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 featuresSpatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer
Page D, Broeckx G, Jahangir C, Verbandt S, Gupta R, Thagaard J, Khiroya R, Kos Z, Abduljabbar K, Haab G, Acs B, Akturk G, Almeida J, Alvarado‐Cabrero I, Azmoudeh‐Ardalan F, Badve S, Baharun N, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Bouchmaa N, Burgues O, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Portela F, Deman F, Demaria S, Dudgeon S, Elghazawy M, Ely S, Fernandez‐Martín C, Fineberg S, Fox S, Gallagher W, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hardas A, Hart S, Hartman J, 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, Vincent‐Salomon A, Salto‐Tellez M, Saltz J, Sayed S, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, 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, Adams S, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Salgado R, Stovgaard E. Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2023, 260: 514-532. PMID: 37608771, PMCID: PMC11288334, DOI: 10.1002/path.6165.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 patternsAssessmentLymphocytesBiomarkersThymidine 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 biomarkersImpact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.
Lambertini M, Ceppi M, Anderson R, Cameron D, Bruzzone M, Franzoi M, Massarotti C, El-Abed S, Wang Y, Lecocq C, Nuciforo P, Rolyance R, Pusztai L, Sohn J, Latocca M, Arecco L, Pistilli B, Ruddy K, Ballestrero A, Del Mastro L, Peccatori F, Partridge A, Saura C, Untch M, Piccart M, Di Cosimo S, de Azambuja E, Demeestere I. Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer. Journal Of The National Comprehensive Cancer Network 2023, 21: 33-41.e16. PMID: 36634607, DOI: 10.6004/jnccn.2022.7065.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyAMH levelsOvarian reserveWeekly paclitaxelAntimüllerian hormoneBreast cancerWeek 2HER2-positive early breast cancerHER2-positive breast cancerSubsequent ovarian functionAnti-HER2 agentsAnti-HER2 treatmentMedian AMH levelsEarly breast cancerTime of surgeryFrozen serum samplesBiomarker analysisNeoALTTO trialPotential gonadotoxicityPremenopausal womenMedian ageAMH valuesOvarian functionAMH declineGonadotoxicity
2022
Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm DL, Pusztai L. Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC. Clinical Cancer Research 2022, 28: 3720-3728. PMID: 35903931, PMCID: PMC9444984, DOI: 10.1158/1078-0432.ccr-22-0862.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsTriple-negative breast cancerNon-AA patientsEvent-free survivalPhase I/II clinical trialsClinical trialsNeoadjuvant chemotherapyOverall survivalAA patientsEarly-stage triple-negative breast cancerIncidence of irAEsPathologic complete response rateSignificant associationMultivariate logistic regression analysisTumor-infiltrating lymphocyte countsComplete response ratePrimary efficacy endpointPD-L1 statusProportional hazards modelLogistic regression analysisAfrican American womenEFS ratesNeoadjuvant immunotherapyEfficacy endpointAdverse events
2017
Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06)
Ponde N, Bradbury I, Lambertini M, Ewer M, Campbell C, Ameels H, Zardavas D, Di Cosimo S, Baselga J, Huober J, Izquierdo M, Fumagalli D, Bozovic-Spasojevic I, Maetens M, Harbeck N, Pusztai L, Berghorn M, Im YH, Borrego MR, Chen DR, Rodeheffer R, Piccart M, Suter T, de Azambuja E. Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06). Breast Cancer Research And Treatment 2017, 168: 631-638. PMID: 29280043, PMCID: PMC5843537, DOI: 10.1007/s10549-017-4628-3.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyNT-proBNPBiomarker elevationCardiac toxicityEarly predictorHER2-positive early-stage breast cancerEarly-stage breast cancerAnthracycline-naïve patientsEarly cardiac toxicityLevels of TnTNT-proBNP elevationBrain natriuretic peptideBreast cancer patientsNeoALTTO trialWeekly paclitaxelCardiac dysfunctionTreatment armsCardiac damageNatriuretic peptideCancer patientsCardiac biomarkersBreast cancerPatientsTroponin TAmino-terminal fragment
