Annotation Detail

Information
Associated Genes
PIK3CA
Associated Variants
PIK3CA p.His1047Arg (p.H1047R) ( ENST00000263967.4, ENST00000643187.1 )
PIK3CA p.His1047Arg (p.H1047R) ( ENST00000263967.4, ENST00000643187.1 )
Associated Disease
Her2-receptor positive breast cancer
Source Database
CIViC Evidence
Description
In a phase 3 clinical trial (NCT00829166), metastatic breast cancer patients with PIK3CA mutation (n=40), including patients with PIK3CA H1047R, treated with ado-trastuzumab were associated with improved median progression free survival (10.9 vs. 9.8 months), as compared to patients with wild-type PIK3CA (n=93). Further, the patients harboring PIK3CA mutations (n=79) were associated with a decrease in disease progression (ado-trastuzumab relative to standard chemotherapy; HR:0.45; 95% CI:0.25-0.82), as compared to patients with wild-type PIK3CA (n=180; HR:0.74; 95% CI:0.50-1.10). In an in vitro study, HCC1954 and KPL-4 cell lines expressing PIK3CA H1047R mutation was associated with increased sensitivity to ado-trastuzumab emtansine treatment compared to trastuzumab treated HCC1954 and KPL-4 cells. Sensitivity was determined by assessing cell viability. Further, in an in vivo study, KPL-4 xenografts expressing PIK3CA H1047R were reportedly sensitive to ado-trastuzumab emtansine, as assessed by tumor growth.
Variant Origin
somatic
Variant Origin
Somatic
Evidence URL
https://civic.genome.wustl.edu/links/evidence_items/2103
Gene URL
https://civic.genome.wustl.edu/links/genes/37
Variant URL
https://civic.genome.wustl.edu/links/variants/107
Rating
3
Evidence Type
Predictive
Disease
Her2-receptor Positive Breast Cancer
Evidence Direction
Supports
Drug
Trastuzumab Emtansine
Evidence Level
B
Clinical Significance
Sensitivity/Response
Pubmed
26920887
Drugs
Drug NameSensitivitySupported
Trastuzumab EmtansineSensitivitytrue