Intermediate histological effect markers for breast cancer

The evidence that ductal carcinoma of the breast (DCIS) is an obligate precursor of invasive breast cancer and thus qualifies as an intermediate effect marker in chemoprevention research is reviewed. Much of the evidence on the natural history of DCIS has been derived from the era before the introduction of mammographic screening. Thus it may not be applicable in the present situation when women are likely to be under mammographic surveillance in chemoprevention trials. Further, the data that are becoming available from breast screening trials suggest that at least over follow-up periods now exceeding a decade, detection and treatment of DCIS has no impact on subsequent incidence of breast cancer. Although there are some indications that other biomarkers of malignancy are expressed similarly in DCIS and invasive cancer of similar grade, this evidence may not be sufficient to allow exclusive reliance on DCIS as an intermediate-effect marker in chemoprevention research.