2023
In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.
Mutlu L, Manavella D, Bellone S, McNamara B, Harold J, Mauricio D, Siegel E, Buza N, Hui P, Hartwich T, Yang-Hartwich Y, Demirkiran C, Verzosa M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Dottino P, Schwartz P, Santin A. In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma. Molecular Cancer Therapeutics 2023, 22: 1404-1412. PMID: 37676984, DOI: 10.1158/1535-7163.mct-23-0126.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedCamptothecinCarcinomaFemaleHumansImmunoconjugatesReceptor, ErbB-2TrastuzumabUterine NeoplasmsConceptsUterine serous carcinomaAntibody-dependent cellular cytotoxicityT-DXdUSC patientsUSC cell linesTrastuzumab deruxtecanSerous carcinomaHER2 expressionClinical trialsRecurrent uterine serous carcinomaTopoisomerase I inhibitor payloadSignificant antibody-dependent cellular cytotoxicityCell linesMultiple tumor indicationsPrimary USC cell linesLow HER2 expressionFuture clinical trialsHigh recurrence ratePeripheral blood lymphocytesERBB2 gene amplificationGrowth suppressionHER2-overexpressing cell linesTumor growth suppressionOverall survivalStandard chemotherapyTrastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression
Mauricio D, Bellone S, Mutlu L, McNamara B, Manavella D, Demirkiran C, Verzosa M, Buza N, Hui P, Hartwich T, Harold J, Yang-Hartwich Y, Zipponi M, Altwerger G, Ratner E, Huang G, Clark M, Andikyan V, Azodi M, Schwartz P, Santin A. Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody–drug conjugate with topoisomerase I inhibitor payload, shows antitumor activity in uterine and ovarian carcinosarcoma with HER2/neu expression. Gynecologic Oncology 2023, 170: 38-45. PMID: 36610380, PMCID: PMC10445234, DOI: 10.1016/j.ygyno.2022.12.018.Peer-Reviewed Original ResearchConceptsHER2/neu expressionDS-8201aAntibody-drug conjugatesNeu expressionCS cell linesTrastuzumab deruxtecanOvarian carcinosarcomaTopoisomerase I inhibitor payloadCell linesAggressive gynecologic malignancyLimited therapeutic optionsEffective antibody-drug conjugatesCarcinosarcoma cell lineGynecologic malignanciesTherapeutic optionsIsotype controlSarcomatous elementsXenograft modelBystander killingFlow cytometryTumor cellsCarcinosarcomaAntitumor activityVivo studiesVivo activity
2022
The role of HER2 as a therapeutic biomarker in gynaecological malignancy: potential for use beyond uterine serous carcinoma
Talia K, Banet N, Buza N. The role of HER2 as a therapeutic biomarker in gynaecological malignancy: potential for use beyond uterine serous carcinoma. Pathology 2022, 55: 8-18. PMID: 36503635, DOI: 10.1016/j.pathol.2022.11.004.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma, MucinousBiomarkers, TumorEndometrial NeoplasmsFemaleHumansMolecular Targeted TherapyReceptor, ErbB-2ConceptsHuman epidermal growth factor receptor 2Uterine serous carcinomaRole of HER2Serous carcinomaClinical trialsHER2 overexpressionPrognostic biomarkerTherapeutic targetHigh-grade endometrioid carcinomaEpidermal growth factor receptor 2Vulvar Paget's diseaseGrowth factor receptor 2Time of diagnosisFuture clinical trialsGynaecological cancer careClinical trial dataHER2 protein overexpressionFactor receptor 2P53 mutant tumorsRecurrent diseaseSurvival benefitGynaecological malignanciesPaget's diseaseClinical benefitEndometrial carcinomaCharacteristics of HER2 Gene Amplification by Fluorescence In Situ Hybridization in Endometrial Serous Carcinoma.
