2023
Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer
Tarantino P, Gupta H, Hughes M, Files J, Strauss S, Kirkner G, Feeney A, Li Y, Garrido-Castro A, Barroso-Sousa R, Bychkovsky B, DiLascio S, Sholl L, MacConaill L, Lindeman N, Johnson B, Meyerson M, Jeselsohn R, Qiu X, Li R, Long H, Winer E, Dillon D, Curigliano G, Cherniack A, Tolaney S, Lin N. Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer. Nature Communications 2023, 14: 7496. PMID: 37980405, PMCID: PMC10657399, DOI: 10.1038/s41467-023-43324-w.Peer-Reviewed Original ResearchConceptsHER2-low tumorsBreast cancerHER2-negative metastatic breast cancerMetastatic breast cancerTumor mutational burdenHigh rateComprehensive genomic characterizationHER2 0Mutational burdenBreast tumorsTumorsHER2Genomic alterationsNext-generation sequencingSignificant differencesGenomic findingsCancerGenomic landscapeMolecular underpinningsHemideletionGenomic characterizationHigher numberPatientsCopy counts
2022
p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
Ni J, Kabraji S, Xie S, Wang Y, Pan P, He X, Liu Z, Leone JP, Long HW, Brown MA, Winer EP, Dillon DAR, Lin NU, Zhao JJ. p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases. Nature Communications 2022, 13: 1473. PMID: 35304445, PMCID: PMC8933392, DOI: 10.1038/s41467-022-29081-2.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsBrain metastasesMetastatic HER2-positive breast cancerBiomarker-driven clinical trialsBreast cancer brain metastasesHER2-positive breast cancerOrthotopic patient-derived xenograftsMajority of HER2Cancer brain metastasesCDK4/6 inhibitionProtein immunohistochemistryClinical trialsBreast cancerHER2Tumor suppressor p16INK4aPatientsMetastasisBCBMAbemaciclibTucatinibXenograftsImmunohistochemistryCancerCDK4/6TrialsThe Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast CancerNeratinib and Fulvestrant in HER2-Mutated Breast Cancer
X. C, Luo J, Freedman RA, Pluard TJ, Nangia JR, Lu J, Valdez-Albini F, Cobleigh M, Jones JM, Lin NU, Winer EP, Marcom PK, Thomas S, Anderson J, Haas B, Bucheit L, Bryce R, Lalani AS, Carey LA, Goetz MP, Gao F, Kimmick G, Pegram MD, Ellis MJ, Bose R. The Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast CancerNeratinib and Fulvestrant in HER2-Mutated Breast Cancer. Clinical Cancer Research 2022, 28: 1258-1267. PMID: 35046057, DOI: 10.1158/1078-0432.ccr-21-3418.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerER cohortEstrogen receptor-positive breast cancerReceptor-positive breast cancerClinical benefit rateDual HER2 blockadePhase II trialEfficacy of neratinibHER2 blockadeNeratinib monotherapyStable diseaseII trialHER2 mutationsLobular histologyPartial responseEndocrine resistanceBenefit ratePatientsFurther evaluationCancerFulvestrantHER2NeratinibProgression
2020
Impact of tucatinib on progression free survival in patients with HER2+ metastatic breast cancer and stable or active brain metastases
Bachelot T, Lin N, Murthy R, Hurvitz S, Borges V, Oliveira M, Oakman C, Khan S, Lynch C, Westbrook K, Doyle C, Reinisch M, Colleoni M, Slamon D, Hortobagyi G, Winer E, McGoldrick S, An X, Loibl S. Impact of tucatinib on progression free survival in patients with HER2+ metastatic breast cancer and stable or active brain metastases. Annals Of Oncology 2020, 31: s359-s360. DOI: 10.1016/j.annonc.2020.08.395.Peer-Reviewed Original Research53. TUCATINIB VS PLACEBO ADDED TO TRASTUZUMAB AND CAPECITABINE FOR PATIENTS WITH PREVIOUSLY TREATED HER2+ METASTATIC BREAST CANCER (MBC) WITH BRAIN METASTASES (BM) (HER2CLIMB)
