2022
Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials
Pagani O, Walley B, Fleming G, Colleoni M, Láng I, Gomez H, Tondini C, Burstein H, Goetz M, Ciruelos E, Stearns V, Bonnefoi H, Martino S, Geyer C, Chini C, Puglisi F, Spazzapan S, Ruhstaller T, Winer E, Ruepp B, Loi S, Coates A, Gelber R, Goldhirsch A, Regan M, Francis P, Group F. Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials. Journal Of Clinical Oncology 2022, 41: 1376-1382. PMID: 36521078, PMCID: PMC10419413, DOI: 10.1200/jco.22.01064.Peer-Reviewed Original ResearchConceptsDistant recurrence-free intervalOvarian function suppressionDisease-free survivalPrimary end pointOverall survivalAdjuvant exemestaneEnd pointBreast cancerReceptor-positive early breast cancerHuman epidermal growth factor receptorClinical trial updateYears of exemestaneOverall survival benefitHigh-risk patientsPremenopausal breast cancerRecurrence-free intervalEarly breast cancerGrade 3 tumorsRisk of recurrenceEpidermal growth factor receptorGrowth factor receptorSOFT trialTreat populationOvarian suppressionPremenopausal womenAdjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT
Francis P, Fleming G, Láng I, Ciruelos E, Bonnefoi H, Bellet M, Bernardo A, Climent M, Martino S, Bermejo B, Burstein H, Davidson N, Geyer C, Walley B, Ingle J, Coleman R, Müller B, Le Du F, Loibl S, Winer E, Ruepp B, Loi S, Colleoni M, Coates A, Gelber R, Goldhirsch A, Regan M, Group F. Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT. Journal Of Clinical Oncology 2022, 41: 1370-1375. PMID: 36493334, PMCID: PMC10419521, DOI: 10.1200/jco.22.01065.Peer-Reviewed Original ResearchConceptsOvarian function suppressionDisease-free survivalAdjuvant endocrine therapyPrimary end pointOverall survivalAdjuvant tamoxifenEndocrine therapyEnd pointBreast cancerHuman epidermal growth factor receptor-2-negative tumoursTamoxifen plus ovarian function suppressionHormone receptor-positive breast cancerReceptor-positive breast cancerClinical trial updateOvarian Function TrialPremenopausal breast cancerHigher baseline riskPrior chemotherapyPremenopausal womenTrial updateClinical trialsBaseline riskMultiple end pointsTamoxifenExemestaneSurrogacy of Pathologic Complete Response in Trials of Neoadjuvant Therapy for Early Breast Cancer
Conforti F, Pala L, Bagnardi V, De Pas T, Colleoni M, Buyse M, Hortobagyi G, Gianni L, Winer E, Loibl S, Cortes J, Piccart M, Wolff AC, Viale G, Gelber RD. Surrogacy of Pathologic Complete Response in Trials of Neoadjuvant Therapy for Early Breast Cancer. JAMA Oncology 2022, 8: 1668-1675. PMID: 36201176, DOI: 10.1001/jamaoncol.2022.3755.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersBreast NeoplasmsDisease-Free SurvivalDrug ApprovalFemaleHumansNeoadjuvant TherapyConceptsSurrogate end pointsPathologic complete responseEarly breast cancerBreast cancerEnd pointComplete responseClinical outcomesClinical benefitEvent-free survival dataLong-term patient outcomesReliable surrogate end pointsTrial levelPatient clinical benefitPatients' clinical outcomesAccelerated approval processNeoadjuvant RCTNeoadjuvant therapyPatient survivalClinical trialsDrug regulatory policyEffective therapyPathological responsePatient outcomesPatient levelDrug effectsTreatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03).
Mayer EL, Fesl C, Hlauschek D, Garcia-Estevez L, Burstein HJ, Zdenkowski N, Wette V, Miller KD, Balic M, Mayer IA, Cameron D, Winer EP, Ponce Lorenzo JJ, Lake D, Pristauz-Telsnigg G, Haddad TC, Shepherd L, Iwata H, Goetz M, Cardoso F, Traina TA, Sabanathan D, Breitenstein U, Ackerl K, Metzger Filho O, Zehetner K, Solomon K, El-Abed S, Theall KP, Lu DR, Dueck A, Gnant M, DeMichele A. Treatment Exposure and Discontinuation in the PALbociclib CoLlaborative Adjuvant Study of Palbociclib With Adjuvant Endocrine Therapy for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer (PALLAS/AFT-05/ABCSG-42/BIG-14-03). Journal Of Clinical Oncology 2022, 40: 449-458. PMID: 34995105, PMCID: PMC9851679, DOI: 10.1200/jco.21.01918.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleHumansNeoplasm StagingPiperazinesProtein Kinase InhibitorsPyridinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRisk FactorsTime FactorsConceptsInvasive disease-free survivalAdjuvant endocrine therapyHuman epidermal growth factor receptorEndocrine therapyEpidermal growth factor receptorPalbociclib exposureGrowth factor receptorBreast cancerHormone Receptor-Positive/Human Epidermal Growth Factor ReceptorAddition of palbociclibNovel adjuvant treatmentDisease-free survivalEarly breast cancerFactor receptorOral cancer therapyProtocol analysisPALLAS studyAdjuvant treatmentEarly discontinuationAdjuvant studiesDiscontinuation ratesDose modificationAnalysis populationCDK4/6 inhibitorsDrug persistence
2021
Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis
Curigliano G, Mueller V, Borges V, Hamilton E, Hurvitz S, Loi S, Murthy R, Okines A, Paplomata E, Cameron D, Carey L, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Ramos J, Feng W, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Annals Of Oncology 2021, 33: 321-329. PMID: 34954044, DOI: 10.1016/j.annonc.2021.12.005.Peer-Reviewed Original ResearchConceptsProgression-free survivalMetastatic breast cancerPlacebo-combination groupOverall survivalCombination groupBreast cancerHER2CLIMB trialBrain metastasesMedian durationSafety outcomesPrimary analysisFinal overall survival analysisHuman epidermal growth factor receptor 2 positive metastatic breast cancerPositive metastatic breast cancerMeaningful survival benefitMedian overall survivalPlacebo-controlled trialOverall study populationOverall survival analysisFinal OSMetastatic HER2Placebo combinationAdverse eventsLast patientPrespecified subgroupsTrastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study
Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study. Journal Of Clinical Oncology 2021, 40: 438-448. PMID: 34890214, PMCID: PMC8824393, DOI: 10.1200/jco.21.00896.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalOverall populationTrastuzumab emtansineHigh-risk human epidermal growth factor receptorHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Early breast cancer treatmentHuman epidermal growth factor receptorAnthracycline-based chemotherapyCoprimary end pointsPrimary end pointDisease-free survivalSerious adverse eventsEarly breast cancerGlobal health statusGrowth factor receptor 2Treatment completion ratesStandard of careBreast cancer treatmentFactor receptor 2Epidermal growth factor receptorGrowth factor receptorEndocrine therapyAdverse eventsAdjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)
Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, de Aránguiz B, Haddad TC, Perelló A, Bellet M, Fohler H, Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL, groups and investigators O. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). Journal Of Clinical Oncology 2021, 40: 282-293. PMID: 34874182, PMCID: PMC10476784, DOI: 10.1200/jco.21.02554.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease ProgressionDisease-Free SurvivalFemaleHumansMastectomyMiddle AgedNeoadjuvant TherapyNeoplasm StagingPiperazinesProgression-Free SurvivalProspective StudiesProtein Kinase InhibitorsPyridinesTime FactorsConceptsHormone receptor-positive breast cancerInvasive disease-free survivalReceptor-positive breast cancerAdjuvant endocrine therapyCancer-free survivalEndocrine therapyEarly breast cancerBreast cancerAdjuvant palbociclibPALLAS trialEnd pointEarly hormone receptor-positive breast cancerBreast cancer-free survivalDistant recurrence-free survivalHuman epidermal growth factor receptorProtocol-defined analysisStandard endocrine therapyPrimary end pointSecondary end pointsAdvanced breast cancerDisease-free survivalNew safety signalsRecurrence-free survivalEvent end pointsCyclin-dependent kinase 4Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy K, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. Journal Of Clinical Oncology 2021, 39: 2375-2385. PMID: 34077270, DOI: 10.1200/jco.20.03398.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalT-DM1Breast cancerStage IStage I HER2-positive breast cancerHER2-positive breast cancerHuman epidermal growth factor receptorAdjuvant T-DM1Co-primary objectivesDisease-free survivalPatient-reported outcomesEpidermal growth factor receptorGrowth factor receptorProtocol therapyAnalysis populationTrastuzumab emtansineClinical trialsRelevant toxicityPatientsFactor receptorLess toxicityWeeksTrastuzumabCancerPaclitaxelGenomic features of rapid versus late relapse in triple negative breast cancer
