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

 -  2015 
<br/><br/>Available online from MWHC library: 1999 - present, Available in print through MWHC library: 1999 - 2008 
<br/><br/> 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.Copyright � 2015 by American Society of Clinical Oncology.  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.  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.  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). 
<br/><br/><br/>English 
<br/><br/><label>ISSN: </label>0732-183X 
<br/><br/><label>Subjects--Topical Terms: </label><br/>*Antibodies, Monoclonal, Humanized/ad [Administration & Dosage]<br/>*Breast Neoplasms/dt [Drug Therapy]<br/>*Breast Neoplasms/ge [Genetics]<br/>*Mutation<br/>*Phosphatidylinositol 3-Kinases/ge [Genetics]<br/>Antineoplastic Agents/ad [Administration & Dosage]<br/>Breast Neoplasms/en [Enzymology]<br/>Breast Neoplasms/pa [Pathology]<br/>Chemotherapy, Adjuvant<br/>Disease-Free Survival<br/>Drug Resistance, Neoplasm<br/>Female<br/>Gene Expression Profiling<br/>Humans<br/>Neoplasm Staging<br/>Predictive Value of Tests<br/>Randomized Controlled Trials as Topic<br/>Receptor, ErbB-2<br/>Tumor Markers, Biological/ge [Genetics]
<br/><br/><label>Subjects--Geographic Terms: </label><br/>Washington Cancer Institute
<br/><br/><label>Index Terms--Function: </label><br/>Journal Article<br/>Research Support, N.I.H., Extramural<br/>Research Support, Non-U.S. Gov't