Abstract P6-05-12: Comprehensive molecular analysis of estrogen receptor positive breast cancer to determine clinically actionable alterations
| Autor: | C Criscitello, Sherene Loi, Ling-Yuh Huw, Heidi Savage, M.J. Piccart, Lackner, Christos Sotiriou, Roberto Salgado, I Laios, Carol L. O'brien, L Pugliano, Stefan Michiels, Debora Fumagalli, Timothy R. Wilson |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cancer Research. 73:P6-05 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Introduction. Understanding the genetic landscape of estrogen receptor positive breast caner is critical for defining clinically actionable alleles that may be targeted using next generation biologics. PIK3CA mutations have previously been reported to be the most common mutation within estrogen receptor positive breast cancer, however the overlap and mutual exclusivity with other key driving alleles is poorly understood, especially how these biomarkers change following treatment failure. We custom designed a mutation, copy number variation and RNA expression panels to profile biomarkers from low quality formalin fixed paraffin embedded extracted material. Data relating to key pathways, such as PI3K and immune modulatory pathways, and overlap with other biomarkers will be presented. Methods. Formalin fixed paraffin embedded material was available from 195 primary cases and 95 paired metastatic estrogen receptor positive breast cancer patients. Samples were assayed for the expression of PTEN by IHC, hotspot mutations in 11 oncogenic driving genes using Q-PCR based technology, copy number alterations in 42 genes using Q-PCR based technology and RNA expression using a custom designed 400 breast cancer specific NanoString gene panel. Results. PTEN loss, as defined by H-score of 0, was found in 4.5% of primary samples and in 4.3% of metastatic samples. PIK3CA mutations were found in 43% of primary samples and in 38% of metastatic samples and were largely found to be mutually exclusive with PTEN loss. AKT1 mutations were found in 5.4% of primary samples and in 4.1% of metastatic samples. Less frequent mutations in KRAS (7.0%) and BRAF (1.7%) were found in the primary sample, and some were co-existing with PIK3CA mutations. Copy number gains were found in CCND1 (23.5%), ZNF703 (19.5%), FGFR1 (16.8%) and PAK1 (11.4%) and were largely concordant with the paired metastatic sample. Analysis with clinical outcome is ongoing. Conclusions. PIK3CA was the most frequently altered gene detected and was mutually exclusive with other key driving mutations within the PI3K pathway (AKT1 and PTEN). A strong concordance was observed between genetic alterations found in the primary sample and the paired metastatic sample. Mutations and expression gains within clinically actionable targets were found less frequently, but may provide alternative treatment strategies for these patients following failure of endocrine therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-12. |
| Databáze: | OpenAIRE |
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