Zhang Y, Asad S, Weber Z, Tallman D, Nock W, Wyse M, Bey JF, Dean KL, Adams EJ, Stockard S, Singh J, Winer EP, Lin NU, Jiang YZ, Ma D, Wang P, Shi L, Huang W, Shao ZM, Cherian M, Lustberg MB, Ramaswamy B, Sardesai S, VanDeusen J, Williams N, Wesolowski R, Obeng-Gyasi S, Sizemore GM, Sizemore ST, Verschraegen C, Stover DG. Genomic features of rapid versus late relapse in triple negative breast cancer. BMC Cancer 2021, 21: 568. PMID: 34006255, PMCID: PMC8130400, DOI: 10.1186/s12885-021-08320-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorChemotherapy, AdjuvantDatasets as TopicDisease-Free SurvivalDNA Copy Number VariationsFemaleFollow-Up StudiesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLogistic ModelsMastectomyMiddle AgedModels, GeneticMutationNeoadjuvant TherapyNeoplasm Recurrence, LocalPrognosisRisk AssessmentTime FactorsTriple Negative Breast NeoplasmsConceptsLate relapseRapid relapseImmune signaturesBreast cancerAnti-tumor CD8 T cellsBackgroundTriple-negative breast cancerTriple-negative breast cancerCD8 T cellsTumor mutation burdenIndependent validation cohortNegative breast cancerFisher's exact testPearson's chi-squared testChi-squared testLogistic regression modelsLuminal signaturePrimary TNBCTNBC subsetImmune subsetsClinical featuresValidation cohortWhole-genome copy numberPrimary tumorM1 macrophagesT cellsPalbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study
Mayer EL, Dueck AC, Martin M, Rubovszky G, Burstein HJ, Bellet-Ezquerra M, Miller KD, Zdenkowski N, Winer EP, Pfeiler G, Goetz M, Ruiz-Borrego M, Anderson D, Nowecki Z, Loibl S, Moulder S, Ring A, Fitzal F, Traina T, Chan A, Rugo HS, Lemieux J, Henao F, Lyss A, Antolin Novoa S, Wolff AC, Vetter M, Egle D, Morris PG, Mamounas EP, Gil-Gil MJ, Prat A, Fohler H, Metzger Filho O, Schwarz M, DuFrane C, Fumagalli D, Theall KP, Lu DR, Bartlett CH, Koehler M, Fesl C, DeMichele A, Gnant M. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. The Lancet Oncology 2021, 22: 212-222. PMID: 33460574, DOI: 10.1016/s1470-2045(20)30642-2.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalAdjuvant endocrine therapyDisease-free survivalInvasive disease-free survival eventsDisease-free survival eventsEndocrine therapySecond interim analysisBreast cancerInterim analysisAdverse eventsEastern Cooperative Oncology Group performance scoreSecond pre-planned interim analysisHER2-negative breast cancerEarly-stage breast cancerSurvival eventsIndependent data monitoring committeePre-planned interim analysisCommon grade 3Treatment-related deathsSerious adverse eventsProgression-free survivalEarly breast cancerMetastatic breast cancerInteractive response technologyGroup performance score
2020
A Food and Drug Administration analysis of survival outcomes comparing the Adjuvant Paclitaxel and Trastuzumab trial with an external control from historical clinical trials
Amiri-Kordestani L, Xie D, Tolaney SM, Bloomquist E, Tang S, Ibrahim A, Goldberg KB, Theoret MR, Pazdur R, Sridhara R, Winer EP, Beaver JA. A Food and Drug Administration analysis of survival outcomes comparing the Adjuvant Paclitaxel and Trastuzumab trial with an external control from historical clinical trials. Annals Of Oncology 2020, 31: 1704-1708. PMID: 32866625, DOI: 10.1016/j.annonc.2020.08.2106.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalEarly breast cancerHER2-positive early breast cancerTH armOverall survivalAdjuvant paclitaxelTrastuzumab trialsReceptor statusLow-risk early breast cancerHuman epidermal growth factor receptor 2Positive early breast cancerPropensity scoreEpidermal growth factor receptor 2De-escalate therapyDisease-free survivalGrowth factor receptor 2Progesterone receptor statusSingle-arm studyEstrogen receptor statusSingle-arm trialPatient-level dataFactor receptor 2Drug Administration analysisCovariates of ageHistorical clinical trials
2019
A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma
Mayer EL, DeMichele A, Rugo HS, Miller K, Waks AG, Come SE, Mulvey T, Jeselsohn R, Overmoyer B, Guo H, Barry WT, Bartlett C, Koehler M, Winer EP, Burstein HJ. A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma. Annals Of Oncology 2019, 30: 1514-1520. PMID: 31250880, DOI: 10.1093/annonc/mdz198.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalEstradiolFeasibility StudiesFemaleFulvestrantHumansMiddle AgedNeoplasm InvasivenessNeoplasm StagingPiperazinesProtein Kinase InhibitorsPyridinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneConceptsEarly breast cancerEndocrine therapyAdjuvant palbociclibBreast cancerHormone receptor-positive/HER2-negative metastatic breast cancerHER2-negative metastatic breast cancerPhase II feasibility studyProlong progression-free survivalRandomized phase III trialAdjuvant endocrine therapyPrimary end pointStage III diseasePhase II trialPhase III trialsProgression-free survivalMetastatic breast cancerYears of therapyStart of treatmentInvasive breast carcinomaEligible patientsFebrile neutropeniaPrior chemotherapyWeeks on/1II trialCumulative incidenceRandomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial.
