Breast Cancer Research and Treatment

, Volume 96, Issue 1, pp 91–95

PIK3CA mutations in breast cancer are associated with poor outcome

  • Shao Ying Li
  • Minna Rong
  • Fabienne Grieu
  • Barry Iacopetta
Original Report

Summary

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).

Keywords

AKT breast cancer erbB2 estrogen receptor mutations PI3K prognosis 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Vivanco I, Sawyers CL, The phosphatidylinositol-3-Kinase AKT pathway in human cancer Nat Rev Cancer 2: 489–501, 2002CrossRefPubMedGoogle Scholar
  2. 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
  3. 3.
    Bellacosa A, de Feo D, Godwin AK, Bell DW, Cheng JQ, Altomare DA, Wan M, Dubeau L, Scambia G, Masciullo V, et al. Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas Int J Cancer 64: 280–285, 1995PubMedCrossRefGoogle Scholar
  4. 4.
    Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C, Pinkel D, Powell B, Mills GB, Gray JW, PIK3CA is implicated as an oncogene in ovarian cancer Nat Genet 21: 99–102, 1999CrossRefPubMedGoogle Scholar
  5. 5.
    Saito M, Okamoto A, Kohno T, Takakura S, Shinozaki H, Isonishi S, Yasuhara T, Yoshimura T, Ohtake Y, Ochiai K, Yokota J, Tanaka T, Allelic imbalance and mutations of the PTEN gene in ovarian cancer Int J Cancer 85: 160–165, 2000PubMedGoogle Scholar
  6. 6.
    Philp AJ, Campbell IG, Leet C, Vincan E, Rockman SP, Whitehead RH, Thomas RJ, Phillips WA, The phosphatidylinositol-3′-kinase p85alpha gene is an oncogene in human ovarian and colon tumors Cancer Res 61: 7426–7429, 2001PubMedGoogle Scholar
  7. 7.
    Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE, High frequency of mutations of the PIK3CA gene in human cancers Science 304: 554, 2004CrossRefPubMedGoogle Scholar
  8. 8.
    Lee JW, Soung YH, Kim SY, Lee HW, Park WS, Nam SW, Kim SH, Lee JY, Yoo NJ, Lee SH, PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomas Oncogene 24: 1477–1480, 2005CrossRefPubMedGoogle Scholar
  9. 9.
    Campbell IG, Russell SE, Choong DY, Montgomery KG, Ciavarella ML, Hooi CS, Cristiano BE, Pearson RB, Phillips WA, Mutation of the PIK3CA gene in ovarian and breast cancer Cancer Res 64: 7678–7681, 2004 CrossRefPubMedGoogle Scholar
  10. 10.
    Bachman KE, Argani P, Samuels Y, Silliman N, Ptak J, Szabo S, Konishi H, Karakas B, Blair BG, Lin C, Peters BA, Velculescu VE, Park BH, The PIK3CA gene is mutated with high frequency in human breast cancers Cancer Biol Ther 3: 772–775, 2004PubMedCrossRefGoogle Scholar
  11. 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
  12. 12.
    Levine DA, Bogomolniy F, Yee CJ, Lash A, Barakat RR, Borgen PI, Boyd J, Frequent mutation of the PIK3CA gene in ovarian and breast cancers Clin Cancer Res 11: 2875–2878, 2005CrossRefPubMedGoogle Scholar
  13. 13.
    Wang Y, Helland A, Holm R, Kristensen GB, Borresen-Dale AL, PIK3CA mutations in advanced ovarian carcinomas Hum Mutat 25: 322, 2005CrossRefPubMedGoogle Scholar
  14. 14.
    Grieu F, Li WQ, Iacopetta B, Genetic polymorphisms in the MMP-2 and MMP-9 genes and breast cancer phenotype Breast Cancer Res Treat 88: 197–204, 2004CrossRefPubMedGoogle Scholar
  15. 15.
    Iacopetta B, Elsaleh H, Grieu F, Joseph D, Sterrett G, Robbins P, Routine analysis of p53 mutation in clinical breast tumor specimens using fluorescence-based polymerase chain reaction and single strand conformation polymorphism Diagn Mol Pathol 9: 20–25, 2000CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2005

Authors and Affiliations

  • Shao Ying Li
    • 1
  • Minna Rong
    • 1
  • Fabienne Grieu
    • 1
  • Barry Iacopetta
    • 1
    • 2
  1. 1.School of Surgery and PathologyUniversity of Western AustraliaNedlandsAustralia
  2. 2.School of Surgery and PathologyUniversity of Western Australia NedlandsAustralia

Personalised recommendations