Lin N, Murthy R, Anders C, Borges V, Hurvitz S, Loi S, Abramson V, Bedard P, Oliveira M, Zelnack A, DiGiovanna M, Bachelot T, Chien A, O’Regan R, Wardley A, Mueller V, Carey L, McGoldrick S, An X, Winer E. 53. TUCATINIB VS PLACEBO ADDED TO TRASTUZUMAB AND CAPECITABINE FOR PATIENTS WITH PREVIOUSLY TREATED HER2+ METASTATIC BREAST CANCER (MBC) WITH BRAIN METASTASES (BM) (HER2CLIMB). Neuro-Oncology Advances 2020, 2: ii11-ii11. PMCID: PMC7401403, DOI: 10.1093/noajnl/vdaa073.041.Peer-Reviewed Original ResearchMetastatic breast cancerBrain metastasesCNS-PFSSecond progressionControl armEfficacy analysisBrain progressionExploratory efficacy analysesMedian CNS-PFSBaseline brain MRIMedian OSOverall deathRECIST 1.1Study therapyMedian timeInvestigator's evaluationIC diseaseLocal treatmentBreast cancerBrain MRIReduced riskCapecitabineTrastuzumabTucatinibHER2137O Tucatinib vs placebo added to trastuzumab and capecitabine in previously treated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB)
Curigliano G, Murthy R, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz S, Cameron D, Borges V, Bedard P, Oliveira M, Jakobsen E, Bachelot T, Shachar S, Mueller V, Carey L, Loibl S, Feng W, Walker L, Winer E. 137O Tucatinib vs placebo added to trastuzumab and capecitabine in previously treated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB). Annals Of Oncology 2020, 31: s62-s63. DOI: 10.1016/j.annonc.2020.03.238.Peer-Reviewed Original Research
2018
69 Chemotherapy and HER2-Directed Therapy for Metastatic Breast Cancer
Waks A, Winer E. 69 Chemotherapy and HER2-Directed Therapy for Metastatic Breast Cancer. 2018, 885-906.e8. DOI: 10.1016/b978-0-323-35955-9.00069-6.Peer-Reviewed Original ResearchMetastatic breast cancerBreast cancerHER2-positive metastatic breast cancerTriple-negative breast cancerTriple-negative diseaseBRCA-deficient breast cancersUnderstanding of treatmentDistinct disease subtypesBrain metastasesOverall survivalSystemic therapyClinical efficacyNovel therapiesDisease subtypesTherapyCancerHER2ChemotherapyImportant advancesImmunotherapyPertuzumabPatientsMetastasisSubtypesDisease
2017
T-DM1 — an important agent in the history of breast cancer management
Metzger-Filho O, Winer EP. T-DM1 — an important agent in the history of breast cancer management. Nature Reviews Clinical Oncology 2017, 14: 651-652. PMID: 28786416, DOI: 10.1038/nrclinonc.2017.123.Peer-Reviewed Original ResearchConceptsT-DM1HER2-positive breast cancerOverall survival benefitFavorable safety profileBreast cancer managementRelevant therapeutic targetTH3RESA trialProlonged followSurvival benefitSafety profileBreast cancerCancer managementTherapeutic targetLater linesImportant agentsPatientsHER2FollowCancerDiseaseTrials
2016
LBA1_PR breast cancer, locally advanced and metastatic First-line ribociclib + letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC)
Hortobagyi G, Stemmer S, Burris H, Yap Y, Sonke G, Paluch-Shimon S, Campone M, Blackwell K, André F, Winer E, Janni W, Verma S, Conte P, Arteaga C, Cameron D, Xuan F, Souami F, Miller M, Germa C, O'Shaughnessy J. LBA1_PR breast cancer, locally advanced and metastatic First-line ribociclib + letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC). Annals Of Oncology 2016, 27: vi553. DOI: 10.1093/annonc/mdw435.03.Peer-Reviewed Original ResearchOvercoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors
Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, Tuck D, Harris LN, Wong KK, Liu XS, Sicinski P, Winer EP, Krop IE, Zhao JJ. Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors. Cancer Cell 2016, 29: 255-269. PMID: 26977878, PMCID: PMC4794996, DOI: 10.1016/j.ccell.2016.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Disease Models, AnimalDrug Resistance, NeoplasmErbB ReceptorsFemaleHumansMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesNeoplasm Recurrence, LocalPhosphorylationProtein Kinase InhibitorsReceptor, ErbB-2TOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsHER2-positive breast cancerCDK4/6 inhibitorsBreast cancerEGFR/HER2Patient-derived xenograft tumorsTransgenic mouse modelInhibition of CDK4/6Tumor recurrenceXenograft tumorsMouse modelPotent suppressionTransgenic modelClinical specimensTherapeutic resistanceDual inhibitionMediate resistanceHER2CancerTSC2 phosphorylationG1 arrestCellular senescenceTherapyRb phosphorylationTumorsCDK4/6
