2022
Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases
Kabraji S, Ni J, Sammons S, Li T, Van Swearingen AED, Wang Y, Pereslete A, Hsu L, DiPiro PJ, Lascola C, Moore H, Hughes M, Raghavendra AS, Gule-Monroe M, Murthy RK, Winer EP, Anders CK, Zhao JJ, Lin NU. Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases. Clinical Cancer Research 2022, 29: 174-182. PMID: 36074155, PMCID: PMC9811155, DOI: 10.1158/1078-0432.ccr-22-1138.Peer-Reviewed Original ResearchConceptsBreast cancer brain metastasesActive brain metastasesObjective response rateCNS objective response rateCancer brain metastasesBrain metastasesT-DXdPatient-derived xenograftsPDX modelsCohort studyTrastuzumab deruxtecanClinical efficacyClinical trialsHER2-positive breast cancer brain metastasesMetastatic HER2-positive breast cancerResponse rateMulti-institutional cohort studyHER2-positive breast cancerRetrospective multi-institutional cohort studyOrthotopic patient-derived xenograftsRetrospective cohort studyProspective clinical trialsSubset of patientsCentral nervous system activityPivotal clinical trials
2021
Impact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab
Filho OM, Viale G, Stein S, Trippa L, Yardley DA, Mayer IA, Abramson VG, Arteaga CL, Spring LM, Waks AG, Wrabel E, DeMeo MK, Bardia A, Dell'Orto P, Russo L, King TA, Polyak K, Michor F, Winer EP, Krop IE. Impact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab. Cancer Discovery 2021, 11: candisc.1557.2020. PMID: 33941592, PMCID: PMC8598376, DOI: 10.1158/2159-8290.cd-20-1557.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerHER2 heterogeneityBreast cancerEarly-stage HER2-positive breast cancerHER2-positive early-stage breast cancerTherapeutic resistancePathologic complete response rateEarly-stage breast cancerNeoadjuvant clinical trialsComplete response rateSubset of patientsHER2 therapyPretreatment biopsiesEvaluable casesCure rateT-DM1Trastuzumab emtansineClinical trialsTreatment strategiesTreatment responseTreatment selectionResponse rateRelated commentaryTherapyIssue feature
2020
Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavilá J, Serra V, Prat A, Paré L, Céliz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Research 2020, 22: 120. PMID: 33138866, PMCID: PMC7607628, DOI: 10.1186/s13058-020-01354-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClass I Phosphatidylinositol 3-KinasesDisease ProgressionFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedMorpholinesNeoplasm MetastasisPatient SafetyProtein Kinase InhibitorsProteomicsResponse Evaluation Criteria in Solid TumorsSurvival RateTreatment OutcomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerProgression-free survivalPan-class I PI3K inhibitorMetastatic triple-negative breast cancerStable diseasePhase 2 studyBreast cancerOverall survivalPI3K inhibitorsPI3K pathwayPartial responseComplete responseClinical benefitSingle-arm phase 2 studyTriple-negative metastatic breast cancerMedian progression-free survivalK inhibitorsClinical benefit rateEfficacy of buparlisibK pathwayFrequent adverse eventsMedian overall survivalPercent of patientsMetastatic breast cancerSubset of patientsPrevalence and mutational determinants of high tumor mutation burden in breast cancer
Barroso-Sousa R, Jain E, Cohen O, Kim D, Buendia-Buendia J, Winer E, Lin N, Tolaney S, Wagle N. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Annals Of Oncology 2020, 31: 387-394. PMID: 32067680, DOI: 10.1016/j.annonc.2019.11.010.Peer-Reviewed Original ResearchConceptsHigh tumor mutation burdenTumor mutation burdenPD-1 inhibitorsBreast cancerMutation burdenMedian tumor mutation burdenDifferent mutational signaturesPembrolizumab-based therapyMetastatic breast cancerSubset of patientsMut/MbMismatch repair deficiencyGenomic profilesMutational patternsAPOBEC activityGene panel sequencingMultiple tumor typesWhole-exome sequencingDe-identified dataDurable responsesMetastatic tumorsPrimary tumorTumor subtypesPatientsTumor types
2019
PIK3CA and MAP3K1 alterations imply luminal A status and are associated with clinical benefit from pan-PI3K inhibitor buparlisib and letrozole in ER+ metastatic breast cancer
Nixon MJ, Formisano L, Mayer IA, Estrada MV, González-Ericsson PI, Isakoff SJ, Forero-Torres A, Won H, Sanders ME, Solit DB, Berger MF, Cantley LC, Winer EP, Arteaga CL, Balko JM. PIK3CA and MAP3K1 alterations imply luminal A status and are associated with clinical benefit from pan-PI3K inhibitor buparlisib and letrozole in ER+ metastatic breast cancer. Npj Breast Cancer 2019, 5: 31. PMID: 31552290, PMCID: PMC6757060, DOI: 10.1038/s41523-019-0126-6.Peer-Reviewed Original ResearchMetastatic breast cancerClinical benefitBreast cancerPan-PI3K inhibitor buparlisibHuman epidermal growth factor 2Epidermal growth factor 2K inhibitorsPan-PI3K inhibitorPhase Ib studySubset of patientsPI3KBreast cancer cell linesPI3K inhibitorsPAM50 analysisCancer cell linesEndocrine therapyGrowth factor 2Only biomarkerPIK3CA mutationsClinical trialsMetastatic tissuesTherapeutic combinationsIb studyPatientsBuparlisibCharacterization of mutational processes in ER+ metastatic breast cancer.
