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- W2023059920 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCINTRODUCTION: Activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway via kinase mutations or loss of PTEN is frequently reported in invasive breast cancer and laboratory models suggest that these “second hits” promote invasiveness in HER2 amplified disease. The role of PI3K pathway activation in the transition from in situ to invasive disease remains uncertain. The aim of this study was to assess the frequency of activating lesions in the PI3K pathway in pure high grade DCIS and DCIS associated with HER2 amplified invasive cancer.METHODS: 89 cases of pure high grade DCIS and 73 cases of DCIS associated with HER2 amplified (HER2+) invasive cancer were identified. Sections from FFPE blocks were used for IHC, FISH and DNA extraction. Pure DCIS, DCIS adjacent to invasive and matched invasive cancers were microdissected for multiplex array (Sequenom®) genotyping of PIK3CA and AKT. IHC was performed for HER2 and PTEN. HER2+ was confirmed by FISH. PTEN was scored relative to adjacent normal cells (scale 0-2).RESULTS: Among 89 cases of pure high grade DCIS, 51 (57%) were HER2+. PIK3CA mutations were identified in 13/73 (18%) HER2+ invasive lesions and in 11/13 cases the mutation was also present in the adjacent DCIS (11/73 (15%)). PIK3CA mutations were less common in pure HER2+ DCIS (2/51 (4%)) and pure HER2 neg DCIS (2/38 (5%)). Mutations in AKT1 were not identified HER2+ invasive lesions or the adjacent DCIS, yet were found in 3 cases of pure DCIS (2 HER2 neg, 1 HER2 +). PTEN loss was rare in HER2+ invasive lesions (4%), adjacent HER2+ DCIS (5%) and pure HER2+ DCIS (4%) but was seen in 7/38 (18%) cases of pure HER2 neg DCIS. Concomitant loss of PTEN and PIK3CA mutation was seen in 1 case of pure HER2 neg DCIS.CONCLUSIONS: PIK3CA mutations were observed with similar frequency in HER2+ invasive cancers and in the adjacent DCIS and were uncommon in pure DCIS, suggesting that mutational activation of PI3K may cooperate with HER2 in disease progression. PTEN loss was more common in HER2 neg DCIS and may not be mutually exclusive with PIK3CA mutations, suggesting that these mechanisms may interact in the progression of HER2 neg disease. AKT1 mutations were rare in pure DCIS and not identified in matched HER2+ DCIS and invasive cancer. These data support a role for activation of the PI3K pathway in the transition from in situ to invasive disease and suggest that the mechanism of activation may vary by HER2 status. Further work in HER2 neg DCIS and matched HER2 neg invasive cancer is underway.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5275." @default.
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- W2023059920 date "2010-04-15" @default.
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- W2023059920 title "Abstract 5275: Alternate mechanisms of PI3K pathway activation among subtypes of ductal carcinoma in situ suggest distinct pathways for progression to invasive disease" @default.
- W2023059920 doi "https://doi.org/10.1158/1538-7445.am10-5275" @default.
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