2016
Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis
Jiang T, Shi W, Wali VB, Pongor L, Li C, Lau R, Győrffy B, Lifton RP, Symmans WF, Pusztai L, Hatzis C. Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis. PLOS Medicine 2016, 13: e1002193. PMID: 27959926, PMCID: PMC5154510, DOI: 10.1371/journal.pmed.1002193.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPathologic complete responseMD Anderson Cancer CenterNegative breast cancerBreast cancerMutation burdenExtensive residual diseaseBetter survival outcomesBRCA deficiencyImmune cell activityAnderson Cancer CenterPredictor of chemosensitivityHigh mutation burdenWhole-exome sequencingACT chemotherapyMDACC cohortTNBC cohortNeoadjuvant chemotherapyCare chemotherapyTaxane chemotherapyCancer Genome AtlasComplete responseSuch patientsImproved survivalAggressive diseaseClinical Utility of Biomarker Tests in Decisions on Extended Endocrine Therapy
Sanft T, Pusztai L. Clinical Utility of Biomarker Tests in Decisions on Extended Endocrine Therapy. Journal Of Clinical Oncology 2016, 34: 3942-3943. PMID: 27551119, DOI: 10.1200/jco.2016.67.3285.Peer-Reviewed Original ResearchTesting Violations of the Exponential Assumption in Cancer Clinical Trials with Survival Endpoints
Han G, Schell MJ, Zhang H, Zelterman D, Pusztai L, Adelson K, Hatzis C. Testing Violations of the Exponential Assumption in Cancer Clinical Trials with Survival Endpoints. Biometrics 2016, 73: 687-695. PMID: 27669414, PMCID: PMC6093291, DOI: 10.1111/biom.12590.Peer-Reviewed Original ResearchQuantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer
Mani NL, Schalper KA, Hatzis C, Saglam O, Tavassoli F, Butler M, Chagpar AB, Pusztai L, Rimm DL. Quantitative assessment of the spatial heterogeneity of tumor-infiltrating lymphocytes in breast cancer. Breast Cancer Research 2016, 18: 78. PMID: 27473061, PMCID: PMC4966732, DOI: 10.1186/s13058-016-0737-x.Peer-Reviewed Original ResearchConceptsIntraclass correlation coefficientQuantitative immunofluorescenceBreast cancerSame cancerSingle biopsyMultiplexed quantitative immunofluorescenceTumor-infiltrating lymphocytesPotential predictive markerPrimary breast carcinomaCytokeratin-positive epithelial cellsCD20-positive lymphocytesCD8 levelsLymphocyte scoreQIF scoresLymphocyte countLymphocyte subpopulationsMultiple biopsiesSubpopulation countsPredictive markerPrognostic informationBreast carcinomaBiopsyB lymphocytesCD3Breast tumorsAssessing cost-utility of predictive biomarkers in oncology: a streamlined approach
Safonov A, Wang S, Gross CP, Agarwal D, Bianchini G, Pusztai L, Hatzis C. Assessing cost-utility of predictive biomarkers in oncology: a streamlined approach. Breast Cancer Research And Treatment 2016, 155: 223-234. PMID: 26749360, PMCID: PMC5990969, DOI: 10.1007/s10549-016-3677-3.Peer-Reviewed Original ResearchConceptsQuality-adjusted life yearsCost-effectiveness analysisPredictive biomarkersBiomarker-guided treatmentIncremental cost-effectiveness ratioHealth-related qualityTreatment costsCost-effectiveness ratioClinical outcomesClinical efficacyPrognostic biomarkerTraditional cost-effectiveness analysisBiomarker useLife yearsBiomarker valuesBiomarker prevalenceClinical literatureBiomarkersTreatmentState transition modelDecision analytic approachMedical utilityDecision analytic toolsCrizotinibHER2
2015
Standardization efforts enabling next-generation sequencing and microarray based biomarkers for precision medicine
Zheng Y, Qing T, Song Y, Zhu J, Yu Y, Shi W, Pusztai L, Shi L. Standardization efforts enabling next-generation sequencing and microarray based biomarkers for precision medicine. Biomarkers In Medicine 2015, 9: 1265-1272. PMID: 26502353, DOI: 10.2217/bmm.15.99.Peer-Reviewed Original Research
2011
Maximizing biomarker discovery by minimizing gene signatures
Chang C, Wang J, Zhao C, Fostel J, Tong W, Bushel PR, Deng Y, Pusztai L, Symmans WF, Shi T. Maximizing biomarker discovery by minimizing gene signatures. BMC Genomics 2011, 12: s6. PMID: 22369133, PMCID: PMC3287502, DOI: 10.1186/1471-2164-12-s5-s6.Peer-Reviewed Original Research
2010
Use of standard markers and incorporation of molecular markers into breast cancer therapy
Kaufmann M, Pusztai L, Members T. Use of standard markers and incorporation of molecular markers into breast cancer therapy. Cancer 2010, 117: 1575-1582. PMID: 21472705, DOI: 10.1002/cncr.25660.Peer-Reviewed Original ResearchConceptsFuture clinical trialsClinical trialsBreast cancerRoutine pathological evaluationBreast cancer managementCancer Research GroupBreast cancer therapyRoutine clinical decisionImportant therapeutic targetPredictive gene signaturesPathological evaluationPatient selectionConsensus recommendationsCancer managementHeterogeneous diseaseTherapeutic targetPredictive valueBreast pathologyClinical decisionDifferent subtypesGene signatureGenomic profilingClinical levelNew molecular markersOutcome prediction
2008
Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer
Wolff AC, Berry D, Carey LA, Colleoni M, Dowsett M, Ellis M, Garber JE, Mankoff D, Paik S, Pusztai L, Smith ML, Zujewski J. Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer. Journal Of Clinical Oncology 2008, 26: 806-813. PMID: 18258990, DOI: 10.1200/jco.2007.15.2983.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntineoplastic AgentsApoptosisBiomarkersBiomedical ResearchBreast NeoplasmsCell ProliferationEpidemiologic Research DesignErbB ReceptorsEthics, ClinicalFemaleGene Expression ProfilingHumansMastectomy, SegmentalNeoadjuvant TherapyPatient AdvocacyPreoperative CarePrognosisReceptors, SteroidTreatment OutcomeConceptsPreoperative systemic therapyOperable breast cancerSystemic therapyBreast cancerTrial designEnd pointCohesive multidisciplinary teamBreast conservation ratesEffective alternative therapyTrial end pointsLong-term outcomesSpecific breast cancer subtypesPredictors of responseNovel trial designsIntermediate end pointsBreast cancer subtypesIndividual patient subgroupsAdjuvant trialsPatient subgroupsSmall trialsAlternative therapiesMAIN OUTCOMEClinical careCancer subtypesMultidisciplinary team
2005
Pharmacogenomics and Clinical Biomarkers in Drug Discovery and Development
Ross JS, Symmans WF, Pusztai L, Hortobagyi GN. Pharmacogenomics and Clinical Biomarkers in Drug Discovery and Development. American Journal Of Clinical Pathology 2005, 124: s29-s41. PMID: 16468416, DOI: 10.1309/xyqafanapync6x59.Peer-Reviewed Original ResearchConceptsHuman genome sequenceGene expression profilesGenome sequenceEpigenetic eventsExpression profilesProteomics researchDrug discoveryRapid evolutionComputational biologyPharmaceutical industryMolecular diagnosticsDiscoveryFurther understandingBiosensorRNABiologyAnticancerSequenceClinical biomarkersAnti-inflammatory drugsDrug efficacyToxicityPrediction of responseDevelopmentContinuous technological advancementsMicrotubule-associated protein tau: A marker of paclitaxel sensitivity in breast cancer
Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, Ayers M, Ross JS, Zhang P, Buchholz TA, Kuerer H, Green M, Arun B, Hortobagyi GN, Symmans WF, Pusztai L. Microtubule-associated protein tau: A marker of paclitaxel sensitivity in breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 8315-8320. PMID: 15914550, PMCID: PMC1149405, DOI: 10.1073/pnas.0408974102.Peer-Reviewed Original ResearchConceptsPathologic complete responseBreast cancerBreast cancer cellsLow tau expressionPaclitaxel-containing chemotherapyCancer cellsLower mRNA expressionRegulation of tauPaclitaxel therapyComplete responseIndependent predictorsNuclear gradePaclitaxel sensitivityTau expressionTherapeutic strategiesStage IMultivariate analysisProtein tauTau proteinMRNA expressionTissue arraysDiagnostic testsPaclitaxelCancerChemotherapy