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 ResearchConceptsUterine 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 chemotherapy
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 ResearchConceptsHuman 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 carcinomaSynergistic 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
Minimal uterine serous carcinoma and endometrial polyp: a close clinicopathological relationship
Assem H, Rottmann D, Finkelstein A, Wang M, Ratner E, Santin AD, Buza N, Hui P. Minimal uterine serous carcinoma and endometrial polyp: a close clinicopathological relationship. Human Pathology 2021, 118: 1-8. PMID: 34508766, DOI: 10.1016/j.humpath.2021.09.001.Peer-Reviewed Original ResearchConceptsMinimal uterine serous carcinomaEndometrial polypsUterine serous carcinomaSerous carcinomaHigh stage patientsLow stage patientsPelvic washing cytologyAdvanced stage diseaseEndometrial serous carcinomaHigher stage diseaseLower tumor stageClinical outcome assessmentClose topographic relationshipBackground endometriumExtrauterine diseaseExtrauterine spreadStage diseaseExcellent prognosisLymphovascular invasionClinicopathological relationshipWashing cytologyTumor stageHigh riskPatientsLarge seriesDHES0815A, 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 variants
2020
Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort
Najjar O, Erickson B, Klein M, Dolan M, Shahi M, Grandelis A, Buza N, Tymon-Rosario J, Santin A, Ferriss J, Fader A. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort. Gynecologic Oncology 2020, 159: e13. DOI: 10.1016/j.ygyno.2020.07.048.Peer-Reviewed Original ResearchRandomized phase II trial of carboplatin-paclitaxel compared to carboplatin-paclitaxel-trastuzumab in advanced or recurrent uterine serous carcinomas that overexpress HER2/Neu (NCT01367002): Updated survival analysis
Fader A, Roque D, Siegel E, Buza N, Hui P, Havrilesky L, Secord A, O'Malley D, Backes F, Nevadunsky N, Chambers S, Edraki B, Celano P, Bellone S, Azodi M, Ratner E, Litkouhi B, Silasi D, Schwartz P, Santin A. Randomized phase II trial of carboplatin-paclitaxel compared to carboplatin-paclitaxel-trastuzumab in advanced or recurrent uterine serous carcinomas that overexpress HER2/Neu (NCT01367002): Updated survival analysis. Gynecologic Oncology 2020, 159: 7-8. DOI: 10.1016/j.ygyno.2020.06.014.Peer-Reviewed Original ResearchHuman 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 2Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort.
Erickson B, Najjar O, Klein M, Shahi M, Dolan M, Cimino-Mathews A, Grandelis A, Buza N, Delaney P, Tymon-Rosario J, Santin A, Ferriss J, Stone R, Nickles Fader A. Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort. Journal Of Clinical Oncology 2020, 38: 6084-6084. DOI: 10.1200/jco.2020.38.15_suppl.6084.Peer-Reviewed Original ResearchHuman epidermal growth factor 2Uterine serous carcinomaEarly stage uterine serous carcinomaEarly-stage diseaseMulti-institutional cohortHER2-positive tumorsSerous carcinomaOverall survivalHER2 overexpressionStage ILymph-vascular space invasionHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Epidermal growth factor 2Endometrial cancer deathsHER2-positive cohortHER2-positive diseaseStage IB diseaseBreast cancer guidelinesGrowth factor receptor 2HER2-negative tumorsWorse survival outcomesKaplan-Meier analysisBody mass indexPoor prognostic tumorSelection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma
Pelligra S, Buza N, Hui P, Bellone S, Zeybek B, Ratner E, Schwartz PE, Scambia G, Santin AD. Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma. Gynecologic Oncology Reports 2020, 32: 100554. PMID: 32140533, PMCID: PMC7049633, DOI: 10.1016/j.gore.2020.100554.Peer-Reviewed Original ResearchUterine serous carcinomaHER2/neuNegative tumor cellsUSC patientsTumor cellsSerous carcinomaHER2/neu overexpressionCarboplatin/paclitaxelInitial clinical responsePost-treatment biopsiesHumanized monoclonal antibodyC-erbB2 gene amplificationNCCN guidelinesClinical responseEndometrial cancerPreferred regimenAggressive variantMechanisms of resistanceNeu overexpressionRecurrent/HER2/TrastuzumabPatientsMonoclonal antibodiesNeu
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
2009
Potential therapeutic activity of adecatumumab (MT201), a fully human monoclonal antibody, against epithelial cell adhesion molecule (EpCAM) in uterine serous papillary carcinoma
Santin A, Bellone S, El-Sahwi K, Buza N, Tavassoli F, Silasi D, Azodi M, Schwartz P, Rutherford T, Pecorelli S. Potential therapeutic activity of adecatumumab (MT201), a fully human monoclonal antibody, against epithelial cell adhesion molecule (EpCAM) in uterine serous papillary carcinoma. Journal Of Clinical Oncology 2009, 27: e16502-e16502. DOI: 10.1200/jco.2009.27.15_suppl.e16502.Peer-Reviewed Original ResearchUterine serous papillary carcinomaPrimary USPC cell linesAntibody-dependent cellular cytotoxicityUSPC cell linesNormal endometrial cellsSerous papillary carcinomaComplement-dependent cytotoxicityHuman monoclonal antibodyEpithelial cell adhesion moleculeEndometrial cellsCell adhesion moleculePapillary carcinomaTherapeutic strategiesCell linesChromium release cytotoxicity assaysFlow cytometryEpCAM expressionMonoclonal antibodiesDependent cytotoxicityAdhesion moleculesRelease cytotoxicity assayStandard treatment modalityDependent cellular cytotoxicityUterine serous carcinomaAggressive biologic behavior