2015
PIK3CAH1047R- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling
Cheng H, Liu P, Ohlson C, Xu E, Symonds L, Isabella A, Muller WJ, Lin NU, Krop IE, Roberts TM, Winer EP, Arteaga CL, Zhao JJ. PIK3CAH1047R- and Her2-initiated mammary tumors escape PI3K dependency by compensatory activation of MEK-ERK signaling. Oncogene 2015, 35: 2961-2970. PMID: 26640141, PMCID: PMC4896860, DOI: 10.1038/onc.2015.377.Peer-Reviewed Original ResearchConceptsBreast cancerPIK3CA mutationsMammary tumorsHER2 amplification/overexpressionHER2-positive breast cancerHER2-positive cancersPrimary mammary tumorsHER2/HER3PIK3CA-activating mutationsHER2/neuHuman breast cancerEffective treatment approachAmplification/overexpressionCompound mouse modelMEK-ERK signalingMouse mammary glandWorse prognosisCombination therapyMammary tumorigenesisMouse modelMutant PIK3CATreatment approachesHER2Combined inhibitionCompensatory activationPI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers
Wang Q, Liu P, Spangle JM, Von T, Roberts TM, Lin NU, Krop IE, Winer EP, Zhao JJ. PI3K-p110α mediates resistance to HER2-targeted therapy in HER2+, PTEN-deficient breast cancers. Oncogene 2015, 35: 3607-3612. PMID: 26500061, PMCID: PMC4846581, DOI: 10.1038/onc.2015.406.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesDrug Resistance, NeoplasmFemaleHumansLapatinibMammary Neoplasms, ExperimentalMice, KnockoutMolecular Targeted TherapyPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPTEN PhosphohydrolaseQuinazolinesReceptor, ErbB-2Signal TransductionThiazolesTumor BurdenXenograft Model Antitumor AssaysConceptsBreast tumorsP110β inhibitorsHuman epidermal growth factor receptor 2 (HER2) amplificationP110α inhibitionPTEN lossInhibition of HER2Treatment of HER2Human cancersPI3K pathway activationPTEN-deficient breast cancersGenetic mouse modelsPI3K/Akt signalingPTEN-deficient tumorsPI3K/AktDual HER2Therapeutic regimenHER2 inhibitionPIK3CA mutationsTumor regressionBreast cancerMouse modelXenograft modelHER2Null tumorsHER2 activationWhole exome sequencing (WES) in HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary responses to trastuzumab (T).
Luis I, Oh C, Wang Z, Dipiro P, Macrae E, Painter C, Kryukov G, Krop I, Winer E, Lin N, Wagle N. Whole exome sequencing (WES) in HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary responses to trastuzumab (T). Journal Of Clinical Oncology 2015, 33: 611-611. DOI: 10.1200/jco.2015.33.15_suppl.611.Peer-Reviewed Original ResearchA phase 1b trial of blood-brain barrier (BBB)-penetrant tyrosine kinase inhibitor (TKI) tesevatinib in combination with trastuzumab for patients with HER2+ metastatic breast cancer (MBC).
Jhaveri K, Hamilton E, Miller K, Roche M, Berger M, Winer E, Lin N. A phase 1b trial of blood-brain barrier (BBB)-penetrant tyrosine kinase inhibitor (TKI) tesevatinib in combination with trastuzumab for patients with HER2+ metastatic breast cancer (MBC). Journal Of Clinical Oncology 2015, 33: 608-608. DOI: 10.1200/jco.2015.33.15_suppl.608.Peer-Reviewed Original ResearchA phase 2 single-arm study to assess clinical activity, efficacy and safety of enzalutamide (ENZA) with trastuzumab in HER2+ AR+ metastatic or locally advanced breast cancer.
