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 featuresDual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency
Stecklein S, Barlow W, Pusztai L, Timms K, Kennedy R, Logan G, Seitz R, Badve S, Gökmen-Polar Y, Porter P, Linden H, Tripathy D, Hortobagyi G, Godwin A, Thompson A, Hayes D, Sharma P. Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency. JCO Precision Oncology 2023, 7: e2300197. PMID: 37972336, PMCID: PMC10681491, DOI: 10.1200/po.23.00197.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerHomologous recombination deficiencyBreast cancerAdjuvant anthracycline-based chemotherapyTherapeutic vulnerabilitiesRecombination deficiencyDistinct therapeutic vulnerabilitiesAnthracycline-based chemotherapyImmune response signaturesDNA-damaging therapiesFavorable prognosisIntermediate prognosisWorse prognosisImmunologic microenvironmentImmune responseChemoresistant tumorsPrognostic classificationHeterogeneous diseasePrognosisHeterogeneous groupDistinct subgroupsTumorsCancerResponse signatureSimultaneous assessmentSpatial 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 Research
2022
Prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer (SWOG S0800) using image analysis-based tumor infiltrating lymphocyte measurements.
Blenman K, Fanucci K, Bai Y, Pelekanou V, Nahleh Z, Shafi S, Burela S, Barlow W, Sharma P, Thompson A, Godwin A, Rimm D, Hortobagyi G, Pusztai L. Prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer (SWOG S0800) using image analysis-based tumor infiltrating lymphocyte measurements. Journal Of Clinical Oncology 2022, 40: 594-594. DOI: 10.1200/jco.2022.40.16_suppl.594.Peer-Reviewed Original ResearchPathologic complete responseBreast cancerNeoadjuvant chemotherapyComplete responseTIL scoreResidual diseaseResponse predictive markersBetter EFSBevacizumab benefitLymphocyte measurementsTIL assessmentFree survivalPredictive markerTIL quantificationInternational guidelinesPretreatment samplesLogistic regressionCancerOutcome discriminationChemotherapyScoresContinuous scoresTumorsClinical adoptionStrong positive correlation
2021
Diverse immune response of DNA damage repair-deficient tumors
Qing T, Jun T, Lindblad KE, Lujambio A, Marczyk M, Pusztai L, Huang KL. Diverse immune response of DNA damage repair-deficient tumors. Cell Reports Medicine 2021, 2: 100276. PMID: 34095878, PMCID: PMC8149377, DOI: 10.1016/j.xcrm.2021.100276.Peer-Reviewed Original ResearchConceptsCancer typesDDR-deficient tumorsImmune checkpoint inhibitorsHigh neoantigen loadDifferent immune phenotypesDiverse immune responsesAdaptive immune markersRepair-deficient tumorsDDR deficiencyCheckpoint inhibitorsImmunotherapy outcomesDNA damage repair deficiencyImmune infiltratesImmune markersNeoantigen loadSurvival outcomesImmune phenotypeTumor neoantigensImmune responseAnimal modelsGenomic biomarkersGermline mutationsPathway mutationsTumorsRepair deficiency
2020
Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Kos Z, Roblin E, Kim RS, Michiels S, Gallas BD, Chen W, van de Vijver KK, Goel S, Adams S, Demaria S, Viale G, Nielsen TO, Badve SS, Symmans WF, Sotiriou C, Rimm DL, Hewitt S, Denkert C, Loibl S, Luen SJ, Bartlett JMS, Savas P, Pruneri G, Dillon DA, Cheang MCU, Tutt A, Hall JA, Kok M, Horlings HM, Madabhushi A, van der Laak J, Ciompi F, Laenkholm AV, Bellolio E, Gruosso T, Fox SB, Araya JC, Floris G, Hudeček J, Voorwerk L, Beck AH, Kerner J, Larsimont D, Declercq S, Van den Eynden G, Pusztai L, Ehinger A, Yang W, AbdulJabbar K, Yuan Y, Singh R, Hiley C, Bakir MA, Lazar AJ, Naber S, Wienert S, Castillo M, Curigliano G, Dieci MV, André F, Swanton C, Reis-Filho J, Sparano J, Balslev E, Chen IC, Stovgaard EIS, Pogue-Geile K, Blenman KRM, Penault-Llorca F, Schnitt S, Lakhani SR, Vincent-Salomon A, Rojo F, Braybrooke JP, Hanna MG, Soler-Monsó MT, Bethmann D, Castaneda CA, Willard-Gallo K, Sharma A, Lien HC, Fineberg S, Thagaard J, Comerma L, Gonzalez-Ericsson P, Brogi E, Loi S, Saltz J, Klaushen F, Cooper L, Amgad M, Moore DA, Salgado R. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. Npj Breast Cancer 2020, 6: 17. PMID: 32411819, PMCID: PMC7217863, DOI: 10.1038/s41523-020-0156-0.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesEarly TNBCBreast cancerHER2-positive breast cancerTumor-infiltrating lymphocytesLymphocyte distributionStromal tumorsInflammatory cellsPredictive biomarkersTreatment selectionPrognostic toolClinical practiceOutcome estimatesLymphocytesReproducible assessmentTNBCTumorsCancerScoring guidelinesMultiple areasTumor boundariesRisk estimationImpact of discrepanciesRing studiesAssessment
2019
Quantitative MHC II protein expression levels in tumor epithelium to predict response to the PD1 inhibitor pembrolizumab in the I-SPY 2 Trial.
Wulfkuhle J, Yau C, Wolf D, Gallagher R, Brown Swigart L, Hirst G, Campbell M, Nanda R, Liu M, Pusztai L, Esserman L, Berry D, van 't Veer L, Petricoin E. Quantitative MHC II protein expression levels in tumor epithelium to predict response to the PD1 inhibitor pembrolizumab in the I-SPY 2 Trial. Journal Of Clinical Oncology 2019, 37: 2631-2631. DOI: 10.1200/jco.2019.37.15_suppl.2631.Peer-Reviewed Original ResearchI-SPY 2 TRIALImmune checkpoint inhibitorsCheckpoint inhibitorsTumor epitheliumPD1 inhibitor pembrolizumabTumor antigen presentationHER2-negative subtypeMHC-II expressionTumor cell expressionPredictors of responseWilcoxon rank sum testPositive associationRank sum testProtein expression levelsImmune activationControl armAntigen presentationResponse predictorsHR subgroupsB cellsCell expressionPatientsSum testProtein expressionTumorsA prospective decision-impact study incorporating Breast Cancer Index into extended endocrine therapy decision-making
Sanft T, Berkowitz A, Schroeder B, Hatzis C, Schnabel C, Brufsky A, Gustavsen G, Pusztai L, Londen G. A prospective decision-impact study incorporating Breast Cancer Index into extended endocrine therapy decision-making. Breast Cancer Management 2019, 8: bmt22. DOI: 10.2217/bmt-2019-0001.Peer-Reviewed Original Research
2018
286PD Post-treatment biopsies show evidence of cell cycle arrest and immune cell infiltration into tumors of ladiratuzumab vedotin-treated advanced breast cancer patients
Specht J, Pusztai L, Forero-Torres A, Mita M, Weise A, Krop I, Grosse-Wilde A, Wang Z, Li M, Hengel S, Garfin P, Means G, Onsum M, Modi S. 286PD Post-treatment biopsies show evidence of cell cycle arrest and immune cell infiltration into tumors of ladiratuzumab vedotin-treated advanced breast cancer patients. Annals Of Oncology 2018, 29: viii92. DOI: 10.1093/annonc/mdy272.278.Peer-Reviewed Original Research
2017
Effects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial.
