Progression of ductal carcinoma in situ to invasive breast cancer: comparative genomic sequencing.

Several models have been described as potential mechanisms for the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC). The aim of our study was to increase our understanding of DCIS progression by using massive parallel sequencing of synchronous DCIS and IBC. We included patients with synchronous DCIS and IBC (n = 4). Initially, IBC and normal tissue were subjected to whole exome sequencing. Subsequently, targeted sequencing was performed to validate those tumor-specific variants identified by whole exome sequencing. Finally, we analyzed whether those specific variants of the invasive component were also present in the DCIS component. There was a high genomic concordance between synchronous DCIS and IBC (52 out of 92 mutations were present in both components). However, the remaining mutations (40 out of 92) were restricted to the invasive component. The proportion of tumor cells with these mutations was higher in the invasive component compared to the DCIS component in a subset of patients. Our findings support the theory that the progression from DCIS to IBC could be driven by the selection of subclones with specific genetic aberrations. This knowledge improves our understanding of DCIS progression, which may lead to the identification of potential markers of progression and novel therapeutic targets in order to develop a more personalized treatment of patients with DCIS.

Polytetrafluoroethylene covered stent placement for focal occlusive disease of the infrarenal aorta.

BACKGROUND: Arterial insufficiency is rarely caused by isolated infrarenal aortic occlusive lesions. Endovascular treatment options include plain balloon angioplasty and bare metal stent placement. In this study the feasibility and efficacy of polytetrafluoroethylene (PTFE) covered balloon expandable stents were evaluated. MATERIAL AND METHODS: Consecutive patients from two centers were prospectively collected in a database and retrospectively analyzed. Results were evaluated by clinical examination, ankle-brachial indices (ABI), duplex ultrasound, and plain abdominal radiography. RESULTS: Thirty-six consecutive patients were treated between November 2008 and June 2013. Indication for treatment was Rutherford 3 (n = 29), 4 (n = 3), and 5 (n = 4). Technical success was always achieved and there were no distal embolizations or vessel wall ruptures. The median follow-up was 22 months (range 0-60). All patients improved clinically and the ABI increased significantly from 0.73 ± 0.18 to 1.01 ± 0.14 (p < .01). One patent covered stent was removed surgically because of infection. Primary patency rates were 100% at 1 and 2 years without stent fractures. CONCLUSION: The use of PTFE covered stents for the treatment of isolated infrarenal aortic occlusive disease is safe and very effective. Patency rates are excellent and complications including distal embolization and vessel wall rupture are extremely rare.