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PIK3CA Exon 20 Mutation is Independently Associated with a Poor Prognosis in Breast Cancer Patients

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,...

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Published in:Annals of surgical oncology 2008-04, Vol.15 (4), p.1064-1069
Main Authors: Lai, Yuen-Liang, Mau, Bey-Liing, Cheng, Wen-Hsuan, Chen, Han-Ming, Chiu, Hsi-Hsiung, Tzen, Chin-Yuan
Format: Article
Language:English
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Summary: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.
ISSN:1068-9265
1534-4681
DOI:10.1245/s10434-007-9751-7