miRNAs as Potential Predictive Biomarkers for ADH Diagnosed by CNB

Sidney Fu, M.D., Ph.D. and Rachel Brem, M.D., Investigators
December 18, 2013

The currently accepted stepwise model of breast tumorigenesis assumes a gradual transition from epithelial hyperproliferation (including ADH) to ductal carcinoma in situ(DCIS) and then to invasive ductal carcinoma (IDC). This progression model is strongly supported by clinical and epidemiological data and by molecular clonally studies. ADH is an abnormal proliferative lesion of the breast epithelium, which meets some but not all criteria of low grade DC IS.  ADH carries a 4-5 times increased risk of subsequent development of IDC in either breast. Genetic analysis of some ADH cells indicates that they may be associated with cancer, suggesting ADH may be a direct precursor of malignancy. Percutaneous core needle biopsy (CNB) is the standard technique for histological diagnosis of breast lesions, of which the findings are in agreement with surgical biopsy in more than 95% of the cases.

However, the CNB is less reliable for diagnosing ADH. There are variable reports in CNB diagnosis of ADH, with 11%-47% of cases to be DC IS or IDC on subsequent surgical excision. This is largely due to the difficulty in differentiating between ADH and low grade DCIS on the small amount of tissue obtained from core biopsy. Because foci of ADH may be present at the peripheral areas of DCIS, even a definitive diagnosis of ADH does not preclude the presence of more advanced lesions. Therefore, the standard of care for a diagnosis of ADH on CNB is surgical excision to exclude DCIS or IDC. Identification of patients with ADH diagnosed by CNB who may not need surgical excision is of clinical significance. However, none of the clinical, radiologic, and pathologic parameters are reliable in predicting the outcome of AD H. The aim of this pilot study is to identify miRNA biomarkers, along with other know factors to predict the outcome of ADH.