Multistep model of breast cancer progression Multistep model of breast cancer progression. There are two distinct pathways of progression: low- and high-grade pathways. The low-grade precursor lesions include usual-type ductal hyperplasia (UDH), columnar cell lesions (CCL), flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), well-differentiated ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS). The low-grade pathway typically gives rise to hormone receptor-positive, HER2-negative invasive mammary carcinomas (IMC) with a low proliferation rate. The early precursor lesions for most of invasive carcinomas in the high-grade pathway are unclear. Microglandular adenosis (MGA) and atypical apocrine hyperplasia (AAH) are likely candidates for some of these tumors. High-grade DCIS and pleomorphic LCIS may give rise to high-grade tumors. While diverse in their gene expression patterns, the high-grade tumors fall into three broad groups: (1) hormone receptor-positive, HER2-negative with high proliferation rate (luminal B), (2) triple-negative (basal like/claudin-low), and (3) HER2 positive. In general, invasive mammary carcinomas show tremendous biologic diversity including tumors that do not fit into the low- or high-grade pathway, showing intermediate-grade biology. Source: Breast Pathology, Pathology: A Modern Case Study Citation: Reisner HM. Pathology: A Modern Case Study; 2015 Available at: http://accessmedicine.mhmedical.com/DownloadImage.aspx?image=/data/books/1569/rei_ch16_f019.png&sec=95971285&BookID=1569&ChapterSecID=95971193&imagename= Accessed: October 10, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved