PIK3CA mutations in breast cancer are associated with poor outcome
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The phosphatidylinositol-3-kinase (PI3K)–AKT signaling pathway is considered to play an important role in tumorigenesis. Frequent somatic mutations in the PI3K subunit p110α (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).
KeywordsAKT breast cancer erbB2 estrogen receptor mutations PI3K prognosis
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The authors are grateful to Dr Ian Campbell for information on primer sequences.
- 2.Sun M, Wang G, Paciga JE, Feldman RI, Yuan ZQ, Ma XL, Shelley SA, Jove R, Tsichlis PN, Nicosia SV, Cheng JQ, AKT1/PKBalpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells Am J Pathol 159: 431–437, 2001PubMedGoogle Scholar
- 11.Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, Yu JS, Malmstrom PO, Mansukhani M, Enoksson J, Hibshoosh H, Borg A, Parsons R, PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma Cancer Res 65: 2554–2559, 2005CrossRefPubMedGoogle Scholar