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Genomic Profiling of Premenopausal HR+ and HER2- Metastatic Breast Cancer by Circulating Tumor DNA and Association of Genetic Alterations With Therapeutic Response to Endocrine Therapy and Ribociclib

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dc.contributor.author손주혁-
dc.date.accessioned2022-09-14T01:29:12Z-
dc.date.available2022-09-14T01:29:12Z-
dc.date.issued2021-08-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/190475-
dc.description.abstractPurpose: This analysis evaluated the genomic landscape of premenopausal patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer and the association of genetic alterations with response to ribociclib in the phase III MONALEESA-7 trial. Methods: Premenopausal patients were randomly assigned 1:1 to receive endocrine therapy plus ribociclib or placebo. Plasma collected at baseline was sequenced using targeted next-generation sequencing for approximately 600 relevant cancer genes. The association of circulating tumor DNA alterations with progression-free survival (PFS) was evaluated to identify biomarkers of response and resistance to ribociclib. Results: Baseline circulating tumor DNA was sequenced in 565 patients; 489 had evidence of ≥ 1 alteration. The most frequent alterations included PIK3CA (28%), TP53 (19%), CCND1 (10%), MYC (8%), GATA3 (8%), receptor tyrosine kinases (17%), and the Chr8p11.23 locus (12%). A treatment benefit of ribociclib was seen with wild-type (hazard ratio [HR] 0.45 [95% CI, 0.33 to 0.62]) and altered (HR 0.57 [95% CI, 0.36 to 0.9]) PIK3CA. Overall, patients with altered CCND1 had shorter PFS regardless of treatment, suggesting CCND1 as a potential prognostic biomarker. Benefit with ribociclib was seen in patients with altered (HR 0.21 [95% CI, 0.08 to 0.54]) or wild-type (HR 0.52 [95% CI, 0.39 to 0.68]) CCND1, but greater benefit was observed with altered, suggesting predictive potential of CCND1. Alterations in TP53, MYC, Chr8p11.23 locus, and receptor tyrosine kinases were associated with worse PFS, but ribociclib benefit was independent of alteration status. Conclusion: In this study-to our knowledge, the first large study of premenopausal patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer-multiple genomic alterations were associated with poor outcome. A PFS benefit of ribociclib was observed regardless of gene alteration status, although in this exploratory analysis, a magnitude of benefits varied by alteration.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherAmerican Society of Clinical Oncology-
dc.relation.isPartOfJCO PRECISION ONCOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAdolescent-
dc.subject.MESHAdult-
dc.subject.MESHAminopyridines / administration & dosage*-
dc.subject.MESHAntineoplastic Agents, Hormonal / administration & dosage*-
dc.subject.MESHAntineoplastic Combined Chemotherapy Protocols / therapeutic use-
dc.subject.MESHBiomarkers, Tumor / genetics-
dc.subject.MESHBreast Neoplasms / drug therapy*-
dc.subject.MESHBreast Neoplasms / genetics*-
dc.subject.MESHBreast Neoplasms / mortality-
dc.subject.MESHBreast Neoplasms / pathology-
dc.subject.MESHCirculating Tumor DNA / genetics*-
dc.subject.MESHDouble-Blind Method-
dc.subject.MESHDrug Resistance, Neoplasm / genetics-
dc.subject.MESHFemale-
dc.subject.MESHGenomics-
dc.subject.MESHHumans-
dc.subject.MESHMiddle Aged-
dc.subject.MESHPremenopause / drug effects-
dc.subject.MESHProgression-Free Survival-
dc.subject.MESHProportional Hazards Models-
dc.subject.MESHPurines / administration & dosage*-
dc.subject.MESHReceptor, ErbB-2 / genetics-
dc.subject.MESHTranscription Factors / genetics-
dc.subject.MESHYoung Adult-
dc.titleGenomic Profiling of Premenopausal HR+ and HER2- Metastatic Breast Cancer by Circulating Tumor DNA and Association of Genetic Alterations With Therapeutic Response to Endocrine Therapy and Ribociclib-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorAditya Bardia-
dc.contributor.googleauthorFei Su-
dc.contributor.googleauthorNadia Solovieff-
dc.contributor.googleauthorSeock-Ah Im-
dc.contributor.googleauthorJoohyuk Sohn-
dc.contributor.googleauthorKeun Seok Lee-
dc.contributor.googleauthorSaul Campos-Gomez-
dc.contributor.googleauthorKyung Hae Jung-
dc.contributor.googleauthorMarco Colleoni-
dc.contributor.googleauthorRafael Villanueva Vázquez-
dc.contributor.googleauthorFabio Franke-
dc.contributor.googleauthorSara Hurvitz-
dc.contributor.googleauthorNadia Harbeck-
dc.contributor.googleauthorLouis Chow-
dc.contributor.googleauthorTetiana Taran-
dc.contributor.googleauthorKaren Rodriguez Lorenc-
dc.contributor.googleauthorNaveen Babbar-
dc.contributor.googleauthorDebu Tripathy-
dc.contributor.googleauthorYen-Shen Lu-
dc.identifier.doi10.1200/PO.20.00445-
dc.contributor.localIdA01995-
dc.relation.journalcodeJ04289-
dc.identifier.eissn2473-4284-
dc.identifier.pmid34504990-
dc.contributor.alternativeNameSohn, Joo Hyuk-
dc.contributor.affiliatedAuthor손주혁-
dc.citation.volume5-
dc.citation.startPage1408-
dc.citation.endPage1420-
dc.identifier.bibliographicCitationJCO PRECISION ONCOLOGY, Vol.5 : 1408-1420, 2021-08-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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