Buza N, Hui P. Characteristics of HER2 Gene Amplification by Fluorescence In Situ Hybridization in Endometrial Serous Carcinoma. Archives Of Pathology & Laboratory Medicine 2022, 146: 0. PMID: 35687792, DOI: 10.5858/arpa.2021-0547-oa.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaClinical trial criteriaHER2 gene amplificationTrial criteriaHER2 immunohistochemistrySerous carcinomaAnti-human epidermal growth factor receptor 2 (HER2) therapyClinical Oncology/CollegeHER2 testing algorithmHER2 FISHProspective clinical investigationHER2 IHC 2HER2/CEP17Gene amplificationContext of breastTherapeutic responseIHC 2HER2 amplificationAverage HER2Most tumorsClinical investigationImmunohistochemistryHER2 fluorescenceTumorsMonosomy 17Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu
Yadav G, Roque DM, Bellone S, Manavella DD, Hartwich TMP, Zipponi M, Harold J, Tymon-Rosario J, Mutlu L, Altwerger G, Menderes G, Ratner E, Buza N, Hui P, Huang GS, Andikyan V, Clark M, Azodi M, Schwartz PE, Alexandrov LB, Santin AD. Synergistic activity of neratinib in combination with olaparib in uterine serous carcinoma overexpressing HER2/neu. Gynecologic Oncology 2022, 166: 351-357. PMID: 35641325, DOI: 10.1016/j.ygyno.2022.05.021.Peer-Reviewed Original ResearchConceptsUterine serous carcinomaHER2/neu expressionHER2/neuCombination of olaparibUSC xenograftsUSC cell linesNeu expressionSerous carcinomaLow HER2/neu expressionHER2/neu 3Cell linesHER2/neu gene amplificationNovel therapeutic optionsPolymerase inhibitor olaparibNeu gene amplificationDurable growth inhibitionNeratinib treatmentUSC cellsUSC patientsEndometrial cancerAggressive variantTherapeutic optionsPoor prognosisHER2/Single agent
2021
DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo
Tymon-Rosario J, Bonazzoli E, Bellone S, Manzano A, Pelligra S, Guglielmi A, Gnutti B, Nagarkatti N, Zeybek B, Manara P, Zammataro L, Harold J, Mauricio D, Buza N, Hui P, Altwerger G, Menderes G, Ratner E, Clark M, Andikyan V, Huang GS, Silasi DA, Azodi M, Schwartz PE, Santin AD. DHES0815A, a novel antibody-drug conjugate targeting HER2/neu, is highly active against uterine serous carcinomas in vitro and in vivo. Gynecologic Oncology 2021, 163: 334-341. PMID: 34452746, PMCID: PMC8722447, DOI: 10.1016/j.ygyno.2021.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedBenzodiazepinesBystander EffectCell Line, TumorCystadenocarcinoma, SerousDrug Resistance, NeoplasmFemaleHumansImmunoconjugatesMiddle AgedPrimary Cell CultureReceptor, ErbB-2TrastuzumabUterine NeoplasmsXenograft Model Antitumor AssaysConceptsHER2/neuPrimary USC cell linesUSC cell linesUterine serous carcinomaSerous carcinomaHER2/Cell linesBystander killingHER2/neu protein expressionHER2/neu overexpressionProtein expressionNovel treatment optionsAggressive histologic variantNeu protein expressionHER2 protein expressionC-erbB2 gene amplificationSignificant bystander killingUSC xenograftsEndometrial cancerNegative tumorsPoor prognosisPositive tumorsTreatment optionsPreclinical activityHistologic variantsReproducibility of scoring criteria for HER2 immunohistochemistry in endometrial serous carcinoma: a multi-institutional interobserver agreement study
Buza N, Euscher ED, Matias-Guiu X, McHenry A, Oliva E, Ordulu Z, Parra-Herran C, Rottmann D, Turner BM, Wong S, Hui P. Reproducibility of scoring criteria for HER2 immunohistochemistry in endometrial serous carcinoma: a multi-institutional interobserver agreement study. Modern Pathology 2021, 34: 1194-1202. PMID: 33536574, DOI: 10.1038/s41379-021-00746-5.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaHER2 scoring criteriaSerous carcinomaHER2 scoreGynecologic pathologistsAnti-human epidermal growth factor receptor 2 (HER2) therapyRecent successful clinical trialsInterobserver disagreementCombination of HER2Successful clinical trialsHER2 gene amplificationInterobserver agreement studyScoring criteriaInterobserver agreement ratesOverall survivalEndometrial cancerPathologic studiesHER2 statusClinical trialsGastric carcinomaHER2 testingHER2 immunohistochemistryAdvanced stageCarcinomaScoring system
