Annotation Detail

Information
Associated Genes
PIK3CA
Associated Variants
PIK3CA p.Glu545Lys (p.E545K) ( ENST00000263967.4, ENST00000643187.1 )
PIK3CA p.Glu545Lys (p.E545K) ( 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 E545K, 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, MCF7 cell lines expressing PIK3CA E545K mutation was associated with increased sensitivity to ado-trastuzumab emtansine treatment compared to trastuzumab treated MCF7 cells. Sensitivity was determined by assessing cell viability. Further, in an in vivo study, MCF7 xenografts expressing PIK3CA E545K 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/2036
Gene URL
https://civic.genome.wustl.edu/links/genes/37
Variant URL
https://civic.genome.wustl.edu/links/variants/104
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