2020
Pembrolizumab for Early Triple-Negative Breast Cancer
Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J. Pembrolizumab for Early Triple-Negative Breast Cancer. New England Journal Of Medicine 2020, 382: 810-821. PMID: 32101663, DOI: 10.1056/nejmoa1910549.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarboplatinCyclophosphamideDoxorubicinEpirubicinFemaleHumansIntention to Treat AnalysisKaplan-Meier EstimateMiddle AgedNeoadjuvant TherapyNeoplasm StagingPaclitaxelTriple Negative Breast NeoplasmsConceptsEarly triple-negative breast cancerTriple-negative breast cancerPathological complete responseCycles of pembrolizumabPercentage of patientsDefinitive surgeryComplete responseBreast cancerNeoadjuvant chemotherapyTreatment-related adverse eventsUntreated stage IIPrimary end pointAcceptable safety profileEvent-free survivalPhase 3 trialSecond primary tumorsFirst interim analysisAdjuvant pembrolizumabTreat populationDistant recurrenceNeoadjuvant therapyPromising antitumor activityAdverse eventsSafety profilePrimary tumor
2018
Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I–III HER2-positive breast cancer
Foldi J, Mougalian S, Silber A, Lannin D, Killelea B, Chagpar A, Horowitz N, Frederick C, Rispoli L, Burrello T, Abu-Khalaf M, Sabbath K, Sanft T, Brandt DS, Hofstatter EW, Hatzis C, DiGiovanna MP, Pusztai L. Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I–III HER2-positive breast cancer. Breast Cancer Research And Treatment 2018, 169: 333-340. PMID: 29396664, DOI: 10.1007/s10549-017-4653-2.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerPhase II trialII trialNeoadjuvant chemotherapyPCR rateHormone receptorsBreast cancerGrade 3/4 adverse eventsPathologic complete response rateCyclophosphamide neoadjuvant chemotherapyComplete response rateSymptomatic heart failureAsymptomatic decreaseNeoadjuvant settingWeekly paclitaxelAdverse eventsHeart failureTherapeutic plateauCardiac functionInterim analysisStage IResponse ratePurposeThe purposePatientsNegative cases
2017
Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype
Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, Walls A, Bousamra A, Ramineni M, Sinn B, Hunt K, Buchholz TA, Valero V, Buzdar AU, Yang W, Brewster AM, Moulder S, Pusztai L, Hatzis C, Hortobagyi GN. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. Journal Of Clinical Oncology 2017, 35: jco.2015.63.101. PMID: 28135148, PMCID: PMC5455352, DOI: 10.1200/jco.2015.63.1010.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDisease-Free SurvivalDoxorubicinEpirubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualPaclitaxelPhenotypePrognosisProspective StudiesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRisk AssessmentSurvival RateTime FactorsTrastuzumabTumor BurdenConceptsResidual cancer burdenPhenotypic subsetsNeoadjuvant chemotherapyValidation cohortPrognostic riskCancer burdenRCB classBreast cancerRCB indexRelapse-free survival estimatesRelapse-free survival rateHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Hormone receptorsOriginal development cohortGrowth factor receptor 2Clinical-pathologic variablesKaplan-Meier analysisLong-term prognosisLog-rank testIndependent validation cohortBreast cancer subtypesLong-term survivalFactor receptor 2Concurrent trastuzumab
2014
Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †
Gonzalez-Angulo AM, Akcakanat A, Liu S, Green MC, Murray JL, Chen H, Palla SL, Koenig KB, Brewster AM, Valero V, Ibrahim NK, Moulder-Thompson S, Litton JK, Tarco E, Moore J, Flores P, Crawford D, Dryden MJ, Symmans WF, Sahin A, Giordano SH, Pusztai L, Do K, Mills GB, Hortobagyi GN, Meric-Bernstam F. Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †. Annals Of Oncology 2014, 25: 1122-1127. PMID: 24669015, PMCID: PMC4037860, DOI: 10.1093/annonc/mdu124.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPathological complete responseStandard neoadjuvant chemotherapyNeoadjuvant chemotherapyReverse phase protein arrayBreast cancerPrimary triple-negative breast cancerMTOR pathwayReceptor-negative breast cancerTriple receptor-negative breast cancerAddition of everolimusGrade 3 pneumonitisGrade 3/4 stomatitisPI3K/AKT/mTOR pathwayRash/desquamationClinical response rateGrade 3/4 toxicitiesPhase II studyClinical end pointsCombination of paclitaxelAKT/mTOR pathwayDirect antiproliferative activityBreast cancer cellsDownregulation of mTORII study
2012
A Systematic Evaluation of Multi-Gene Predictors for the Pathological Response of Breast Cancer Patients to Chemotherapy