2020
HER2 Testing and Reporting in Endometrial Serous Carcinoma: Practical Recommendations for HER2 Immunohistochemistry and Fluorescent In Situ Hybridization: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting
Buza N. HER2 Testing and Reporting in Endometrial Serous Carcinoma: Practical Recommendations for HER2 Immunohistochemistry and Fluorescent In Situ Hybridization: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting. International Journal Of Gynecological Pathology 2020, 40: 17-23. PMID: 33290351, DOI: 10.1097/pgp.0000000000000711.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaSerous carcinomaHER2 testingClinical trialsISGyP Companion Society SessionHER2 testing algorithmStandard chemotherapy regimenAnti-HER2 therapyRecent clinical trialsNew patient cohortCurrent clinical practiceHER2 scoring criteriaHER2 protein expressionUSCAP Annual MeetingChemotherapy regimenOverall survivalAppropriate triagingClinical benefitPatient cohortPatient enrollmentTrial criteriaTherapeutic responseTreatment approachesClinical practiceHER2 immunohistochemistryDoes Specimen Type Have an Impact on HER2 Status in Endometrial Serous Carcinoma? Discordant HER2 Status of Paired Endometrial Biopsy and Hysterectomy Specimens in the Presence of Frequent Intratumoral Heterogeneity
Rottmann D, Assem H, Matsumoto N, Wong S, Hui P, Buza N. Does Specimen Type Have an Impact on HER2 Status in Endometrial Serous Carcinoma? Discordant HER2 Status of Paired Endometrial Biopsy and Hysterectomy Specimens in the Presence of Frequent Intratumoral Heterogeneity. International Journal Of Gynecological Pathology 2020, 40: 263-271. PMID: 32897955, DOI: 10.1097/pgp.0000000000000690.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaDiscordant HER2 statusHER2 immunohistochemical scoresHER2 protein expressionSerous carcinomaHER2 statusEndometrial biopsies/curettingsImmunohistochemical scoreProtein expressionHER2 testingIntratumoral heterogeneityEndometrial biopsy/curettageProlonged progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2HER2 testing algorithmProgression-free survivalGrowth factor receptor 2HER2-negative tumorsFinal study cohortHER2-positive tumorsRecent clinical trialsSpecimen typesFactor receptor 2Optimal specimen typesHuman epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study
Erickson BK, Najjar O, Damast S, Blakaj A, Tymon-Rosario J, Shahi M, Santin A, Klein M, Dolan M, Cimino-Mathews A, Buza N, Ferriss JS, Stone RL, Khalifa M, Fader AN. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study. Gynecologic Oncology 2020, 159: 17-22. PMID: 32709539, PMCID: PMC7541557, DOI: 10.1016/j.ygyno.2020.07.016.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorChemoradiotherapy, AdjuvantCystadenocarcinoma, SerousFemaleFollow-Up StudiesHumansHysterectomyImmunohistochemistryMiddle AgedNeoplasm InvasivenessNeoplasm Recurrence, LocalNeoplasm StagingPrognosisProgression-Free SurvivalReceptor, ErbB-2Retrospective StudiesRisk AssessmentUnited StatesUterine NeoplasmsUterusConceptsHuman epidermal growth factor 2Uterine serous carcinomaHER2-positive tumorsEarly-stage diseaseOverall survivalSerous carcinomaCohort studyHER2 positivityPositive tumorsEarly stage uterine serous carcinomaLymph-vascular space invasionRecurrent uterine serous carcinomaMulti-institutional cohort studyHuman epidermal growth factor receptor 2Multi-center cohort studyEpidermal growth factor receptor 2Epidermal growth factor 2HER2-positive cohortGrowth factor receptor 2HER2-negative tumorsEquivocal IHC resultsFactor receptor 2Inferior PFSAdjuvant therapyGrowth factor 2HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand
Buza N. HER2 Testing in Endometrial Serous Carcinoma: Time for Standardized Pathology Practice to Meet the Clinical Demand. Archives Of Pathology & Laboratory Medicine 2020, 145: 687-691. PMID: 32649220, DOI: 10.5858/arpa.2020-0207-ra.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaSerous carcinomaHER2 protein expressionHER2 testingNational Comprehensive Cancer Network clinical guidelinesProlonged progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Gene amplificationStandard chemotherapy regimenProgression-free survivalProtein expressionAppropriate patient selectionGrowth factor receptor 2Recent clinical trialsSuccessful clinical outcomeHER2 protein overexpressionFactor receptor 2HER2 scoring criteriaHER2 therapyChemotherapy regimenEndometrial cancerClinical outcomesPatient selectionAggressive subtype
2019
Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy
Zammataro L, Lopez S, Bellone S, Pettinella F, Bonazzoli E, Perrone E, Zhao S, Menderes G, Altwerger G, Han C, Zeybek B, Bianchi A, Manzano A, Manara P, Cocco E, Buza N, Hui P, Wong S, Ravaggi A, Bignotti E, Romani C, Todeschini P, Zanotti L, Odicino F, Pecorelli S, Donzelli C, Ardighieri L, Angioli R, Raspagliesi F, Scambia G, Choi J, Dong W, Bilguvar K, Alexandrov LB, Silasi DA, Huang GS, Ratner E, Azodi M, Schwartz PE, Pirazzoli V, Stiegler AL, Boggon TJ, Lifton RP, Schlessinger J, Santin AD. Whole-exome sequencing of cervical carcinomas identifies activating ERBB2 and PIK3CA mutations as targets for combination therapy. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 22730-22736. PMID: 31624127, PMCID: PMC6842590, DOI: 10.1073/pnas.1911385116.Peer-Reviewed Original ResearchConceptsPI3K/AKT/mTOR pathwaySquamous cell carcinomaWhole-exome sequencingAKT/mTOR pathwayPrimary cervical cancer cell linesPIK3CA inhibitorsRecurrent cervical cancer patientsMTOR pathwayCombination of copanlisibCervical cancer patientsPI3K/Akt/mTORCervical cancer xenograftsRegression of tumorsCervical cancer cell linesCervical tumor cell linesSingle nucleotide variantsWild-type tumorsRecurrent somatic missense mutationsAkt/mTORCell linesPan-HERCancer cell linesTypes 16/18Cervical cancerCancer patientsHER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy
Rottmann D, Snir OL, Wu X, Wong S, Hui P, Santin AD, Buza N. HER2 testing of gynecologic carcinosarcomas: tumor stratification for potential targeted therapy. Modern Pathology 2019, 33: 118-127. PMID: 31477811, DOI: 10.1038/s41379-019-0358-x.Peer-Reviewed Original ResearchConceptsEndometrial serous carcinomaHER2-positive tumorsSerous carcinomaSarcoma componentHER2 statusGynecologic carcinosarcomaHER2 expression/amplificationRecent phase II clinical trialPhase II clinical trialCarboplatin-paclitaxel chemotherapyEquivocal HER2 expressionProgression-free survivalAppropriate patient selectionExpression/amplificationFemale genital tractMembranous staining patternHER2 protein expressionHER2 immunohistochemical scoresUterine primaryDismal prognosisPatient selectionCarcinoma componentMixed carcinomasHER2 expressionClinical trials
2014
HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges
Buza N, Roque DM, Santin AD. HER2/neu in Endometrial Cancer: A Promising Therapeutic Target With Diagnostic Challenges. Archives Of Pathology & Laboratory Medicine 2014, 138: 343-50. PMID: 24576030, DOI: 10.5858/arpa.2012-0416-ra.Peer-Reviewed Original ResearchConceptsEndometrial carcinomaHER2/neuPromising therapeutic targetHER2 testingClinical responseTherapeutic targetHumanized monoclonal immunoglobulin G1 antibodyMonoclonal immunoglobulin G1 antibodyUterine serous carcinomaImmunoglobulin G1 antibodyNovel therapeutic strategiesEndometrial cancerSerous adenocarcinomaSerous carcinomaCase reportDiagnostic challengeHER2 overexpressionPathogenetic featuresClinical studiesG1 antibodyTherapeutic strategiesCarcinomaTherapeutic efficacyStandardized criteriaTherapy