Benign proliferative epithelial disorders of the breast: a review of the epidemiologic evidence

Abstract

Benign breast disease (BBD) is a heterogeneous condition consisting of many histological entities [1], including ductal epithelial proliferations, adenomas and papillomas, and fibroadenomas [2]. Some of these lesions are thought to represent progressive changes in the stepwise sequence of histological changes leading to the development of breast cancer. Specifically, it has been hypothesized that non-atypical proliferative forms of BBD, proliferative disease with atypia, and in situ cancer represent successive steps preceding the development of invasive breast carcinoma [3]. This hypothesis is supported by experimental and epidemiologic evidence. Experimentally, xenografts of MCF10AneoT cells have been shown to progress from intraductal proliferative changes to lesions resembling atypical hyperplasia of the human breast and ultimately to lesions resembling carcinoma in situ [4]; this step-wise development of breast cancer has also been demonstrated using transgenic rat [5] andmouse [6] models. Epidemiologic studies have shown that women with proliferative epithelial disorders affecting the small ducts and the terminal ductal lobular units of the breast are at increased risk of subsequent breast cancer, particularly when the epithelial proliferation is accompanied by evidence of atypia [1, 7–9]. Risk is increased approximately 1.5–2 fold for those with epithelial proliferation without atypia [7–9] and 4–5 fold for those with proliferative disease with atypia [8, 10]. The higher risk associatedwith atypia is consistent with the notion that it ismore proximal to carcinoma thanproliferative disease without atypia. Given these findings, benign proliferative epithelial disorders (BPED) of the breast are considered to have malignant potential [11]. Our focus in the remainder of this review is on BPED of the breast.