Journal of Clinical & Experimental Pathology
Open Access

Research Article

PIK3CA/AKT1 Mutations in Breast Carcinoma: a Comprehensive Review of Experimental and Clinical Studies

Department of Pathology and Knight Cancer Institute, Oregon Health & Science University, USA

*Corresponding Author:

Megan L. Troxell
Department of Pathology, L471
3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA
Tel: 503-418-1770
Fax: 503-494-8148
E-mail: troxellm@ohsu.edu

Received Date: November 21, 2011; Accepted Date: January 27, 2012; Published Date: January 30, 2012

Citation: Troxell ML (2012) PIK3CA/AKT1 Mutations in Breast Carcinoma: a Comprehensive Review of Experimental and Clinical Studies. J Clin Exp Pathol S1:002. doi: 10.4172/2161-0681.S1-002

Copyright: © 2012 Troxell ML. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The phosphatidylinositol-3-kinase (PI3K) pathway is an important nexus for integration of extracellular and intracellular signals, and there are very frequent perturbations of this pathway in breast cancer, making it an attractive target for therapeutic manipulation. Hotspot mutations in PIK3CA or AKT1 are found in nearly 30% of breast cancers, especially estrogen receptor-positive and Her-2/neu-positive subgroups. This review will emphasize experimental models, clinical characterization and implications of PIK3CA/AKT1 mutations in breast cancer. In vitro studies have demonstrated that these mutations are kinase-activating and can confer cellular transforming properties in the correct context. Further, overexpression of PIK3CA H1047R in a variety of murine models results in mammary proliferation and carcinomas, and established carcinomas may become PIK3CA H1047R-independent. Data from human breast carcinomas regarding the clinicopathologic significance of PIK3CA/AKT1 mutations were contradictory at first, yet trends are beginning to emerge. PIK3CA mutation seems to impart a favorable prognosis in estrogen-receptor positive breast cancers, and mutations are seen early, in pre-invasive breast lesions. Although larger studies are needed, PIK3CA mutations may not confer selective advantage in the metastatic setting. Numerous pharmacologic compounds targeting the PI3K pathway are in development. The complexity of PI3K crosstalk with other signaling cascades, negative feedback regulation, and the myriad of other genotypic and phenotypic deviations in breast cancers argues for thorough molecular characterization of tumors in cancer trials.