOI: 10.1002/path.6155.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesTriple-negative breast cancerBreast cancerTIL assessmentHER2-positive breast cancerRoutine clinical managementTIL evaluationTumor-immune interactionsClinical managementDiscordant assessmentsClinical significancePrognostic biomarkerTIL quantificationCancerDaily practicePatientsTrialsTissue patternsAssessmentLymphocytesBiomarkersPersistence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor-positive (HR +) breast cancer
Foldi J, Tsagianni A, Salganik M, Schnabel C, Brufsky A, van Londen G, Pusztai L, Sanft T. Persistence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor-positive (HR +) breast cancer. BMC Cancer 2023, 23: 606. PMID: 37391697, PMCID: PMC10314405, DOI: 10.1186/s12885-023-11104-w.Peer-Reviewed Original ResearchConceptsAdjuvant endocrine therapyEarly-stage hormone receptor-positive breast cancerHormone receptor-positive breast cancerReceptor-positive breast cancerEndocrine therapyBreast cancerLate breast cancer recurrenceExtended endocrine therapyNon-persistence ratesIntolerable side effectsBone density scanBreast cancer recurrenceHigher likelihoodRate of persistenceElectronic health recordsConclusionsIn patientsMedication persistenceTreatment persistenceLow patientsMetastatic recurrenceCancer recurrenceCommon reasonSide effectsPatientsStage IBPI23-012: Real-World Frequency of ECHO Monitoring and Incidence of Anti-HER2 Therapy Related Cardiac Events in HER2+ Breast Cancer Patients
Hood A, Mukallari B, Majeski J, Pusztai L, Adelson K, Amin K. BPI23-012: Real-World Frequency of ECHO Monitoring and Incidence of Anti-HER2 Therapy Related Cardiac Events in HER2+ Breast Cancer Patients. Journal Of The National Comprehensive Cancer Network 2023, 21: bpi23-012. DOI: 10.6004/jnccn.2022.7224.Peer-Reviewed Original ResearchThymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226)
Bergqvist M, Nordmark A, Williams A, Paoletti C, Barlow W, Cobain E, Mehta R, Gralow J, Hortobagyi G, Albain K, Pusztai L, Sharma P, Godwin A, Thompson A, Hayes D, Rae J. Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226). Biomarkers 2023, 28: 313-322. PMID: 36647745, PMCID: PMC10681159, DOI: 10.1080/1354750x.2023.2168063.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerNegative predictive valueEndocrine therapyThymidine kinase activityLower riskSingle-agent endocrine therapyMetastatic breast cancer patientsLonger progression-free survivalHigh negative predictive valueProgression-free survivalBreast cancer patientsSerum thymidine kinase activityAdditional therapyOverall survivalSuch patientsCancer patientsBlood drawEarly progressionDisease progressionRapid progressionBreast cancerPatientsSubsequent timepointsPredictive valuePotential biomarkersEvaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial
Speers C, Symmans W, Barlow W, Trevarton A, The S, Du L, Rae J, Shak S, Baehner R, Sharma P, Pusztai L, Hortobagyi G, Hayes D, Albain K, Godwin A, Thompson A. Evaluation of the Sensitivity to Endocrine Therapy Index and 21-Gene Breast Recurrence Score in the SWOG S8814 Trial. Journal Of Clinical Oncology 2023, 41: 1841-1848. PMID: 36649570, PMCID: PMC10082279, DOI: 10.1200/jco.22.01499.Peer-Reviewed Original ResearchConceptsBreast Recurrence ScoreAnthracycline-based chemotherapyDisease-free survivalRecurrence scoreEndocrine therapyTherapy indexAdjuvant anthracycline-based chemotherapyNode-positive breast cancerAdjuvant endocrine therapyPrimary end pointSubset of patientsPostmenopausal patientsChemotherapy benefitTreatment armsPrognostic indexPrognostic informationBreast cancerPrognostic assessmentPrognostic performancePatientsEnd pointTumor samplesChemotherapyClinical validationProportional hazards assumptionTumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer
Nanou A, Miao J, Coumans F, Dolce E, Darga E, Barlow W, Smerage J, Paoletti C, Godwin A, Pusztai L, Sharma P, Thompson A, Hortobagyi G, Terstappen L, Hayes D. Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer. JCO Precision Oncology 2023, 7: e2200372. PMID: 36634296, PMCID: PMC9928629, DOI: 10.1200/po.22.00372.Peer-Reviewed Original ResearchConceptsCycles of chemotherapyMetastatic breast cancerTumor-derived extracellular vesiclesOverall survivalBreast cancerTumor cellsExtracellular vesiclesComplementary prognostic factorComplementary prognostic valuePoor overall survivalAdditional prognostic biomarkerLonger OSPrognostic factorsPrognostic significanceCTC countPrognostic valuePrognostic biomarkerChemotherapyCancerPatientsCTCsCellsBiomarkers
2022
A preliminary, prospective study of peripheral neuropathy and cognitive function in patients with breast cancer during taxane therapy
Ibrahim EY, Munshani S, Domenicano I, Rodwin R, Nowak RJ, Pusztai L, Lustberg M, Ehrlich BE. A preliminary, prospective study of peripheral neuropathy and cognitive function in patients with breast cancer during taxane therapy. PLOS ONE 2022, 17: e0275648. PMID: 36206298, PMCID: PMC9543876, DOI: 10.1371/journal.pone.0275648.Peer-Reviewed Original ResearchConceptsNeurological side effectsSide effectsBreast cancerTaxane exposureProgressive neurological changesTaxane-based chemotherapyNon-interventional studyWeeks of treatmentEnd of treatmentIrreversible side effectsCourse of treatmentQuality of lifeTaxane therapyPeripheral neuropathyProspective studyPeripheral bloodBlood levelsCancer survivalNeuronal viabilityNeurological changesEffective treatmentChemotherapyCognitive impairmentPatientsPotential protein biomarkersTumor immune microenvironment of self-identified African American and non-African American triple negative breast cancer
Marczyk M, Qing T, O’Meara T, Yagahoobi V, Pelekanou V, Bai Y, Reisenbichler E, Cole KS, Li X, Gunasekharan V, Ibrahim E, Fanucci K, Wei W, Rimm DL, Pusztai L, Blenman KRM. Tumor immune microenvironment of self-identified African American and non-African American triple negative breast cancer. Npj Breast Cancer 2022, 8: 88. PMID: 35869114, PMCID: PMC9307813, DOI: 10.1038/s41523-022-00449-3.Peer-Reviewed Original ResearchTumor immune microenvironmentImmune microenvironmentTriple-negative breast cancer tissuesTriple-negative breast cancerAfrican AmericansImmune checkpoint inhibitorsTumor mutation burdenNegative breast cancerBreast cancer tissuesImmune-related pathwaysStromal TILsCheckpoint inhibitorsImmune exclusionClinical outcomesPD-L1Self-identified African AmericansCancer patientsImmune infiltrationBreast cancerMutation burdenCancer tissuesPredictive signatureMRNA expressionTherapeutic agentsPatients2MO Development of a prognostic gene-expression signature for early stage HER2-positive breast cancer patients
Di Cosimo S, Ciniselli C, Sotiriou C, Pogue-Geile K, Fumagalli D, de Azambuja E, Venet D, De Cecco L, Pong N, Cappelletti V, Tagliabue E, Wang Y, Manich C, Nuciforo P, Kuemmel S, Pusztai L, Daidone M, Pizzamiglio S, Pruneri G, Verderio P. 2MO Development of a prognostic gene-expression signature for early stage HER2-positive breast cancer patients. Annals Of Oncology 2022, 33: s124. DOI: 10.1016/j.annonc.2022.03.017.Peer-Reviewed Original ResearchExamination of Low ERBB2 Protein Expression in Breast Cancer Tissue
Fernandez AI, Liu M, Bellizzi A, Brock J, Fadare O, Hanley K, Harigopal M, Jorns JM, Kuba MG, Ly A, Podoll M, Rabe K, Sanders MA, Singh K, Snir OL, Soong TR, Wei S, Wen H, Wong S, Yoon E, Pusztai L, Reisenbichler E, Rimm DL. Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. JAMA Oncology 2022, 8: 1-4. PMID: 35113160, PMCID: PMC8814969, DOI: 10.1001/jamaoncol.2021.7239.Peer-Reviewed Original ResearchConceptsBreast cancer biopsiesT-DXdCancer biopsiesLarge randomized clinical trialsRandomized clinical trialsERBB2 protein expressionCentral pathology laboratoryBreast cancer tissuesAmerican Pathologists surveysStudy of concordanceTrastuzumab deruxtecanERBB2 positivityPatient populationClinical trialsScore 0Breast cancerImmunohistochemistry scoreCancer tissuesIHC assaysPatientsPathology laboratoryProtein expressionBiopsyIHCConcordance