Shen K, Song N, Kim Y, Tian C, Rice SD, Gabrin MJ, Symmans WF, Pusztai L, Lee JK. A Systematic Evaluation of Multi-Gene Predictors for the Pathological Response of Breast Cancer Patients to Chemotherapy. PLOS ONE 2012, 7: e49529. PMID: 23185353, PMCID: PMC3504014, DOI: 10.1371/journal.pone.0049529.Peer-Reviewed Original ResearchConceptsMulti-gene predictorsPatients' clinical outcomesClinical outcomesCancer patientsTherapeutic responseStandard combination chemotherapyBreast cancer patientsClinical outcome measurementsPatient's therapeutic responseBreast cancer cell linesCancer cell linesNegative patientsCombination chemotherapyPatient cohortPathological responseBreast cancerEstrogen receptorClinical utilityOutcome measurementsChemotherapyPatientsCell linesOutcomesPredictorsCOXEN
2011
Multifactorial Approach to Predicting Resistance to Anthracyclines
Desmedt C, Di Leo A, de Azambuja E, Larsimont D, Haibe-Kains B, 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. Multifactorial Approach to Predicting Resistance to Anthracyclines. Journal Of Clinical Oncology 2011, 29: 1578-1586. PMID: 21422418, DOI: 10.1200/jco.2010.31.2231.Peer-Reviewed Original ResearchMeSH KeywordsAntibiotics, AntineoplasticAntigens, NeoplasmBiomarkers, TumorBiopsyBreast NeoplasmsChemotherapy, AdjuvantDNA Topoisomerases, Type IIDNA-Binding ProteinsDrug Resistance, NeoplasmEpirubicinEuropeFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedNeoadjuvant TherapyOdds RatioPatient SelectionPoly-ADP-Ribose Binding ProteinsPredictive Value of TestsProspective StudiesReceptor, ErbB-2Receptors, EstrogenReproducibility of ResultsRisk AssessmentRisk FactorsTexasTreatment FailureConceptsPathologic complete responseHuman epidermal growth factor receptor 2Neoadjuvant trialsTOP trialPredictive valueEstrogen receptor-negative tumorsEpidermal growth factor receptor 2High negative predictive valuePrimary end pointGrowth factor receptor 2Receptor-negative tumorsResponse/resistanceFactor receptor 2Negative predictive valueUseful clinical toolER-negative samplesA scoresAnthracycline monotherapyEvaluable patientsGene expression signaturesComplete responseBreast cancerImmune responseReceptor 2Patients
2010
Cyclophosphamide Dose Intensification May Circumvent Anthracycline Resistance of p53 Mutant Breast Cancers
Lehmann‐Che J, André F, Desmedt C, Mazouni C, Giacchetti S, Turpin E, Espié M, Plassa L, Marty M, Bertheau P, Sotiriou C, Piccart M, Symmans WF, Pusztai L, de Thé H. Cyclophosphamide Dose Intensification May Circumvent Anthracycline Resistance of p53 Mutant Breast Cancers. The Oncologist 2010, 15: 246-252. PMID: 20228131, PMCID: PMC3227956, DOI: 10.1634/theoncologist.2009-0243.Peer-Reviewed Original ResearchConceptsPathologic complete responseBreast cancer patientsCancer patientsDose intensificationDose intensityP53 statusAnthracycline resistanceHigh-dose cyclophosphamide administrationP53-mutant breast cancersAnthracycline-based regimensTriple-negative tumorsPretreatment tumor samplesMutant breast cancerChemotherapy regimensComplete responseER expressionCyclophosphamide administrationER- tumorsTumor responsePooled resultsBreast cancerYeast functional assayPatientsPredictive valueMultivariate analysis
2008
Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab
Peintinger F, Buzdar AU, Kuerer HM, Mejia JA, Hatzis C, Gonzalez-Angulo AM, Pusztai L, Esteva FJ, Dawood SS, Green MC, Hortobagyi GN, Symmans WF. Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. Annals Of Oncology 2008, 19: 2020-2025. PMID: 18667396, PMCID: PMC2733116, DOI: 10.1093/annonc/mdn427.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials as TopicCyclophosphamideDoxorubicinEpirubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualNeoplasms, Hormone-DependentPaclitaxelRandomized Controlled Trials as TopicReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTrastuzumabConceptsHER2-positive breast cancerHormone receptor statusPathologic complete responseResidual cancer burdenPathologic responseBreast cancerNeoadjuvant chemotherapyReceptor statusExtensive residual diseaseHR-negative cancerHR-positive cancersPathologic response rateAddition of trastuzumabNeo-adjuvant chemotherapyStandard neoadjuvant chemotherapyFEC chemotherapyHR-/HER2Pathologic reviewComplete responseLymph nodesCancer burdenResidual diseasePrimary tumorChemotherapyResponse rate
2007
CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer
Esteva FJ, Wang J, Lin F, Mejia JA, Yan K, Altundag K, Valero V, Buzdar AU, Hortobagyi GN, Symmans WF, Pusztai L. CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer. Breast Cancer Research 2007, 9: r87. PMID: 18086299, PMCID: PMC2246190, DOI: 10.1186/bcr1836.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBiopsy, Fine-NeedleBreast NeoplasmsCD40 AntigensCyclophosphamideEpirubicinFemaleFluorouracilGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMastectomyMastectomy, Modified RadicalMastectomy, SegmentalMiddle AgedNeoadjuvant TherapyNeoplasm StagingNeoplasm, ResidualPaclitaxelPredictive Value of TestsReceptor, ErbB-2RNA, MessengerSignal TransductionTranscription, GeneticTrastuzumabTreatment OutcomeUp-RegulationConceptsPathologic complete responseBreast cancerIIIA breast cancerFine-needle aspirationConcomitant paclitaxelConcomitant trastuzumabFEC therapyPreoperative trastuzumabPreoperative chemotherapyPrimary endpointComplete responseNodal statusResidual cancerTumor sizeTumor responseNuclear gradeReceptor mRNAMolecular predictorsTrastuzumabStage IIGreater riskLow expressionCancerCyclophosphamidePatientsNeoadjuvant Therapy with Paclitaxel followed by 5-Fluorouracil, Epirubicin, and Cyclophosphamide Chemotherapy and Concurrent Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer: An Update of the Initial Randomized Study Population and Data of Additional Patients Treated with the Same Regimen
Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant Therapy with Paclitaxel followed by 5-Fluorouracil, Epirubicin, and Cyclophosphamide Chemotherapy and Concurrent Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer: An Update of the Initial Randomized Study Population and Data of Additional Patients Treated with the Same Regimen. Clinical Cancer Research 2007, 13: 228-233. PMID: 17200359, DOI: 10.1158/1078-0432.ccr-06-1345.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptorPathologic CR rateEpidermal growth factor receptorConcurrent trastuzumabGrowth factor receptorCR rateEfficacy dataBreast cancerStudy populationHigher pathologic complete remission rateSecond cohortPathologic complete remission rateCardiac safety dataCycles of FECCycles of paclitaxelOperable breast cancerComplete remission rateDisease-free survivalFactor receptorBreast cancer patientsNew safety concernsSame chemotherapyWeekly trastuzumabCyclophosphamide chemotherapyNeoadjuvant therapy
2006
Kinetics of serum HER‐2/neu changes in patients with HER‐2‐positive primary breast cancer after initiation of primary chemotherapy
Mazouni C, Hall A, Broglio K, Fritsche H, Andre F, Esteva FJ, Hortobagyi GN, Buzdar AU, Pusztai L, Cristofanilli M. Kinetics of serum HER‐2/neu changes in patients with HER‐2‐positive primary breast cancer after initiation of primary chemotherapy. Cancer 2006, 109: 496-501. PMID: 17149760, DOI: 10.1002/cncr.22418.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularCyclophosphamideEpirubicinFemaleFluorouracilHumansKineticsMiddle AgedNeoadjuvant TherapyPrognosisProspective StudiesReceptor, ErbB-2TrastuzumabConceptsPrimary breast cancerPathological complete responseBreast cancerECD levelsPrimary chemotherapyNeoadjuvant therapyPathological responseWeek 6HER-2 extracellular domainWeek 3HER-2/neu receptorCycles of fluorouracilCycles of paclitaxelNeu extracellular domainTrastuzumab-based regimensUtility of quantitationInitiation of chemotherapyExtracellular domainSame chemotherapyWeekly trastuzumabInitial chemotherapyNeoadjuvant chemotherapyComplete responseTreatment regimenResidual disease
2005
Microtubule-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 testsPaclitaxelCancerChemotherapySignificantly Higher Pathologic Complete Remission Rate After Neoadjuvant Therapy With Trastuzumab, Paclitaxel, and Epirubicin Chemotherapy: Results of a Randomized Trial in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer
Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, Pusztai L, Green MC, Arun BK, Giordano SH, Cristofanilli M, Frye DK, Smith TL, Hunt KK, Singletary SE, Sahin AA, Ewer MS, Buchholz TA, Berry D, Hortobagyi GN. Significantly Higher Pathologic Complete Remission Rate After Neoadjuvant Therapy With Trastuzumab, Paclitaxel, and Epirubicin Chemotherapy: Results of a Randomized Trial in Human Epidermal Growth Factor Receptor 2–Positive Operable Breast Cancer. Journal Of Clinical Oncology 2005, 23: 3676-3685. PMID: 15738535, DOI: 10.1200/jco.2005.07.032.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCyclophosphamideDisease-Free SurvivalEpirubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyPaclitaxelProspective StudiesReceptor, ErbB-2Remission InductionTrastuzumabConceptsClinical congestive heart failureHuman epidermal growth factor receptorOperable breast cancerAddition of trastuzumabCongestive heart failureChemotherapy armData monitoring committeeEpidermal growth factor receptorGrowth factor receptorHeart failureBreast cancerHigher pathologic complete remission ratePathologic complete remission ratePathologic complete response rateCycles of fluorouracilCycles of paclitaxelHER2-positive diseaseComplete response rateComplete remission rateFactor receptorCardiac ejection fractionNeoadjuvant settingSame chemotherapyWeekly trastuzumabNeoadjuvant therapy