2022
Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers
Batalini F, Gulhan DC, Mao V, Tran A, Polak M, Xiong N, Tayob N, Tung NM, Winer EP, Mayer EL, Knappskog S, Lønning PE, Matulonis UA, Konstantinopoulos PA, Solit DB, Won H, Eikesdal HP, Park PJ, Wulf GM. Mutational Signature 3 Detected from Clinical Panel Sequencing is Associated with Responses to Olaparib in Breast and Ovarian Cancers. Clinical Cancer Research 2022, 28: of1-of10. PMID: 36048535, PMCID: PMC9623231, DOI: 10.1158/1078-0432.ccr-22-0749.Peer-Reviewed Original ResearchConceptsHomologous recombination deficiencyTriple-negative breast cancerMutational signature 3Ovarian cancerImproved progression-free survivalPARP inhibitorsPanel sequencingHigh-grade serous ovarian cancerPI3K inhibitor buparlisibPhase Ib trialProgression-free survivalIdentification of patientsRoutine clinical careSignature 3Serous ovarian cancerPARP inhibitor olaparibSame patient sampleIb trialObjective responseTNBC patientsBreast cancerBRCA1/2 mutationsClinical careInstability scoreGenomic instability score
2020
TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.
Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. Journal Of Clinical Oncology 2020, 38: 4274-4282. PMID: 33119476, DOI: 10.1200/jco.20.02151.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerObjective response rateProgression-free survivalPoly (ADP-ribose) polymerase (PARP) inhibitorsPhase II studyBreast cancerMutation carriersII studyMedian progression-free survivalNegative metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Clinical benefit rateHER2-negative diseasePlatinum-refractory diseaseGrowth factor receptor 2Population of patientsFactor receptor 2Homologous recombination-related genesConfirmed responsesEligible patientsMeasurable diseaseSecondary endpointsChemotherapy regimensPrimary endpointTBCRC 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 tissue
2018
Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer
Telli ML, Stover DG, Loi S, Aparicio S, Carey LA, Domchek SM, Newman L, Sledge GW, Winer EP. Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer. Breast Cancer Research And Treatment 2018, 171: 21-31. PMID: 29736741, DOI: 10.1007/s10549-018-4807-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsB7-H1 AntigenBiomarkers, TumorDisease SusceptibilityDNA DamageDNA RepairFemaleGene Expression Regulation, NeoplasticGenes, BRCA1Genes, BRCA2Germ-Line MutationHomologous RecombinationHumansImmunityImmunomodulationMolecular Targeted TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsHost anti-tumor immunityAnti-tumor immunityHomologous recombination deficiencyBreast cancerPurposeTriple-negative breast cancerAnti-tumor immune cellsRecombination deficiencyTriple-negative breast cancerCare systemic therapyImmune-directed therapiesImmune cell subsetsHomologous recombination DNA repair deficiencyBRCA2 mutation carriersBiomarker-driven approachBreast cancer subtypesPARP inhibitor olaparibHR-deficient tumorsDNA repair capacityMetastatic diseaseSystemic therapyImmune infiltratesImproved prognosisCell subsetsImmune cellsWorse outcomes
2016
Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer
Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, Szallasi Z, Barry WT, Winer EP, Tung NM, Isakoff SJ, Ryan PD, Greene-Colozzi A, Gutin A, Sangale Z, Iliev D, Neff C, Abkevich V, Jones JT, Lanchbury JS, Hartman AR, Garber JE, Ford JM, Silver DP, Richardson AL. Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer. Clinical Cancer Research 2016, 22: 3764-3773. PMID: 26957554, PMCID: PMC6773427, DOI: 10.1158/1078-0432.ccr-15-2477.Peer-Reviewed Original Research