Muss HB, Polley MC, Berry DA, Liu H, Cirrincione CT, Theodoulou M, Mauer AM, Kornblith AB, Partridge AH, Dressler LG, Cohen HJ, Kartcheske PA, Perez EA, Wolff AC, Gralow JR, Burstein HJ, Mahmood AA, Sutton LM, Magrinat G, Parker BA, Hart RD, Grenier D, Hurria A, Jatoi A, Norton L, Hudis CA, Winer EP, Carey L. Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial. Journal Of Clinical Oncology 2019, 37: 2338-2348. PMID: 31339827, PMCID: PMC6900836, DOI: 10.1200/jco.19.00647.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalStandard adjuvant chemotherapyEarly breast cancerAdjuvant chemotherapyAge 65 yearsStandard chemotherapyBreast cancerOlder womenBreast cancer-specific survival ratesSurvival rateHormone receptor-negative diseaseHormone receptor-negative patientsHormone receptor-positive patientsCancer-specific survival ratesPatients age 65 yearsWomen age 65 yearsReceptor-negative patientsReceptor-positive patientsOverall survival benefitPrimary end pointReceptor-negative diseaseOverall survival rateAdaptive Bayesian designNonbreast cancersRFS ratesSeven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, Schneider BP, Shen F, Fuhrman K, Baltay M, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer B, Partridge AH, Hudis CA, Krop IE, Burstein HJ, Winer EP. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer. Journal Of Clinical Oncology 2019, 37: jco.19.00066. PMID: 30939096, PMCID: PMC7587424, DOI: 10.1200/jco.19.00066.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsBreast Neoplasms, MaleChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseGenotypeHumansLymph NodesMaleMiddle AgedPaclitaxelPeripheral Nervous System DiseasesPoisson DistributionPolymorphism, Single NucleotideReceptor, ErbB-2RecurrenceRiskTrastuzumabTreatment OutcomeConceptsDisease-free survivalRecurrence-free intervalSmall HER2-positive tumorsAdjuvant paclitaxelHER2-positive tumorsLong-term outcomesTrastuzumab trialsBreast cancerOverall survivalSmall human epidermal growth factor receptor 2Breast cancer-specific survivalPaclitaxel-induced peripheral neuropathyExcellent long-term outcomesHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Human epidermal growth factor receptorPAM50 intrinsic subtypesCancer-specific survivalPhase II studyPrimary end pointGrowth factor receptor 2Positive breast cancerTreatment of patientsSeven-year followThe immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial
Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, Osmani W, Getz A, Baltay M, Dang C, Yardley D, Moy B, Marcom PK, Mittendorf EA, Krop IE, Winer EP, Tolaney SM. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Annals Of Oncology 2019, 30: 575-581. PMID: 30753274, PMCID: PMC8033534, DOI: 10.1093/annonc/mdz047.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorBreastBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMastectomyMiddle AgedPaclitaxelReceptor, ErbB-2TrastuzumabTumor BurdenTumor MicroenvironmentConceptsHER2-positive breast cancerSmall HER2-positive breast cancersImmune gene signaturesBreast cancerImmune profileAPT trialPD-L1Immune markersImmune microenvironmentSmall HER2-positive tumorsStromal PD-L1 expressionNode-negative breast cancerCell signatureGene signatureHuman epidermal growth factor receptorStromal PD-L1PD-L1 expressionHistological grade 2Luminal B tumorsB cell signaturesBreast cancer trialsHER2-positive tumorsImmune cell signaturesBasal-like tumorsHistological grade 1
2018
Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer
Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Láng I, Gómez HL, Tondini C, Ciruelos E, Burstein HJ, Bonnefoi HR, Bellet M, Martino S, Geyer CE, Goetz MP, Stearns V, Pinotti G, Puglisi F, Spazzapan S, Climent MA, Pavesi L, Ruhstaller T, Davidson NE, Coleman R, Debled M, Buchholz S, Ingle JN, Winer EP, Maibach R, Rabaglio-Poretti M, Ruepp B, Di Leo A, Coates AS, Gelber RD, Goldhirsch A, Regan MM. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. New England Journal Of Medicine 2018, 379: 122-137. PMID: 29863451, PMCID: PMC6193457, DOI: 10.1056/nejmoa1803164.Peer-Reviewed Original ResearchConceptsTamoxifen plus ovarian suppressionTamoxifen-alone groupOvarian suppressionPremenopausal womenBreast cancerAdverse eventsOverall survivalDisease-free survival ratesOvarian Function TrialYears of tamoxifenAdjuvant endocrine therapyHigher adverse eventsReceipt of chemotherapyPremenopausal breast cancerLow recurrence rateAromatase inhibitor exemestaneUse of exemestaneSuppression groupExemestane TrialDistant recurrenceEndocrine therapyRecurrence rateGrade 3ExemestaneTamoxifen
2017
Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer
X. C, Bose R, Gao F, Freedman RA, Telli ML, Kimmick G, Winer E, Naughton M, Goetz MP, Russell C, Tripathy D, Cobleigh M, Forero A, Pluard TJ, Anders C, Niravath PA, Thomas S, Anderson J, Bumb C, Banks KC, Lanman RB, Bryce R, Lalani AS, Pfeifer J, Hayes DF, Pegram M, Blackwell K, Bedard PL, Al-Kateb H, Ellis MJC. Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer. Clinical Cancer Research 2017, 23: 5687-5695. PMID: 28679771, PMCID: PMC6746403, DOI: 10.1158/1078-0432.ccr-17-0900.Peer-Reviewed Original ResearchConceptsClinical benefit rateProgression-free survivalMetastatic breast cancerStable diseaseCtDNA sequencingMedian progression-free survivalSingle-arm phase II trialCommon adverse eventsPhase II trialClinical trial participationPromising preclinical dataClin Cancer ResTumor-positive casesVariant allele frequencyProphylactic loperamideSecondary endpointsII trialPartial responseAdverse eventsTrial participationPreclinical dataBenefit rateBreast cancerWeek 4Estrogen receptorPhase 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
TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer
Jeselsohn R, Barry WT, Migliaccio I, Biagioni C, Zhao J, De Tribolet-Hardy J, Guarducci C, Bonechi M, Laing N, Winer EP, Brown M, Di Leo A, Malorni L. TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor–Positive Breast Cancer. Clinical Cancer Research 2016, 22: 5755-5764. PMID: 27185372, PMCID: PMC5124409, DOI: 10.1158/1078-0432.ccr-16-0148.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalBreast NeoplasmsDisease-Free SurvivalDouble-Blind MethodEpidermal Growth FactorEstradiolFemaleFulvestrantGene Expression ProfilingHepatocyte Nuclear Factor 3-alphaHumansMiddle AgedPostmenopauseReceptors, EstrogenSignal TransductionTranscription Factor AP-2TranscriptomeConceptsProgression-free survivalBreast cancerPredictive biomarkersCONFIRM studyMetastatic estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerGene signatureBiologic pathwaysAdvanced breast cancerMetastatic breast cancerMultivariate Cox modelPotential new therapeutic targetEstrogen receptor antagonistNew therapeutic targetsNegative predictive valuePrimary tumor samplesNovel gene signatureMetastatic ERPrimary ERReceptor antagonistFulvestrant treatmentDecreased responseCox modelER levelsPerils of the Pathologic Complete Response
Rose BS, Winer EP, Mamon HJ. Perils of the Pathologic Complete Response. Journal Of Clinical Oncology 2016, 34: 3959-3962. PMID: 27551115, DOI: 10.1200/jco.2016.68.1718.Peer-Reviewed Original Research