[Ductal and lobular preneoplasia: role in breast cancer development]

With the widespread use of screening mammography and core needle biopsies, preneoplastic lesions of the breast are observed with increasing frequency. Unlike low-grade ductal carcinoma in situ (lg-DCIS), a possible precursor role of atypical ductal hyperplasia (ADH), lobular neoplasia (LN), and flat epithelial atypia (FEA) as well as their risk of progression have not been clearly defined. The aim of the present study was to evaluate the biological potential of these early low-grade lesions in the development of breast cancer.

Different series of precursor lesions and syn- or metachronous invasive carcinomas were tested for clonality using mitochondrial DNA sequencing, analysis of E-cadherin inactivation and comparative allelotyping with a panel of 14 polymorphous STR markers.

In a series of invasive carcinomas occurring up to 10 years after the initial diagnosis of lobular neoplasia, a direct (clonal) association was established between LN and 3 of 5 invasive lobular cancers (ILC) but not in any of the cases with ductal secondary tumors. Tests on lg-DCIS and FEA occurring in association with tubular breast carcinomas demonstrated a direct clonal relationship in 67 and 70% of cases, respectively, and comparative allelotyping revealed a high degree of homology in the patterns of chromosomal imbalances. In addition, FEA and lg-DCIS, but not LN, were frequently closely related with each other.

The present data provide molecular evidence for a direct clonal relationship of LN and ILC as well as of FEA and lg-DCIS with tubular breast carcinomas. However, the multifocal occurrence and frequent coexistence of the different precursor lesions suggests the presence of (possibly hormone-induced) field effects on the breast parenchyma.