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Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients.

Prevalence and Prognostic Role of PIK3CA/AKT1 Mutations in Chinese Breast Cancer Patients.
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Deng L, Zhu X, Sun Y, Wang J, Zhong X, Li J, Hu M, Zheng H,


Deng L, Zhu X, Sun Y, Wang J, Zhong X, Li J, Hu M, Zheng H, (click to view)

Deng L, Zhu X, Sun Y, Wang J, Zhong X, Li J, Hu M, Zheng H,

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Cancer research and treatment : official journal of Korean Cancer Association 2018 03 15() doi 10.4143/crt.2017.598

Abstract
Purpose
The prevalence of PIK3CA in Chinese breast cancer patients may be underestimated. Therefore, we investigated the distribution of somatic PIK3CA/AKT1 mutations in Chinese breast cancer patients and explored their roles in tumor phenotypes and disease prognosis.

Materials and Methods
Tumors from five hundred and seven breast cancer patients were prospectively collected from the West China Hospital between 2008 and 2013. Whole exons of AKT1 and PIK3CA were detected in fresh-frozen tumors using next-generation sequencing, and correlations between PIK3CA/AKT1 mutations and clinicopathological features were analyzed.

Results
The AKT1 mutation was found in 3.6% (18/507) of patients. Tumors from patients that carried the AKT1 mutation were estrogen receptor (ER)+/progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2)‒ and were more likely to have high expression levels of Ki67. The prevalence of the PIK3CA mutation was 46.5% (236/507), and 35 patients carried two or three variants of the PIK3CA gene. PIK3CA mutations were associated with ER+/PR+/HER2‒ status. The prognosis of patients with one mutation in PIK3CA (or PIK3CA/AKT1) was not significantly different than that of patients with wild-type PIK3CA (or PIK3CA/AKT1), while patients with two or three variants in PIK3CA (or PIK3CA/AKT1) exhibited poorer outcomes in the entire group and in all three subgroups (ER+, HER2‒, Ki67 high), particularly with respect to overall survival.

Conclusion
A high frequency of somatic PIK3CA mutations was detected in Chinese breast cancer patients. In addition to the mutation frequency, the tumor mutational burden of the PIK3CA and AKT1 genes should also be of concern, as they may be associated with poor prognosis.

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