2021
A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer
Bellon JR, Chen YH, Rees R, Taghian AG, Wong JS, Punglia RS, Shiloh RY, Warren LEG, Krishnan MS, Phillips J, Pretz J, Jimenez R, Macausland S, Pashtan I, Andrews C, Isakoff SJ, Winer EP, Tolaney SM. A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer. International Journal Of Radiation Oncology • Biology • Physics 2021, 111: 45-52. PMID: 33713742, DOI: 10.1016/j.ijrobp.2021.03.002.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast-conserving therapyDose-limiting toxicityBCT cohortRadiation therapyConcurrent cisplatinMastectomy cohortBreast cancerEarly-stage triple-negative breast cancerThree-year disease-free survivalPhase 1 dose-escalation trialStage IILocal-regional recurrence ratePhase 2 doseAdjuvant radiation therapyDisease-free survivalDose-escalation trialPhase 1b trialDose of cisplatinHER2-positive tumorsEligible patientsUrinary infectionAdditional patientsDose escalationRecurrence rateClinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer
Keenan TE, Li T, Vallius T, Guerriero JL, Tayob N, Kochupurakkal B, Davis J, Pastorello R, Tahara RK, Anderson L, Conway J, He MX, Shannon E, Godin RE, Sorger PK, D'Andrea A, Overmoyer B, Winer EP, Mittendorf EA, Van Allen EM, Shapiro GI, Tolaney SM. Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2021, 27: 983-991. PMID: 33257427, PMCID: PMC7887044, DOI: 10.1158/1078-0432.ccr-20-3089.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerObjective response rateTriple-negative breast cancerWEE1 inhibitor adavosertibPrior linesClinical benefitBreast cancerMedian progression-free survivalTreatment-related grade 3One-sided type I errorImmune-infiltrated tumorsPhase II studyProgression-free survivalT cell infiltrationImmune gene expressionPrior chemotherapyStable diseaseProtocol therapyII studyPartial responseAdverse eventsMedian ageClinical efficacyGrade 3Tumor biopsies
2020
TBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker
Mayer EL, Abramson V, Jankowitz R, Falkson C, Marcom PK, Traina T, Carey L, Rimawi M, Specht J, Miller K, Stearns V, Tung N, Perou C, Richardson AL, Componeschi K, Trippa L, Tan-Wasielewski Z, Timms K, Krop I, Wolff AC, Winer EP. TBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker. Annals Of Oncology 2020, 31: 1518-1525. PMID: 32798689, PMCID: PMC8437015, DOI: 10.1016/j.annonc.2020.08.2064.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerHomologous recombination deficiencyPhase II studyPathologic responsePreoperative cisplatinII studyBreast cancerProspective phase II studyEffective predictive biomarkersInadequate clinical responsePreoperative chemotherapy regimenSingle-agent cisplatinHomologous recombination deficiency biomarkersGermline BRCA1/2Preoperative paclitaxelChemotherapy regimenClinical responseCisplatin chemotherapyPredictive biomarkersAlternative chemotherapyPreoperative trialInadequate responseHRD scoreStage IBaseline tissueTBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial).
Tung N, Arun B, Hacker MR, Hofstatter E, Toppmeyer DL, Isakoff SJ, Borges V, Legare RD, Isaacs C, Wolff AC, Marcom PK, Mayer EL, Lange PB, Goss AJ, Jenkins C, Krop IE, Winer EP, Schnitt SJ, Garber JE. TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial). Journal Of Clinical Oncology 2020, 38: 1539-1548. PMID: 32097092, PMCID: PMC8462533, DOI: 10.1200/jco.19.03292.Peer-Reviewed Original ResearchConceptsHER2-negative breast cancerTriple-negative breast cancerResidual cancer burden scoreBreast cancerDoxorubicin-cyclophosphamideRisk ratioStage IPathologic complete response rateHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Single-agent cisplatinComplete response ratePhase II studyPhase II trialGrowth factor receptor 2Positive breast cancerNegative breast cancerFactor receptor 2CT1-3II trialII studyNodal involvementPCR rateNegative diseasePathologic response
2015
TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer
Isakoff SJ, Mayer EL, He L, Traina TA, Carey LA, Krag KJ, Rugo HS, Liu MC, Stearns V, Come SE, Timms KM, Hartman AR, Borger DR, Finkelstein DM, Garber JE, Ryan PD, Winer EP, Goss PE, Ellisen LW. TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2015, 33: 1902-1909. PMID: 25847936, PMCID: PMC4451173, DOI: 10.1200/jco.2014.57.6660.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsBiomarkers, TumorBRCA1 ProteinBRCA2 ProteinCarboplatinCisplatinClass I Phosphatidylinositol 3-KinasesDrug Administration ScheduleFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenomic InstabilityHeterozygoteHumansLoss of HeterozygosityMiddle AgedMutationNeoplasm StagingPhosphatidylinositol 3-KinasesTreatment OutcomeTriple Negative Breast NeoplasmsConceptsMetastatic triple-negative breast cancerGermline BRCA1/2 mutationsPhase II clinical trialTriple-negative breast cancerBRCA1/2 mutationsResponse rateClinical trialsBreast cancerMulticenter phase II clinical trialEnd pointSingle-arm phase II clinical trialCoprimary end pointsExploratory end pointsObjective response ratePIK3CA mutation statusSingle-agent platinumLong-term respondersPlatinum-based chemotherapyIdentification of patientsBRCA1/2 mutation carriersGenomic instability signatureGene expression subtypesP73 gene expressionPlatinum monotherapyMutation carriers
