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PI3K pathway activation in breast cancer is associated with the basal-like phenotype and cancer-specific mortality
Article first published online: 14 AUG 2009
DOI: 10.1002/ijc.24831
Copyright © 2009 UICC
Additional Information
How to Cite
López-Knowles, E., O'Toole, S. A., McNeil, C. M., Millar, E. K.A., Qiu, M. R., Crea, P., Daly, R. J., Musgrove, E. A. and Sutherland, R. L. (2010), PI3K pathway activation in breast cancer is associated with the basal-like phenotype and cancer-specific mortality. Int. J. Cancer, 126: 1121–1131. doi: 10.1002/ijc.24831
Publication History
- Issue published online: 27 DEC 2009
- Article first published online: 14 AUG 2009
- Accepted manuscript online: 14 AUG 2009 12:00AM EST
- Manuscript Accepted: 3 AUG 2009
- Manuscript Received: 10 MAY 2009
Funded by
- National Health and Medical Research Council of Australia (NHMRC)
- Cancer Institute NSW, Petre Foundation, RT Hall Trust
References
- 1, , , . Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer 2005; 5: 921–9.
- 2, , , , . Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 2005; 4: 988–1004.
- 3, , , , , , , , , , , , et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res 2008; 68: 6084–91.
- 4, , , , , , , , , , , , et al. PIK3CA-activating mutations and chemotherapy sensitivity in stage II-III breast cancer. Breast Cancer Res 2008; 10: R27.
- 5, , , , , , , . Exon 20 PIK3CA mutations decreases survival in aggressive (HER-2 positive) breast carcinomas. Virchows Arch 2008; 453: 133–9.
- 6, , , , , , , . PIK3CA mutations and PTEN loss correlate with similar prognostic factors and are not mutually exclusive in breast cancer. Clin Cancer Res 2007; 13: 3577–84.
- 7, , , , , , , . Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 2007; 67: 2643–8.
- 8, , , , , , , , , . Different prognostic roles of mutations in the helical and kinase domains of the PIK3CA gene in breast carcinomas. Clin Cancer Res 2007; 13: 6064–9.
- 9, , , , , . Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women. Clin Cancer Res 2007; 13: 408–14.
- 10, , , . PIK3CA mutations in breast cancer are associated with poor outcome. Breast Cancer Res Treat 2006; 96: 91–5.
- 11, , , , , , , , , , . PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma. J Pathol 2006; 208: 350–5.
- 12, , , , , , , , , , , . Somatic mutation and gain of copy number of PIK3CA in human breast cancer. Breast Cancer Res 2005; 7: R609–16.
- 13, , , , , , . Frequent mutation of the PIK3CA gene in ovarian and breast cancers. Clin Cancer Res 2005; 11: 2875–8.
- 14, , , , , , , , , , , , et al. PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Cancer Res 2005; 65: 2554–9.
- 15, , , , , , , , , , , , et al. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther 2004; 3: 772–5.
- 16, , , , , , , , . Mutation of the PIK3CA gene in ovarian and breast cancer. Cancer Res 2004; 64: 7678–81.
- 17, , , . The Akt pathway in human breast cancer: a tissue-array-based analysis. Mod Pathol 2006; 19: 238–45.
- 18, , . Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer. Mod Pathol 2001; 14: 672–6.
- 19, , , , , , , . Comparing the prognostic value of PTEN and Akt expression with the Mitotic Activity Index in adjuvant chemotherapy-treated node-negative breast cancer patients aged <55 years. Cell Oncol 2007; 29: 25–35.
- 20, , , , , . Reduced PTEN expression is associated with poor outcome and angiogenesis in invasive ductal carcinoma of the breast. Appl Immunohistochem Mol Morphol 2004; 12: 205–10.
- 21, , , , , , . Activation of the mTOR signaling pathway in breast cancer and its correlation with the clinicopathologic variables. Breast Cancer Res Treat 2008; 110: 477–83.
- 22, , , , , . The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome. J Pathol 2004; 204: 93–100.
