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Molecular Markers of Risk of Subsequent Invasive Breast Cancer in Women with Ductal Carcinoma in Situ

Ductal carcinoma in situ (DCIS) is considered to be a non-obligate precursor of invasive breast cancer (IBC). Novel prognostic (and ultimately predictive) markers of IBC risk may emerge from assessment of expression patterns on a global scale. Our overarching goal in this study was to facilitate early detection of patients with DCIS at risk of IBC development. To this end, we conducted a nested case-control study using clinical data and archived formalin-fixed paraffin-embedded (FFPE) tissue from a large multi-center cohort of 8175 patients initially diagnosed with DCIS in community-based hospitals and health plans and followed for subsequent IBC development. Specifically, within this cohort, we observed that p16, COX-2, and MKI67 protein expression was not associated with altered risk of ipsilateral IBC. However, we did identify miRNA expression differences associated with risk of progression to subsequent IBC. Studies of this nature have the potential to lead to approaches that will help to refine identification of women with DCIS who need enhanced surveillance and early aggressive treatment.