title: PIK3CA mutations define favorable prognostic biomarkers in operable breast cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  Mutations of the p110α catalytic subunit of phosphatidylinositol 3-kinase (PIK3CA) are among the most common genetic aberrations in human breast cancer. At present, controversy exists concerning the prognostic value of the mutations.
  
  
  METHODS
  We performed a systematic review and meta-analysis to clarify the association between PIK3CA mutations and survival outcomes. A comprehensive, computerized literature search of PubMed, Web of Science databases, the Chinese Biomedical Literature Database, and Wangfang Data until August 27, 2013 was carried out. Eligible studies were included according to specific inclusion criteria. Pooled hazard ratio was estimated by using the fixed effects model or random effects model according to heterogeneity between studies.
  
  
  RESULTS
  Eight eligible studies were included in the analysis, all of which were retrospective cohort studies. The overall meta-analysis demonstrated that the PIK3CA mutations were associated with better clinical outcomes (hazard ratio 0.72; 95% confidence interval: 0.57-0.91; P=0.006). None of the single studies materially altered the original results and no evidence of publication bias was found. Further subgroup analysis of mutations in exons 9 and 20 did not show statistical significance.
  
  
  CONCLUSIONS
  PIK3CA mutations in operable primary breast cancer indicate a good prognosis. Further studies should be conducted to investigate the effect of PIK3CA mutations on clinical outcomes in different histologic types, different molecular subtypes of breast cancer, and different exons of PIK3CA.
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yi-Rong
authors.initials: YR
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Jiang
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Wen-Jia
authors.initials: WJ
authors.lastname: Zuo
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ke-Da
authors.initials: KD
authors.lastname: Yu
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
keywords: early breast cancer; p110g catalytic subunit of phosphatidylinositol 3-kinase; prognosis; somatic mutations
references.citation: Control Clin Trials. 1986 Sep;7(3):177-88
references.pmid: 3802833
references.citation: J Clin Oncol. 2009 May 1;27(13):2278-87
references.pmid: 19332717
references.citation: Annu Rev Pathol. 2009;4:127-50
references.pmid: 18767981
references.citation: Clin Cancer Res. 2009 Aug 15;15(16):5049-59
references.pmid: 19671852
references.citation: Cancer Res. 2004 Nov 1;64(21):7678-81
references.pmid: 15520168
references.citation: Nat Rev Drug Discov. 2005 Dec;4(12):988-1004
references.pmid: 16341064
references.citation: Diagn Mol Pathol. 2009 Dec;18(4):200-5
references.pmid: 19861897
references.citation: Cancer Discov. 2012 Mar;2(3):248-59
references.pmid: 22585995
references.citation: Mol Cell. 2010 May 14;38(3):333-44
references.pmid: 20471940
references.citation: Curr Opin Investig Drugs. 2010 Jun;11(6):615-28
references.pmid: 20496256
references.citation: Clin Cancer Res. 2007 Oct 15;13(20):6064-9
references.pmid: 17947469
references.citation: Ann Surg Oncol. 2008 Apr;15(4):1064-9
references.pmid: 18183466
references.citation: J Natl Cancer Inst. 2013 Mar 20;105(6):393-404
references.pmid: 23355761
references.citation: Nature. 2006 May 25;441(7092):424-30
references.pmid: 16724053
references.citation: Cell Cycle. 2006 Mar;5(6):603-5
references.pmid: 16582622
references.citation: Breast Cancer Res. 2012 Feb 13;14(1):R28
references.pmid: 22330809
references.citation: Cancer Biol Ther. 2004 Aug;3(8):772-5
references.pmid: 15254419
references.citation: Curr Top Microbiol Immunol. 2010;347:21-41
references.pmid: 20535651
references.citation: Clinics (Sao Paulo). 2012 Nov;67(11):1285-90
references.pmid: 23184205
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10208-13
references.pmid: 20479250
references.citation: J Cancer Res Clin Oncol. 2010 Nov;136(11):1657-69
references.pmid: 20177704
references.citation: Breast Cancer Res Treat. 2013 May;139(1):39-49
references.pmid: 23592373
references.citation: Ann Oncol. 2012 Aug;23(8):2034-2042
references.pmid: 22172323
references.citation: Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):408-14
references.pmid: 17202311
references.citation: Science. 2004 Apr 23;304(5670):554
references.pmid: 15016963
references.citation: Mol Biol Rep. 2012 Dec;39(12):11153-65
references.pmid: 23054001
references.citation: Breast Cancer Res Treat. 2012 Feb;132(1):29-39
references.pmid: 21512767
references.citation: Nat Rev Cancer. 2005 Dec;5(12):921-9
references.pmid: 16341083
references.citation: BMC Cancer. 2008 May 29;8:153
references.pmid: 18510726
references.citation: Breast Cancer Res Treat. 2012 Feb;132(1):51-9
references.pmid: 21533532
references.citation: Breast Cancer Res Treat. 2006 Mar;96(1):91-5
references.pmid: 16317585
references.citation: Cancer Res. 2005 Apr 1;65(7):2554-9
references.pmid: 15805248
references.citation: Breast Cancer Res Treat. 2010 Jul;122(1):45-53
references.pmid: 19701705
references.citation: Breast Cancer Res Treat. 2013 Jun;139(2):329-39
references.pmid: 23670132
references.citation: J Cell Mol Med. 2010 Apr;14(4):944-53
references.pmid: 19298520