Preneoplastic Low-Risk Mammary Ductal Lesions (Atypical Ductal Hyperplasia and Ductal Carcinoma In Situ Spectrum): Current Status and Future Directions

SIMPLE SUMMARY: Overtreatment which means providing a patient with unnecessary medical intervention has recently become the center of attention in breast diseases. One of these lesions is low-risk ductal carcinoma in situ (DCIS), for which the standard of treatment is wide local excision/mastectomy, with or without radiation therapy, with or without hormonal therapy. There are many worldwide ongoing clinical trials aiming to de-escalate this therapy by examining whether active surveillance (AS) is sufficient. These trials vary in pathology inclusion and exclusion criteria. There is lack of consensus on the definition of low-risk DCIS, in particular the overlap with atypical ductal hyperplasia (ADH), DCIS grading, and lack of definition of comedonecrosis. This review discusses AS trial from pathology standpoint and provides few recommendations. ABSTRACT: Intraepithelial mammary ductal neoplasia is a spectrum of disease that varies from atypical ductal hyperplasia (ADH), low-grade (LG), intermediate-grade (IG), to high-grade (HG) ductal carcinoma in situ (DCIS). While ADH has the lowest prognostic significance, HG-DCIS carries the highest risk. Due to widely used screening mammography, the number of intraepithelial mammary ductal neoplastic lesions has increased. The consequence of this practice is the increase in the number of patients who are overdiagnosed and, therefore, overtreated. The active surveillance (AS) trials are initiated to separate lesions that require active treatment from those that can be safely monitored and only be treated when they develop a change in the clinical/radiologic characteristics. At the same time, the natural history of these lesions can be evaluated. This review aims to evaluate ADH/DCIS as a spectrum of intraductal neoplastic disease (risk and histomorphology); examine the controversies of distinguishing ADH vs. DCIS and the grading of DCIS; review the upgrading for both ADH and DCIS with emphasis on the variation of methods of detection and the definitions of upgrading; and evaluate the impact of all these variables on the AS trials.