Pelekanou V, Barlow W, von Wahlde M, Wasserman B, Lo Y, Hayes D, Hortobagyi G, Gralow J, Tripathy D, Livingston R, Porter P, Nahleh Z, Rimm D, Pusztai L. Effects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial. Journal Of Clinical Oncology 2017, 35: 519-519. DOI: 10.1200/jco.2017.35.15_suppl.519.Peer-Reviewed Original ResearchPD-L1 expressionNeoadjuvant chemotherapyNAC armTIL countClinical trialsImmune parametersNAC samplesBaseline PD-L1 expressionPathologic complete response rateDose-dense doxorubicinComplete response ratePD-L1 immunohistochemistryHER2-negative casesMinority of casesNab-paclitaxelResidual diseaseMean changeResponse rateLogistic regressionTILsBaselineEpithelial cellsHigh PCRChemotherapyTumorsPhylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations
Brown D, Smeets D, Székely B, Larsimont D, Szász AM, Adnet PY, Rothé F, Rouas G, Nagy ZI, Faragó Z, Tőkés AM, Dank M, Szentmártoni G, Udvarhelyi N, Zoppoli G, Pusztai L, Piccart M, Kulka J, Lambrechts D, Sotiriou C, Desmedt C. Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations. Nature Communications 2017, 8: 14944. PMID: 28429735, PMCID: PMC5474888, DOI: 10.1038/ncomms14944.Peer-Reviewed Original ResearchConceptsDistant metastasisPrimary tumorClonal frequency analysisMultiple metastatic lesionsBreast cancer disseminationBreast cancer progressionSomatic mutationsWhole-exome sequencingAvailable metastasesMetastatic lesionsMetastatic precursorsPrimary lesionMetastatic tumorsDisease progressionBreast cancerPatterns of disseminationMetastasisMetastatic progressionCancer disseminationPatientsCancer progressionCopy number profilingCopy number aberrationsTumorsMonoclonal origin
2016
Patient preferences regarding incidental genomic findings discovered during tumor profiling
Yushak ML, Han G, Bouberhan S, Epstein L, DiGiovanna MP, Mougalian SS, Sanft TB, Abu-Khalaf MM, Chung GG, Stein SM, Goldberg SB, Pusztai L, Hofstatter EW. Patient preferences regarding incidental genomic findings discovered during tumor profiling. Cancer 2016, 122: 1588-1597. PMID: 26970385, DOI: 10.1002/cncr.29951.Peer-Reviewed Original ResearchConceptsIncidental findingTumor profilingGermline variantsAmbulatory oncology clinicsMajority of patientsStandard of careTumor profiling testsOncology clinicPreventable diseaseFamily historyPatient tumorsInformation patientsPreventable illnessPatientsDisease variablesUnpreventable diseaseUncertain significanceDisclosure preferencesCancerFrequent concernTumorsIllnessProfiling testsDiseaseCurrent study
2015
Reproducibility of homologous recombination deficiency (HRD) scores in biopsies of triple negative breast cancer (TNBC) tumors.
Timms K, Chagpar A, Wali V, Bossuyt V, Reid J, Gutin A, Neff C, Hofstatter E, Lanchbury J, Pusztai L. Reproducibility of homologous recombination deficiency (HRD) scores in biopsies of triple negative breast cancer (TNBC) tumors. Journal Of Clinical Oncology 2015, 33: 1091-1091. DOI: 10.1200/jco.2015.33.15_suppl.1091.Peer-Reviewed Original Research
2014
Pilot study of sorafenib and biweekly capecitabine in patients with advanced breast and gastrointestinal tumors.
Jhaveri A, Abu-Khalaf M, DiGiovanna M, Pusztai L, Hofstatter E, Sanft T, Sowers N, Lurie B, Silber A, Brandt D, Hochster H, Lacy J, Stein S, Chung G. Pilot study of sorafenib and biweekly capecitabine in patients with advanced breast and gastrointestinal tumors. Journal Of Clinical Oncology 2014, 32: 2561-2561. DOI: 10.1200/jco.2014.32.15_suppl.2561.Peer-Reviewed Original Research
2013
Genome-wide gene expression profiling to predict resistance to anthracyclines in breast cancer patients
