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

Authors
 Katherine L. Pogue-Geile  ;  Nan Song  ;  Jong-Hyeon Jeong  ;  Patrick G. Gavin  ;  Seong-Rim Kim  ;  Nicole L. Blackmon  ;  Melanie Finnigan  ;  Priya Rastogi  ;  Louis Fehrenbacher  ;  Eleftherios P. Mamounas  ;  Sandra M. Swain  ;  D. Lawrence Wickerham  ;  Charles E. Geyer  ;  Joseph P. Costantino  ;  Norman Wolmark  ;  Soonmyung Paik 
Citation
 Journal of Clinical Oncology, Vol.33(12) : 1340-1347, 2015 
Journal Title
 Journal of Clinical Oncology 
ISSN
 0732-183X 
Issue Date
2015
Abstract
PURPOSE: 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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141399
DOI
10.1200/JCO.2014.56.2439
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
백순명(Paik, Soon Myung)
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Full Text
http://jco.ascopubs.org/content/33/12/1340.abstract
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