2014
Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study
Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. The Lancet Oncology 2014, 15: 1207-1214. PMID: 25218906, PMCID: PMC4294183, DOI: 10.1016/s1470-2045(14)70391-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Ovarian EpithelialCisplatinConfidence IntervalsDisease-Free SurvivalDose-Response Relationship, DrugDrug Administration ScheduleFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMaximum Tolerated DoseMiddle AgedNeoplasm Recurrence, LocalNeoplasms, Glandular and EpithelialOvarian NeoplasmsPhthalazinesPiperazinesQuinazolinesRisk AssessmentSurvival AnalysisTreatment OutcomeConceptsProgression-free survivalRecurrent platinum-sensitive ovarian cancerPlatinum-sensitive ovarian cancerPhase 2 studyOvarian cancerOlaparib monotherapyMedian progression-free survivalGermline BRCA statusPhase 2 dosePrimary peritoneal cancerRecurrent ovarian cancerPhase 2 trialPhase 3 trialSide effect profilePhase 1 trialUS academic medical centersPatient-reported outcomesEndometrioid ovarian cancerGermline BRCA1/2 mutationsAnti-angiogenic therapyAnti-angiogenic agentsCombination of olaparibAcademic medical centerNational Cancer InstituteVEGF receptor 1Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors
Balmaña J, Tung N, Isakoff S, Graña B, Ryan P, Saura C, Lowe E, Frewer P, Winer E, Baselga J, Garber J. Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. Annals Of Oncology 2014, 25: 1656-1663. PMID: 24827126, DOI: 10.1093/annonc/mdu187.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsSolid tumorsBRCA1/2 mutationsDay 1Overall objective response rateBID days 1Grade 3 neutropeniaObjective response ratePhase I trialTreatment of patientsGermline BRCA1/2 mutationsColony-stimulating factorWarrants further investigationAdvanced breastHematologic supportMeasurable diseaseOral olaparibAdverse eventsI trialTreatment cohortsLipase elevationCisplatin dosesFrequent gradePreliminary efficacyStandard treatment
2010
Does Neoadjuvant Bevacizumab Increase Surgical Complications in Breast Surgery?
Golshan M, Garber JE, Gelman R, Tung N, Smith BL, Troyan S, Greenberg CC, Winer EP, Ryan P. Does Neoadjuvant Bevacizumab Increase Surgical Complications in Breast Surgery? Annals Of Surgical Oncology 2010, 18: 733-737. PMID: 20882415, DOI: 10.1245/s10434-010-1366-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBreast NeoplasmsChemotherapy, AdjuvantCisplatinCombined Modality TherapyFemaleHumansMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalNeoplasm StagingPostoperative ComplicationsReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSentinel Lymph Node BiopsySurvival RateTreatment OutcomeConceptsTriple-negative breast cancerSingle-arm trialNeoadjuvant cisplatinPostoperative complicationsBreast cancerTwo-sided Fisher's exact testExpander/implantsSafety of bevacizumabOperable breast cancerDefinitive local therapyBreast cancer surgeryNegative breast cancerFisher's exact testBackgroundNeoadjuvant chemotherapyNeoadjuvant settingNeoadjuvant therapyProtocol therapySurgical complicationsLocal therapyRelated complicationsCancer surgeryCisplatin therapyBreast surgeryComplicationsPatientsEfficacy 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
2009
Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer
Muss HB, Berry DA, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Becker HP, Kartcheske PA, Wheeler JD, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Magrinat G, Parker BA, Hart RD, Grenier D, Norton L, Hudis CA, Winer EP. Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer. New England Journal Of Medicine 2009, 360: 2055-2065. PMID: 19439741, PMCID: PMC3082436, DOI: 10.1056/nejmoa0810266.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCapecitabineChemotherapy, AdjuvantCisplatinCyclophosphamideDeoxycytidineDoxorubicinFemaleFluorouracilHumansKaplan-Meier EstimateMaleMethotrexateNeoplasm MetastasisNeoplasm Recurrence, LocalNeoplasm StagingReceptors, EstrogenSurvival AnalysisConceptsEarly-stage breast cancerRelapse-free survivalStandard chemotherapyBreast cancerCapecitabine groupAdjuvant chemotherapyYears of ageOlder womenIIIB breast cancerStandard chemotherapy groupPrimary end pointStandard adjuvant chemotherapyTreatment-related complicationsOverall survival rateSevere toxic effectsCapecitabine therapyEndocrine therapyHazard ratioDisease recurrenceSuch patientsLong followPositive tumorsClinical trialsChemotherapyPatients
