Molecular classification of breast carcinomas with particular emphasis on "basal-like" carcinoma: a critical review

During the last 11 years, 5 molecular subtypes of breast carcinoma (luminal A, luminal B, Her2-positive, basal-like, and normal breast-like) have been characterized and intensively studied. As genomic research evolves, further subtypes of breast cancers into new "molecular entities" are expected to occur. For example, a new and rare breast cancer subtype, known as claudin-low, has been recently found in human carcinomas and in breast cancer cell lines. There is no doubt that global gene expression analyses using high-throughput biotechnologies have drastically improved our understanding of breast cancer as a heterogeneous disease. The main question is, however, whether new molecular techniques such as gene expression profiling (or signature) should be regarded as the gold standard for identifying breast cancer subtypes. A critical review of the literature clearly shows major problems with current molecular techniques and classification including poor definitions, lack of reproducibility, and lack of quality control. Therefore, the current molecular approaches cannot be incorporated into routine clinical practice and treatment decision making as they are immature or even can be misleading. This review particularly focuses on the "basal-like" breast cancer subtype that represents one of the most popular breast cancer "entities". It critically shows major problems and misconceptions with and about this subtype and challenges the common claim that it represents a "distinct entity". It concludes that the term "basal-like" is misleading and states that there is no evidence that expression of basal-type cytokeratins in a given breast cancer, regardless of other established prognostic factors, does have any impact on clinical outcome.