Buendia-Buendia J, Cohen O, Kim D, Jain E, Winer E, Lin N, Wagle N. Characterization of mutational processes in ER+ metastatic breast cancer. Journal Of Clinical Oncology 2019, 37: 1019-1019. DOI: 10.1200/jco.2019.37.15_suppl.1019.Peer-Reviewed Original ResearchMetastatic breast cancerEarly-stage breast cancerSubset of patientsStage breast cancerWhole-exome sequencingBreast cancerManagement of MBCMutational signaturesMBC samplesMetastatic tumor biopsiesNormal aging processEndocrine therapyMetastatic settingCancer Genome AtlasClinical featuresClinical trialsDisease progressionTumor biopsiesPrimary biopsiesMutational burdenTumor evolutionBreast tumorsMBC tumorsCancerTumor samplesPembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study
Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, Hui R, Curigliano G, Toppmeyer D, O’Shaughnessy J, Loi S, Paluch-Shimon S, Tan AR, Card D, Zhao J, Karantza V, Cortés J. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study. Annals Of Oncology 2019, 30: 397-404. PMID: 30475950, DOI: 10.1093/annonc/mdy517.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerDisease control ratePD-L1Positive populationPembrolizumab monotherapyMetastatic diseaseControl rateBreast cancerTreatment-related adverse eventsEnd pointManageable safety profileObjective response ratePrimary end pointSecondary end pointsProgression-free survivalSubset of patientsDurable antitumor activityDuration of responseLine of treatmentEligible patientsMedian OSMedian PFSAdverse eventsMedian duration
2018
Enzalutamide for the Treatment of Androgen Receptor–Expressing Triple-Negative Breast Cancer
Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O'Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, Nanda R, Gucalp A, Awada A, Garcia-Estevez L, Trudeau ME, Steinberg J, Uppal H, Tudor IC, Peterson A, Cortes J. Enzalutamide for the Treatment of Androgen Receptor–Expressing Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2018, 36: jco.2016.71.349. PMID: 29373071, PMCID: PMC5858523, DOI: 10.1200/jco.2016.71.3495.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerClinical benefit rateAR-positive triple-negative breast cancerProgression-free survivalAndrogen receptorNuclear androgen receptorEvaluable subgroupITT populationBreast cancerEnd pointAdverse eventsAdvanced triple-negative breast cancerMedian progression-free survivalTreatment-related grade 3Safety of enzalutamideHigher adverse eventsMedian overall survivalPhase II studyPrimary end pointSecondary end pointsSubset of patientsII studyOverall survivalPostbaseline assessmentSafety profile
2017
Phase II and Biomarker Study of Cabozantinib in Metastatic Triple‐Negative Breast Cancer Patients
Tolaney SM, Ziehr DR, Guo H, Ng MR, Barry WT, Higgins MJ, Isakoff SJ, Brock JE, Ivanova EV, Paweletz CP, Demeo MK, Ramaiya NH, Overmoyer BA, Jain RK, Winer EP, Duda DG. Phase II and Biomarker Study of Cabozantinib in Metastatic Triple‐Negative Breast Cancer Patients. The Oncologist 2017, 22: 25-32. PMID: 27789775, PMCID: PMC5313267, DOI: 10.1634/theoncologist.2016-0229.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnilidesBiomarkers, TumorDisease-Free SurvivalFemaleHumansKaplan-Meier EstimateMiddle AgedMolecular Targeted TherapyNeoplasm MetastasisPlacenta Growth FactorProtein Kinase InhibitorsProto-Oncogene Proteins c-metPyridinesTriple Negative Breast NeoplasmsVascular Endothelial Growth Factor DVascular Endothelial Growth Factor Receptor-2ConceptsProgression-free survivalVascular endothelial growth factorBreast cancer patientsStable diseasePrimary endpointPartial responseCancer patientsBreast cancerMetastatic triple-negative breast cancer patientsMedian progression-free survivalSingle-arm phase IILonger progression-free survivalTriple-negative breast cancer patientsSoluble VEGF receptor 2Plasma placental growth factorTriple-negative breast cancerBiomarker studiesGrowth factorClinical benefit rateCytotoxic lymphocyte populationsGrade 4 toxicityObjective response ratePalmar-plantar erythrodysesthesiaSubset of patientsStromal cell-derived factor 1a
2016
