BACKGROUND: Prognostic factors that could select breast cancer patients with poor survival, and influence clinical trials of targeted therapy, are needed. However, the reported observations regarding the impact of PI3KCA mutation on breast cancers are controversial. METHODS: We analyzed exons 4, 7, 9, and 20 of PI3KCA on a series of 158 patients. Clinicopathological characteristics were correlated with the mutation data. RESULTS: Among 152 patients who were available for follow-up (median follow-up time, 6.57 years), 26% had PIK3CA mutations, more than half of which occurred in exon 20. The five-year survival rate of patients with exon 20 mutations (46%) was significantly lower than that of patients without (75%) (p = 0.0054). Multivariate analysis showed that PIK3CA exon 20 mutations and nodal involvement were independent risk factors for overall survival. The relative risk of death in patients with PIK3CA exon 20 mutations was 2.881 (95% CI, 1.406-5.900; p = 0.0038). CONCLUSIONS: PIK3CA mutations are common in invasive ductal carcinomas of the breast. Our result suggests that PIK3CA exon 20 mutation is an independent risk factor for poor prognosis in breast cancer patients, indicating that differences in patient numbers with PIK3CA exon 20 mutations in study and control arms should be avoided in clinical trials of PI3K inhibitors.
BACKGROUND: Prognostic factors that could select breast cancerpatients with poor survival, and influence clinical trials of targeted therapy, are needed. However, the reported observations regarding the impact of PI3KCA mutation on breast cancers are controversial. METHODS: We analyzed exons 4, 7, 9, and 20 of PI3KCA on a series of 158 patients. Clinicopathological characteristics were correlated with the mutation data. RESULTS: Among 152 patients who were available for follow-up (median follow-up time, 6.57 years), 26% had PIK3CA mutations, more than half of which occurred in exon 20. The five-year survival rate of patients with exon 20 mutations (46%) was significantly lower than that of patients without (75%) (p = 0.0054). Multivariate analysis showed that PIK3CA exon 20 mutations and nodal involvement were independent risk factors for overall survival. The relative risk of death in patients with PIK3CA exon 20 mutations was 2.881 (95% CI, 1.406-5.900; p = 0.0038). CONCLUSIONS:PIK3CA mutations are common in invasive ductal carcinomas of the breast. Our result suggests that PIK3CA exon 20 mutation is an independent risk factor for poor prognosis in breast cancerpatients, indicating that differences in patient numbers with PIK3CA exon 20 mutations in study and control arms should be avoided in clinical trials of PI3K inhibitors.
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: 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
Authors: Chang Hoon Song; So Yeon Park; Keun-Yong Eom; Jee Hyun Kim; Sung-Won Kim; Jae Sung Kim; In Ah Kim Journal: Breast Cancer Res Date: 2010-03-12 Impact factor: 6.466