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.

Ductal carcinoma in situ diagnosed by breast needle biopsy: Predictors of invasion in the excision specimen.

BACKGROUND: A substantial proportion of women with a pre-operative diagnosis of pure ductal carcinoma in situ (DCIS) has a final diagnosis of invasive breast cancer (IBC) after surgical excision and, consequently, a potential indication for lymph node staging. The aim of our study was to identify novel predictors of invasion in patients with a needle-biopsy diagnosis of DCIS that would help us to select patients that may benefit from a sentinel node biopsy (SNB). PATIENTS AND METHODS: We included 153 patients with a needle-biopsy diagnosis of DCIS between 2000 and 2014, which was followed by surgical excision. Several pre-operative clinical, radiological and pathological features were assessed and correlated with the presence of invasion in the excision specimen. Features that were significantly associated with upstaging in the univariable analysis were combined to calculate upstaging risks. RESULTS: Overall, 22% (34/155) of the patients were upstaged to IBC. The following risk factors were significantly associated with upstaging: palpability, age ≤40 years, mammographic mass lesion, moderate to severe periductal inflammation and periductal loss of decorin expression. The upstaging-risk correlated with the number of risk factors present: e.g. 9% for patients without risk factors, 29% for patients with 1 risk factor, 37% for patients with 2 risk factors and 54% for patients with ≥3 risk factors. CONCLUSION: The identified risk factors may be helpful to predict the upstaging-risk for patients with a needle-biopsy diagnosis of pure DCIS, which facilitates the performance of a selective SNB for high-risk patients and avoid this procedure in low-risk patients.