ABSTRACT
In the assessment of breast cancer histopathological risk indicators, premalignant lesions are by no means trivial. A multitude of proliferative hyperplastic and premalignant alterations have been identifi ed, not uncommonly occurring synchronously with invasive carcinomas. Observational and correlative studies have identifi ed some of these lesions as risk indicators or premalignant with potential to progress to an overtly malignant phenotype (i.e., non-obligate breast cancer precursors) (1-4). Molecular studies have demonstrated that most of these risk indicators are clonal, neoplastic proliferations which have histological, immunohistochemical, and molecular features identical to those of matched invasive breast cancers (either synchronous or metachronous). Lesions that fulfi ll these criteria are therefore considered breast cancer precursors. As the chance of one of these precursors progressing to invasive breast cancer rarely equates to 100%, these lesions are more accurately described as non-obligate precursors (5). Current evidence indicates that epithelial proliferative diseases, including usual-type and atypical ductal epithelial hyperplasia, lobular neoplasia, and columnar cell lesions confer an increased risk of developing breast cancer. These lesions may be discovered coincidentally in the histopathology breast screening practice and they are associated with an increased risk of breast cancer in the same breast (ipsilateral) and to a lesser degree in the contralateral breast. There is a minimally increased risk of cancer in patients with usual-type epithelial hyperplasia which is associated with a 1.5-2.0 times risk of breast cancer during the subsequent 10-15 years after diagnosis. Atypical ductal hyperplasia (ADH) is associated with a 4.6-fold increased risk, although this risk falls after 10-15 years toward that of a control population (6). However, if there is an associated family history (at least one fi rst-degree relative), the risk associated with ADH doubles (7). Atypical lobular hyperplasia confers a four-to fi vefold-increased relative risk, and
lobular carcinoma in situ an 8-to 10-fold increased risk (8). The presence of pure columnar cell lesions alone is associated with a mild increase in the overall breast cancer risk (risk ratio 1.47) (9,10).