- 23, , , , , , . Reduced expression of PTEN protein and its prognostic implications in invasive ductal carcinoma of the breast. Oncology 2005; 68: 398–404.
- 24, , , , . Comparison of Akt/mTOR signaling in primary breast tumors and matched distant metastases. Cancer 2008; 112: 2352–8.
- 25, , , , , , , , , , , , et al. Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer. Ann Oncol 2008; 19: 315–20.
- 26, , , , , , . AKT activation predicts outcome in breast cancer patients treated with tamoxifen. J Pathol 2005; 207: 139–46.
- 27, , , , , , , . 4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosis. Clin Cancer Res 2007; 13: 81–9.
- 28, , , , , , , , , , . Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients. Int J Cancer 2006; 118: 284–9.
- 29, , , , , , , , , , , , et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001; 98: 10869–74.
- 30, , , , , , , , , . Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA 2003; 100: 10393–8.
- 31, , , , , , , . Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 2008; 14: 1368–76.
- 32, , , , , , , , , , , . BAG-1 predicts patient outcome and tamoxifen responsiveness in ER-positive invasive ductal carcinoma of the breast. Br J Cancer 2009; 100: 123–33.
- 33, , , , , , . Validation of real-time RT-PCR for analysis of human breast cancer cell lines resistant or sensitive to treatment with antiestrogens. Endocr Relat Cancer 2003; 10: 409–18.
- 34, , , . PIK3CA alterations in primary (de novo) and secondary glioblastomas. Acta Neuropathol 2007; 113: 295–302.
- 35, , , , , , , , , , . Genomic and expression analysis of the 3q25-q26 amplification unit reveals TLOC1/SEC62 as a probable target gene in prostate cancer. Mol Cancer Res 2006; 4: 169–76.
- 36, , . Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling pathway independent of phosphatidylinositol 3′-kinase and Akt/protein kinase B. Cancer Res 1999; 59: 1449–53.
- 37, , , , , , , , , , , , et al. Cyclin D1b protein expression in breast cancer is independent of cyclin D1a and associated with poor disease outcome. Oncogene 2009; 28: 1812–20.
- 38, , , , , , , , , , , , et al. Prediction of local recurrence, distant metastases and death following breast-conserving therapy in early-stage invasive breast cancer using a five biomarker panel. J Clin Oncol 2009; 27:(in press).
- 39, , , , , , , , , . Activation of PI3K/Akt signaling and hormone resistance in breast cancer. Breast Cancer 2006; 13: 137–44.
- 40, , , , , , , , , , . Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature 2008; 454: 776–9.
- 41, , , , , , , , . PTEN-deficient cancers depend on PIK3CB. Proc Natl Acad Sci USA 2008; 105: 13057–62.
- 42, . PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008; 27: 5497–510.
- 43, . Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression. Cell Cycle 2003; 2: 339–45.
- 44, , , , , . Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem 2001; 276: 9817–24.
- 45, , , , , , , , , , , . The association between Akt activation and resistance to hormone therapy in metastatic breast cancer. Eur J Cancer 2006; 42: 629–35.
- 46, , , , , , , , , , , , et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell 2007; 12: 395–402.
- 47, , , , , , , , , , , , et al. ERBB2 phosphorylation and trastuzumab sensitivity of breast cancer cell lines. Oncogene 2007; 26: 7163–9.
- 48, , , , , , . Phosphatase and tensin homologue deleted on chromosome 10 deficiency accelerates tumor induction in a mouse model of ErbB-2 mammary tumorigenesis. Cancer Res 2008; 68: 2122–31.
- 49, , , , , , , , , , , , et al. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet 2008; 40: 102–7.
- 50, , , , , , , , , , , , et al. The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer. Cancer Res 2004; 64: 830–5.
- 51, , , . The combination of high cyclin E and Skp2 expression in breast cancer is associated with a poor prognosis and the basal phenotype. Hum Pathol 2008; 39: 1431–7.
- 52, , , , , , , , , , , , et al. Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells. Breast. Cancer Res 2008; 10: R101.

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