Is there a role for molecular prognostic factors in the clinical management of ductal carcinoma in situ (DCIS) of the breast?

Abstract

The incidence of ductal carcinoma of the breast (DCIS) increased in Europe and the US up to 10-fold over the last 20 years ¿8. This could be linked to more vigorous screening mammography, as well as changes of histopathologic and diagnostic criteria for breast lesions during the last decades ¿31,26. Optimal screening for DCIS, the diagnostic procedures and best treatment is still controversial. For many DCIS patients lumpectomy and adjuvant radiotherapy are a valid treatment option. There is need for better prognostic factors in DCIS, which indicate the need for therapy and tailor the intensity of treatment. Recently prognostic factors based on clinical and pathological findings for DCIS were established and are currently validated. Molecular mechanisms involved in DCIS formation, DCIS progression to invasive breast cancer, and predicting DCIS treatment response are rapidly emerging ¿46. Here we discuss some of the known molecular mechanisms of DCIS and how they could be further exploited as prognostic factors for screening and tailoring DCIS therapy. This review will summarize relevant molecular mechanism of DCIS carcinogenesis including dysregulation of the cell cycle clock and changes of the apoptotic threshold. In particular, recently published molecular and cellular abnormalities in DCIS, potentially relevant for treatment decision, will be discussed.