2005
Quality of life among patients with Stage II and III breast carcinoma randomized to receive high‐dose chemotherapy with autologous bone marrow support or intermediate‐dose chemotherapy
Peppercorn J, Herndon J, Kornblith AB, Peters W, Ahles T, Vredenburgh J, Schwartz G, Shpall E, Hurd DD, Holland J, Winer E, Group T. Quality of life among patients with Stage II and III breast carcinoma randomized to receive high‐dose chemotherapy with autologous bone marrow support or intermediate‐dose chemotherapy. Cancer 2005, 104: 1580-1589. PMID: 16118805, DOI: 10.1002/cncr.21363.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntineoplastic Combined Chemotherapy ProtocolsBone Marrow TransplantationBreast NeoplasmsCarmustineChemotherapy, AdjuvantCisplatinCombined Modality TherapyCyclophosphamideDose-Response Relationship, DrugFemaleHumansMiddle AgedNeoplasm StagingQuality of LifeSurvival RateTime FactorsTransplantation, AutologousConceptsQuality of lifeFunctional Living Index-CancerPositive lymph nodesHigh-dose chemotherapySymptom Distress ScaleBreast carcinomaHDC armLymph nodesQOL scoresAutologous bone marrow supportAutologous stem cell supportMcCorkle Symptom Distress ScaleMultiple positive lymph nodesAutologous bone marrow transplantationIntensive adjuvant therapyBone marrow supportHigh-dose cyclophosphamideStem cell supportTotal QOL scoreBone marrow transplantationAdjuvant chemotherapyAdjuvant settingAdjuvant therapyMarrow supportIndex cancer
2001
New cytotoxic agents and schedules for advanced breast cancer
Burstein H, Bunnell C, Winer E. New cytotoxic agents and schedules for advanced breast cancer. Seminars In Oncology 2001, 28: 344-358. PMID: 11498829, DOI: 10.1016/s0093-7754(01)90129-0.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCisplatinClinical Trials as TopicDeoxycytidineDocetaxelDoxorubicinEnzyme InhibitorsFemaleFluorouracilGemcitabineHumansLiposomesPaclitaxelTaxoidsTopoisomerase I InhibitorsTrastuzumabVinblastineVinorelbineConceptsAdvanced breast cancerBreast cancerSide effectsUse of chemotherapyCombination of chemotherapyNovel biological agentsNew cytotoxic agentsTreatment of womenSuch biological therapiesCytotoxic chemotherapyBiological therapyVariety of agentsClinical activityAvailable agentsBetter survivalChemotherapyOral chemotherapeuticsCancerCytotoxic agentsWomenBiological agentsAgentsTherapyImportant studiesNew cytotoxic agents and schedules for advanced breast cancer
Burstein H, Bunnell C, Winer E. New cytotoxic agents and schedules for advanced breast cancer. Seminars In Oncology 2001, 28: 344-358. DOI: 10.1053/sonc.2001.26146.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCisplatinClinical Trials as TopicDeoxycytidineDocetaxelDoxorubicinEnzyme InhibitorsFemaleFluorouracilGemcitabineHumansLiposomesPaclitaxelTaxoidsTopoisomerase I InhibitorsTrastuzumabVinblastineVinorelbineConceptsAdvanced breast cancerBreast cancerSide effectsUse of chemotherapyCombination of chemotherapyNovel biological agentsNew cytotoxic agentsTreatment of womenSuch biological therapiesCytotoxic chemotherapyBiological therapyVariety of agentsClinical activityAvailable agentsBetter survivalChemotherapyOral chemotherapeuticsCancerCytotoxic agentsWomenBiological agentsAgentsTherapyImportant studies
1993
High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer.
Peters W, Ross M, Vredenburgh J, Meisenberg B, Marks L, Winer E, Kurtzberg J, Bast R, Jones R, Shpall E. High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer. Journal Of Clinical Oncology 1993, 11: 1132-43. PMID: 8501500, DOI: 10.1200/jco.1993.11.6.1132.Peer-Reviewed Original ResearchConceptsAutologous bone marrow supportPrimary breast cancerHigh-risk primary breast cancerBone marrow supportEvent-free survivalBreast cancerMarrow supportLymph nodesActuarial event-free survivalMore axillary lymph nodesHigh-dose consolidationIIIB breast cancerStandard-dose cyclophosphamideTherapy-related mortalityAdjuvant chemotherapy trialsHigh-dose cyclophosphamideAxillary lymph nodesHigh-dose chemotherapyMore lymph nodesAdjuvant chemotherapy treatmentAdjuvant therapyChemotherapy trialsStudy patientsConcurrent cancerStage IIA