Trudeau M, Winer E, Steinberg J, Liosatos M, Poondru S, Dydo M, Peterson A, Gradishar W. A phase 2 single-arm study to assess clinical activity, efficacy and safety of enzalutamide (ENZA) with trastuzumab in HER2+ AR+ metastatic or locally advanced breast cancer. Journal Of Clinical Oncology 2015, 33: tps640-tps640. DOI: 10.1200/jco.2015.33.15_suppl.tps640.Peer-Reviewed Original Research
2014
Whole-exome sequencing (WES) of HER2+ metastatic breast cancer (MBC) from patients (pts) treated with prior trastuzumab (T): A correlative analysis of TBCRC003.
Wagle N, Lin N, Richardson A, Leshchiner I, Mayer I, Forero-Torres A, Hobday T, Dees E, Nanda R, Rimawi M, Guo H, Barry W, Wolff A, Gabriel S, Garraway L, Winer E, Krop I. Whole-exome sequencing (WES) of HER2+ metastatic breast cancer (MBC) from patients (pts) treated with prior trastuzumab (T): A correlative analysis of TBCRC003. Journal Of Clinical Oncology 2014, 32: 536-536. DOI: 10.1200/jco.2014.32.15_suppl.536.Peer-Reviewed Original ResearchPhase I dose-escalation trial of ONT-380 in combination with trastuzumab in participants with brain metastases from HER2+ breast cancer.
Metzger-Filho O, Barry W, Krop I, Younger W, Lawler E, Winer E, Lin N. Phase I dose-escalation trial of ONT-380 in combination with trastuzumab in participants with brain metastases from HER2+ breast cancer. Journal Of Clinical Oncology 2014, 32: tps660-tps660. DOI: 10.1200/jco.2014.32.15_suppl.tps660.Peer-Reviewed Original Research
2012
Evaluation of gene expression by RNA-seq after single dose of trastuzumab (T) reveals predictors of pathologic complete response (pCR) in HER2-positive early breast cancer.
Galanina N, Sprecher E, Bossuyt V, Sarkar S, Krop I, Winer E, Tuck D, Bruce C, Harris L. Evaluation of gene expression by RNA-seq after single dose of trastuzumab (T) reveals predictors of pathologic complete response (pCR) in HER2-positive early breast cancer. Journal Of Clinical Oncology 2012, 30: 10558-10558. DOI: 10.1200/jco.2012.30.15_suppl.10558.Peer-Reviewed Original ResearchPathologic complete responseSingle doseClinical trialsHER2-positive early breast cancerEarly breast cancer patientsEarly breast cancerBreast cancer patientsTumor core biopsiesSubsequent clinical trialsWeek time pointMost gene expression changesComplete responseCancer patientsPredictive markerCore biopsyBreast cancerImmune pathwaysTumorsTime pointsB2MGene expression changesBrief exposureHER2DoseTrials
2011
Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer
Collins LC, Marotti JD, Gelber S, Cole K, Ruddy K, Kereakoglow S, Brachtel EF, Schapira L, Come SE, Winer EP, Partridge AH. Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer. Breast Cancer Research And Treatment 2011, 131: 1061-1066. PMID: 22080245, DOI: 10.1007/s10549-011-1872-9.Peer-Reviewed Original ResearchConceptsBasal-like carcinomasBreast cancerPathologic featuresYoung womenPatient ageTumor stageMolecular phenotypesInvasive breast cancerLuminal B tumorsPoor prognostic featuresDifferent age groupsClinical characteristicsB tumorsReceptor statusPrognostic featuresCentral reviewMedical recordsTumor gradeHigh prevalenceLarge cohortGeneral populationAge groupsBiomarker expressionCancerHER2TBCRC 003: Phase II trial of trastuzumab (T) and lapatinib (L) in patients (pts) with HER2+ metastatic breast cancer (MBC).
Lin N, Mayer I, Najita J, Hobday T, Falkson C, Dees E, Rimawi M, Nanda R, Gelman R, Josephs K, Richardson A, Flores L, Van Den Abbeele A, Yap J, Arteaga C, Wolff A, Krop I, Winer E. TBCRC 003: Phase II trial of trastuzumab (T) and lapatinib (L) in patients (pts) with HER2+ metastatic breast cancer (MBC). Journal Of Clinical Oncology 2011, 29: 527-527. DOI: 10.1200/jco.2011.29.15_suppl.527.Peer-Reviewed Original Research