Biological markers in DCIS and risk of breast recurrence: A systematic review

Understanding of the biology and clinical behavior of ductal carcinoma in situ (DCIS) is currently inadequate. The aim of this comprehensive review was to identify important molecular biological markers associated with DCIS and candidate markers associated with increased risk of ipsilateral recurrence after diagnosis of DCIS. A comprehensive systematic review was performed to identify studies published in the past 10 years that investigated biological markers in DCIS. To be included in this review, studies that investigated the rate of biological expression of markers had to report on at least 30 patients; studies that analyzed the recurrence risk associated with biomarker expression had to report on at least 50 patients. There were 6,252 patients altogether in our review. Biological markers evaluated included steroid receptors, proliferation markers, cell cycle regulation and apoptotic markers, angiogenesis-related proteins, epidermal growth factor receptor family receptors, extracellular matrix-related proteins, and COX-2. Although the studies in this review provide valuable preliminary information regarding the expression and prognostic significance of biomarkers in DCIS, common limitations of published studies (case-series, cohort, and case-control studies) were that they were limited to small patient cohorts in which the extent of surgery and use of radiotherapy or endocrine therapy varied from patient to patient, and variable methods of determining biomarker expression. These constraints made it difficult to interpret the absolute effect of expression of various biomarkers on risk of local recurrence. No prospective validation studies were identified. As the study of biomarkers are in their relative infancy in DCIS compared with invasive breast cancer, key significant prognostic and predictive markers associated with invasive breast cancer have not been adequately studied in DCIS. There is a critical need for prospective analyses of novel and other known breast cancer molecular markers in large cohorts of patient with DCIS to differentiate indolent from aggressive DCIS and better tailor the need and extent of current therapies.