Impact of neoadjuvant therapy on eligibility for and frequency of breast conservation in stage II–III HER2-positive breast cancer: surgical results of CALGB 40601 (Alliance)
Golshan M, Cirrincione CT, Sikov WM, Carey LA, Berry DA, Overmoyer B, Henry NL, Somlo G, Port E, Burstein HJ, Hudis C, Winer E, Ollila DW, for the Alliance for Clinical Trials in Oncology. Impact of neoadjuvant therapy on eligibility for and frequency of breast conservation in stage II–III HER2-positive breast cancer: surgical results of CALGB 40601 (Alliance). Breast Cancer Research And Treatment 2016, 160: 297-304. PMID: 27704226, PMCID: PMC5189982, DOI: 10.1007/s10549-016-4006-6.Peer-Reviewed Original ResearchConceptsNeoadjuvant systemic therapyBreast-conserving therapyBCT-eligible patientsPathologic complete responseSuccessful breast-conserving therapyHER2-positive breast cancerBCT eligibilityPCR rateBreast conservationSurgical assessmentBreast cancerStage IIHigh clinical response rateFinal surgical procedureClinical response rateSubset of patientsManagement of patientsPoor cosmetic outcomeSuccess rateCALGB 40601Converted patientsNeoadjuvant trialsNeoadjuvant therapyPrimary surgeryMulticentric diseaseAdjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression
Burstein HJ, Lacchetti C, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, Giordano SH, Hudis CA, Solky AJ, Stearns V, Winer EP, Griggs JJ. Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. Journal Of Clinical Oncology 2016, 34: 1689-1701. PMID: 26884586, DOI: 10.1200/jco.2015.65.9573.Peer-Reviewed Original ResearchConceptsReceptor-positive breast cancerAdjuvant endocrine therapyOvarian suppressionStandard adjuvant therapyEndocrine therapyBreast cancerAdjuvant chemotherapyAdjuvant therapyAromatase inhibitorsClinical Oncology Clinical Practice Guideline UpdateHormone receptor-positive breast cancerEstrogen receptor-positive breast cancerClinical Practice Guideline UpdateStage I breast cancerDisease-free survivalHigh-risk patientsLow-risk patientsI breast cancerSubset of patientsOverall clinical benefitRandomized clinical trialsNode-negative cancersQuality of lifeDistant recurrencePremenopausal women
2014
NI-23BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION
Emblem K, Pinho M, Chandra V, Gerstner E, Stufflebeam S, Sorenson G, Harris G, Freedman R, Sohl J, Younger J, Krop I, Winer E, Lin N. NI-23BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION. Neuro-Oncology 2014, 16: v143-v143. PMCID: PMC4218348, DOI: 10.1093/neuonc/nou264.22.Peer-Reviewed Original ResearchAnti-angiogenic therapyBreast cancerBrain metastasesVascular normalizationTumor perfusionBrain tumorsDay 1Largest contrast-enhancing lesionPerfusion MRIParenchymal brain metastasesMonths of therapyPhase II studyHormone receptor statusMetastatic breast cancerSubset of patientsContrast-enhancing lesionsPrimary brain tumorsAnti-angiogenic effectsOxygen saturation levelsPrior therapyBreast metastasisII studySystemic therapyImproved survivalReceptor status
2013
PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer
Martín M, Prat A, Rodríguez-Lescure Á, Caballero R, Ebbert MT, Munárriz B, Ruiz-Borrego M, Bastien RR, Crespo C, Davis C, Rodríguez CA, López-Vega JM, Furió V, García AM, Casas M, Ellis MJ, Berry DA, Pitcher BN, Harris L, Ruiz A, Winer E, Hudis C, Stijleman IJ, Tuck DP, Carrasco E, Perou CM, Bernard PS. PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer. Breast Cancer Research And Treatment 2013, 138: 457-466. PMID: 23423445, PMCID: PMC3608881, DOI: 10.1007/s10549-013-2416-2.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCell ProliferationClinical Trials, Phase III as TopicCyclophosphamideEpirubicinFemaleFluorouracilHumansKaplan-Meier EstimateKi-67 AntigenMiddle AgedMulticenter Studies as TopicMultivariate AnalysisPaclitaxelProportional Hazards ModelsProspective StudiesRandomized Controlled Trials as TopicTreatment OutcomeConceptsGroup of patientsWeekly paclitaxelOverall survivalPAM50 subtypesProliferation scoreBreast cancerNode-positive operable breast cancerMultivariable Cox regression analysisLow proliferation statusAnthracycline-containing chemotherapyOperable breast cancerPhase III trialsSubset of patientsCox regression analysisClinical-pathological variablesFEC armMedian followAdjuvant therapySecondary endpointsIII trialsPathological variablesHistologic gradeClinical trialsAdjuvant FECKi-67
