PIK3CA mutations in breast cancer are associated with poor outcome.
The phosphatidylinositol-3-kinase (PI3K)-AKT signaling pathway is considered to play an important role in tumorigenesis. Frequent somatic mutations in the PI3K subunit p110alpha (PIK3CA) occur in a variety of cancer types. We screened 250 primary human breast tumors for mutations in PIK3CA in order to determine associations with pathological features and with patient outcome. The frequency of PIK3CA mutations in the C2, helical and kinase domains was 35% (88/250). Mutations were associated with larger tumor size (p = 0.004) and positive estrogen receptor status (p = 0.008). Patients with PIK3CA mutations showed significantly worse survival (p = 0.004), particularly those with positive estrogen receptor expression or non-amplified erbB2 (both p = 0.002). PIK3CA mutation was an independent factor for worse survival in breast cancer patients with non-amplified erbB2 (RR = 2.6, 95%CI [1.2-5.5], p = 0.016).
Li
Shao Ying
SY
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia.
Rong
Minna
M
Grieu
Fabienne
F
Iacopetta
Barry
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000628:therapy; D002454:Cell Differentiation; D058534:Class I Phosphatidylinositol 3-Kinases; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016896:Treatment Outcome
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human