Abstract
Human breast cancers referred to as “basal-like” are of interest because they lack effective therapies and their biology is poorly understood. The term basal-like derives from studies demonstrating tumor gene expression profiles that include some transcripts characteristic of the basal cells of the normal adult human mammary gland and others associated with a subset of normal luminal cells. Elucidating the mechanisms responsible for the profiles of basal-like tumors is an active area of investigation. More refined molecular analysis of patients' samples and genetic strategies to produce breast cancers de novo from defined populations of normal mouse mammary cells have served as complementary approaches to identify relevant pathway alterations. However, both also have limitations. Here, we review some of the underlying reasons, including the unifying concept that some normal luminal cells have both luminal and basal features, as well as some emerging new avenues of investigation.
Highlights
Remarkable technical advances are improving our understanding of normal human breast biology and the identification of perturbed pathways and mutations implicated in their transformation
Basal-like The term ‘‘basal-like’’ was introduced in 2001 (Sorlie et al, 2001) to refer to a group of human breast cancers that share an RNA signature that includes a high expression of cytokeratins 5 and 17 (CK5 and CK17), laminin, and fatty acid binding protein 7; i.e., proteins found in basal cells but not luminal cells of the normal human mammary gland
Adenomyoepithelial tumors produced in mice have a very well-defined myoepithelial layer, with features suggesting they are at the benign end of the spectrum with either the presence or absence of SMA in the basal layer
Summary
Human breast cancers referred to as ‘‘basal-like’’ are of interest because they lack effective therapies and their biology is poorly understood. The term basal-like derives from studies demonstrating tumor gene expression profiles that include some transcripts characteristic of the basal cells of the normal adult human mammary gland and others associated with a subset of normal luminal cells. Elucidating the mechanisms responsible for the profiles of basal-like tumors is an active area of investigation. More refined molecular analysis of patients’ samples and genetic strategies to produce breast cancers de novo from defined populations of normal mouse mammary cells have served as complementary approaches to identify relevant pathway alterations. We review some of the underlying reasons, including the unifying concept that some normal luminal cells have both luminal and basal features, as well as some emerging new avenues of investigation
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