PURPOSE: In breast cancer, the PIK3CA gene is frequently mutated at "hotspots" in exons 9 and 20, corresponding to the helical and kinase domains, respectively. We decided to investigate the association of PIK3CA mutations with pathologic features and clinical outcome in a large series of patients with breast cancer. EXPERIMENTAL DESIGN: Frozen samples from 163 consecutive patients were analyzed for PIK3CA mutations using PCR single-strand conformation polymorphism and sequence analyses. RESULTS: We identified 46 missense mutations, 24 (53%) in exon 9, and 21 (47%) in exon 20. Twelve (50%) of the 24 mutations in exon 9 were of the E542K type and 11 (46%) were of the E545K type. Twenty (95%) of the 21 mutations in exon 20 were H1047R substitutions. Mutations in exon 9 were more frequent in lobular carcinomas (42% of cases) than in ductal carcinoma (11% of cases; P = 0.002). At univariate survival analysis, PIK3CA exon 20 mutations were associated with prolonged overall and disease-free survival, whereas mutations in exon 9 were associated with significantly worse prognosis. At multivariate analysis, exon 9 PIK3CA mutations were the strongest independent factor to predict poor prognosis for disease-free survival (P = 0.0003) and overall survival (P = 0.001). CONCLUSION: Our data show that exon 9 PIK3CA mutations are typical of infiltrating lobular carcinomas. In addition, they indicate that PIK3CA mutations in different exons are of different prognostic value: exon 9 mutations are independently associated with early recurrence and death, whereas exon 20 PIK3CA mutations are associated with optimal prognosis.
PURPOSE: In breast cancer, the PIK3CA gene is frequently mutated at "hotspots" in exons 9 and 20, corresponding to the helical and kinase domains, respectively. We decided to investigate the association of PIK3CA mutations with pathologic features and clinical outcome in a large series of patients with breast cancer. EXPERIMENTAL DESIGN: Frozen samples from 163 consecutive patients were analyzed for PIK3CA mutations using PCR single-strand conformation polymorphism and sequence analyses. RESULTS: We identified 46 missense mutations, 24 (53%) in exon 9, and 21 (47%) in exon 20. Twelve (50%) of the 24 mutations in exon 9 were of the E542K type and 11 (46%) were of the E545K type. Twenty (95%) of the 21 mutations in exon 20 were H1047R substitutions. Mutations in exon 9 were more frequent in lobular carcinomas (42% of cases) than in ductal carcinoma (11% of cases; P = 0.002). At univariate survival analysis, PIK3CA exon 20 mutations were associated with prolonged overall and disease-free survival, whereas mutations in exon 9 were associated with significantly worse prognosis. At multivariate analysis, exon 9 PIK3CA mutations were the strongest independent factor to predict poor prognosis for disease-free survival (P = 0.0003) and overall survival (P = 0.001). CONCLUSION: Our data show that exon 9 PIK3CA mutations are typical of infiltrating lobular carcinomas. In addition, they indicate that PIK3CA mutations in different exons are of different prognostic value: exon 9 mutations are independently associated with early recurrence and death, whereas exon 20 PIK3CA mutations are associated with optimal prognosis.
Authors: Haijun Zhang; Di Chen; Jonathan Ringler; Wei Chen; Qiuzhi Cindy Cui; Stephen P Ethier; Q Ping Dou; Guojun Wu Journal: Cancer Res Date: 2010-04-27 Impact factor: 12.701
Authors: Sherene Loi; Benjamin Haibe-Kains; Samira Majjaj; Francoise Lallemand; Virginie Durbecq; Denis Larsimont; Ana M Gonzalez-Angulo; Lajos Pusztai; W Fraser Symmans; Alberto Bardelli; Paul Ellis; Andrew N J Tutt; Cheryl E Gillett; Bryan T Hennessy; Gordon B Mills; Wayne A Phillips; Martine J Piccart; Terence P Speed; Grant A McArthur; Christos Sotiriou Journal: Proc Natl Acad Sci U S A Date: 2010-05-17 Impact factor: 11.205
Authors: Arantza Fariña Sarasqueta; Eliane C M Zeestraten; Tom van Wezel; Gesina van Lijnschoten; Ronald van Eijk; Jan Willem T Dekker; Peter J K Kuppen; Ines J Goossens-Beumer; Valery E P P Lemmens; Cornelis J H van de Velde; Harm J T Rutten; Hans Morreau; A J C van den Brule Journal: Cell Oncol (Dordr) Date: 2011-08-10 Impact factor: 6.730
Authors: Stefan S Bozhanov; Svetla G Angelova; Maria E Krasteva; Tsanko L Markov; Svetlana L Christova; Ivan G Gavrilov; Elena I Georgieva Journal: J Cancer Res Clin Oncol Date: 2010-02-23 Impact factor: 4.553
Authors: Huan Pang; Rory Flinn; Antonia Patsialou; Jeffrey Wyckoff; Evanthia T Roussos; Haiyan Wu; Maria Pozzuto; Sumanta Goswami; John S Condeelis; Anne R Bresnick; Jeffrey E Segall; Jonathan M Backer Journal: Cancer Res Date: 2009-11-10 Impact factor: 12.701