Biological variables and prognosis of DCIS.

Based on current knowledge, biological factors that have been investigated in ductal carcinoma in situ (DCIS) include histology of these lesions, the impact of margin status on local recurrence, and several genetic alterations. Optimal integration of these factors in guiding optimal therapy is of great importance, since the incidence of DCIS is rising as a result of population-based mammographic screening. Mastectomy will almost always cure patients with DCIS but represents overtreatment for many. Less extensive treatment options should combine an optimal cosmetic result with the same safety for outcome of disease as mastectomy. To guide such optimal treatment, histological classification is not sufficient and additional biological factors are being investigated for their ability to predict outcome for individual patients with DCIS. In this review, the histological classification of DCIS is described and in addition the emerging knowledge on genetic alterations is summarised. For clinical management of DCIS patients, genetic or other biological factors should be identified that can predict the risk of progression of DCIS to invasive breast cancer and distant metastases. At present, insufficient knowledge on prognostic and predictive factors in DCIS is available. Research in this area is hampered by the difficulties in obtaining DCIS tumour tissue, as the tumour cells grow in the lumen of pre-existing ducts and lobules. As the recurrence rates are relatively low and the most relevant clinical endpoint, distant metastases, is indeed very rare, large numbers of patients (hundreds to a few thousand) need to be studied. Integration of translational studies into clinical trials aimed at optimising the treatment of DCIS are required to achieve this goal.