Haibe-Kains B, Desmedt C, Di Leo A, Azambuja E, Larsimont D, Selleslags J, Delaloge S, Duhem C, Kains JP, Carly B, Maerevoet M, Vindevoghel A, Rouas G, Lallemand F, Durbecq V, Cardoso F, Salgado R, Rovere R, Bontempi G, Michiels S, Buyse M, Nogaret JM, Qi Y, Symmans F, Pusztai L, D'Hondt V, Piccart-Gebhart M, Sotiriou C. Genome-wide gene expression profiling to predict resistance to anthracyclines in breast cancer patients. Data In Brief 2013, 1: 7-10. PMID: 26484051, PMCID: PMC4608867, DOI: 10.1016/j.gdata.2013.09.001.Peer-Reviewed Original ResearchBreast cancer patientsResponse/resistanceAnthracycline monotherapyNeoadjuvant trialsGene expression signaturesNegative tumorsCancer patientsBreast cancerClinical dataEstrogen receptorClinical OncologyPredictive valuePatientsAnthracyclinesGene expressionII alphaExpression signaturesGenome-wide gene expressionMonotherapyExpressionTumorsCancerOncologyTrialsBiomarkersConcordance Between CYP2D6 Genotypes Obtained From Tumor-Derived and Germline DNA
Rae JM, Regan MM, Thibert JN, Gersch C, Thomas D, Leyland-Jones B, Viale G, Pusztai L, Hayes DF, Skaar T, Van Poznak C. Concordance Between CYP2D6 Genotypes Obtained From Tumor-Derived and Germline DNA. Journal Of The National Cancer Institute 2013, 105: 1332-1334. PMID: 23958736, PMCID: PMC3888280, DOI: 10.1093/jnci/djt204.Peer-Reviewed Original ResearchConceptsCYP2D6 genotypeCYP2D6 metabolic phenotypeBreast cancer patientsMetabolic phenotypeAnti-estrogen tamoxifenCancer clinical trialsCancer patientsClinical trialsTumor alterationsGermline DNAConflicting resultsPatientsTumorsTissue sourcesGenotype association studiesConcordanceGenotypesPhenotypeAssociation studiesFFPETTamoxifenEndoxifenWBCCYP2D6TrialsGenomic alterations in matching primary tumors and metastasis in breast cancer.
Jiang T, Szekely B, Szasz A, Kluger Y, Kulka J, Pusztai L. Genomic alterations in matching primary tumors and metastasis in breast cancer. Journal Of Clinical Oncology 2013, 31: 1549-1549. DOI: 10.1200/jco.2013.31.15_suppl.1549.Peer-Reviewed Original ResearchPrimary tumorPrimary cancerBreast cancerMetastatic lesionsDisease historyExtensive prior therapyPrimary breast cancerLonger disease historyWhole-exome sequencingDifferent tumor sitesFunctional impactPrior therapyNucleotide variantsMetastasisPatientsTumor siteTumorsCancerNormal tissuesCancer samplesExome sequencingGenomic alterationsLesionsMore mutationsExon KitCancer heterogeneity: implications for targeted therapeutics
Fisher R, Pusztai L, Swanton C. Cancer heterogeneity: implications for targeted therapeutics. British Journal Of Cancer 2013, 108: 479-485. PMID: 23299535, PMCID: PMC3593543, DOI: 10.1038/bjc.2012.581.Peer-Reviewed Original ResearchConceptsIntra-tumoural heterogeneityIntra-tumor heterogeneityClinical trial designCancer therapeuticsDistinct genomic alterationsClinical outcomesMalignant tumorsCurrent evidenceTrial designSolid tumorsSubpopulation of cellsSame tumorTumorsTissue collectionGenomic alterationsTherapeuticsBiomarker discoveryWidespread implementationEvidenceUSP-11 as a Predictive and Prognostic Factor Following Neoadjuvant Therapy in Women With Breast Cancer
Bayraktar S, Barrera A, Liu D, Pusztai L, Litton J, Valero V, Hunt K, Hortobagyi GN, Wu Y, Symmans F, Arun B. USP-11 as a Predictive and Prognostic Factor Following Neoadjuvant Therapy in Women With Breast Cancer. The Cancer Journal 2013, 19: 10-17. PMID: 23337751, PMCID: PMC3568679, DOI: 10.1097/ppo.0b013e3182801b3a.Peer-Reviewed Original ResearchConceptsNeoadjuvant systemic therapyPathological complete responseBreast cancerKaplan-Meier product-limit methodBetter survival outcomesDisease-free survivalOverall survival rateRisk of recurrenceProduct-limit methodLogistic regression modelsNeoadjuvant therapyComplete responsePrognostic factorsSystemic therapyDisease recurrencePrognostic relevanceSurvival outcomesHigh riskPatientsSurvival rateTumorsCancerRecurrencePolymerase inhibitionUbiquitin-specific protease family
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