2011
Adjuvant chemotherapy in luminal breast cancers
Lim E, Winer EP. Adjuvant chemotherapy in luminal breast cancers. The Breast 2011, 20: s128-s131. PMID: 22015279, DOI: 10.1016/s0960-9776(11)70309-5.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Agents, HormonalBiomarkersBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleHumansMiddle AgedNeoplasm StagingNeoplasms, Hormone-DependentPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRisk AssessmentSurvival AnalysisTreatment OutcomeConceptsAdjuvant endocrine therapyLuminal breast cancerEndocrine therapyBreast cancerEstrogen receptorAdjuvant chemotherapyProgesterone receptorHER2-negative breast cancerER-positive breast tumorsAddition of chemotherapyER-positive diseaseER-positive tumorsUse of chemotherapySubset of patientsSubgroup of patientsER-negative tumorsAdditional therapyCytotoxic chemotherapyEndocrine sensitivityClinicians' estimationTherapeutic responseFavorable outcomeCurrent biomarkersChemotherapyBreast tumors
2010
International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured?
Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, Costa A, Winer EP, Cardoso F. International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured? Journal Of The National Cancer Institute 2010, 102: 456-463. PMID: 20220104, PMCID: PMC3298957, DOI: 10.1093/jnci/djq029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Combined Chemotherapy ProtocolsBone NeoplasmsBreast NeoplasmsCatheter AblationChemotherapy, AdjuvantClinical Trials as TopicCongresses as TopicConsensus Development Conferences as TopicDose-Response Relationship, DrugEarly Detection of CancerEuropeFemaleGene Expression ProfilingHumansImmunosuppressive AgentsInterdisciplinary CommunicationInternational CooperationLiver NeoplasmsLung NeoplasmsNeoplasm StagingNeoplastic Cells, CirculatingObserver VariationPatient Care TeamPatient SelectionPractice Guidelines as TopicRadiotherapy, AdjuvantSurvival RateConceptsMetastatic breast cancerOligometastatic diseaseBreast cancerMetastatic lesionsPrimary tumorEuropean Breast Cancer ConferenceFirst consensus recommendationsOptimal local treatmentRapid disease controlAvailable therapeutic optionsSubset of patientsLong-term outcomesLarge retrospective seriesDetectable metastatic lesionsAttractive therapeutic strategyChemotherapy optionsSurvival benefitSystemic therapyTreatment guidelinesRegional chemotherapyRetrospective seriesTask ForceLung metastasesTherapeutic optionsPatient populationEfficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer
Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, Fatima A, Gelman RS, Ryan PD, Tung NM, De Nicolo A, Ganesan S, Miron A, Colin C, Sgroi DC, Ellisen LW, Winer EP, Garber JE. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2010, 28: 1145-1153. PMID: 20100965, PMCID: PMC2834466, DOI: 10.1200/jco.2009.22.4725.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBreast NeoplasmsCisplatinDNA MethylationDNA-Binding ProteinsFemaleGenes, BRCA1Genes, p53HumansMiddle AgedMutationNeoadjuvant TherapyNuclear ProteinsOligonucleotide Array Sequence AnalysisPromoter Regions, GeneticReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTumor Protein p73Tumor Suppressor ProteinsConceptsTriple-negative breast cancerBreast cancerSubset of TNBCCisplatin responseSporadic triple-negative breast cancerGood pathologic responsePathologic treatment responseSingle-agent cisplatinCycles of cisplatinStandard adjuvant chemotherapyPathologic complete responseSubset of patientsPredictors of responseBasal-like tumorsPretreatment tumor samplesBreast cancer treatmentHER2/neuBRCA1 promoter methylationBRCA1 mRNA expressionAdjuvant chemotherapyNeoadjuvant cisplatinNeoadjuvant trialsDefinitive surgeryGene expression signaturesPartial response