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Intrinsic subtypes, PIK3CA mutation, and the degree of benefit from adjuvant trastuzumab in the NSABP B-31 trial

DC FieldValueLanguage
dc.contributor.author백순명-
dc.date.accessioned2016-02-04T11:52:38Z-
dc.date.available2016-02-04T11:52:38Z-
dc.date.issued2015-
dc.identifier.issn0732-183X-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/141399-
dc.description.abstractPURPOSE: Considerable molecular heterogeneity exists among human epidermal growth factor receptor 2 (HER2) -positive breast cancer regarding gene expression and mutation profiling. Evidence from preclinical, clinical neoadjuvant, and metastatic clinical trials suggested that PIK3CA mutational status and PAM50 intrinsic subtype of a tumor were markers of response to anti-HER2 therapies. We evaluated the predictive value of these two biomarkers in the adjuvant setting using archived tumor blocks from National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-31. PATIENTS AND METHODS: Expression data for 49 genes using the nCounter platform were used to generate PAM50 intrinsic subtypes for 1,578 archived tumor blocks from patients in the B-31 trial. Six PIK3CA hotspot mutations were examined by mass spectrometry of the primer extension products in a randomly selected subset (n = 671). We examined the heterogeneity of trastuzumab treatment effect across different subsets defined by each marker using Cox regression and disease-free survival as the end point. RESULTS: Seven hundred forty-one (47.0%) of 1,578 tumors were classified as HER2-enriched (HER2E) subtype, and 166 (24.7%) of 671 tumors had PIK3CA mutations. Hazard ratios (HRs) for trastuzumab in HER2E and other subtypes were 0.44 (95% CI, 0.34 to 0.58; P < .001) and 0.47 (95% CI, 0.35 to 0.62; P < .001), respectively (interaction P = .67). HRs for trastuzumab in PIK3CA wild-type and mutated tumors were 0.51 (95% CI, 0.37 to 0.71; P < .001) and 0.44 (95% CI, 0.24 to 0.82; P = .009), respectively (interaction P = .64). CONCLUSION: Unlike results seen in the metastatic and neoadjuvant clinical trials, PIK3CA and PAM50 intrinsic subtypes were not predictive biomarkers for adjuvant trastuzumab in NSABP B-31. These data suggest that results from the metastatic and neoadjuvant setting may not be always applicable to the adjuvant setting.-
dc.description.statementOfResponsibilityopen-
dc.format.extent1340~1347-
dc.relation.isPartOfJOURNAL OF CLINICAL ONCOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleIntrinsic subtypes, PIK3CA mutation, and the degree of benefit from adjuvant trastuzumab in the NSABP B-31 trial-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Life Science (의생명과학부)-
dc.contributor.googleauthorKatherine L. Pogue-Geile-
dc.contributor.googleauthorNan Song-
dc.contributor.googleauthorJong-Hyeon Jeong-
dc.contributor.googleauthorPatrick G. Gavin-
dc.contributor.googleauthorSeong-Rim Kim-
dc.contributor.googleauthorNicole L. Blackmon-
dc.contributor.googleauthorMelanie Finnigan-
dc.contributor.googleauthorPriya Rastogi-
dc.contributor.googleauthorLouis Fehrenbacher-
dc.contributor.googleauthorEleftherios P. Mamounas-
dc.contributor.googleauthorSandra M. Swain-
dc.contributor.googleauthorD. Lawrence Wickerham-
dc.contributor.googleauthorCharles E. Geyer-
dc.contributor.googleauthorJoseph P. Costantino-
dc.contributor.googleauthorNorman Wolmark-
dc.contributor.googleauthorSoonmyung Paik-
dc.identifier.doi10.1200/JCO.2014.56.2439-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01823-
dc.relation.journalcodeJ01331-
dc.identifier.eissn1527-7755-
dc.identifier.urlhttp://jco.ascopubs.org/content/33/12/1340.abstract-
dc.contributor.alternativeNamePaik, Soon Myung-
dc.contributor.affiliatedAuthorPaik, Soon Myung-
dc.rights.accessRightsnot free-
dc.citation.volume33-
dc.citation.number12-
dc.citation.startPage1340-
dc.citation.endPage1347-
dc.identifier.bibliographicCitationJOURNAL OF CLINICAL ONCOLOGY, Vol.33(12) : 1340-1347, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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