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 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