Classification of breast cancer subtypes based on RNA profiling and immunohistochemical methods: clinical and biological aspects: A review

Transcriptome analysis provided a tool to identify expression subtypes of breast cancer (BC). A significant part of BCs are carcinomas that differ in the expression of luminal mammary ductal epithelium markers and estrogen signaling cascade genes (luminal subtypes A and B). Another group of BCs is characterized by the expression of ductal basal lining genes. Another subtype of BC has genes typically expressed in HER2-induced tumors. Immunohistochemical (IHC) examination is reliable in identifying the tumor subtype. Tumors with high IHC-expression of estrogen (ER) and progesterone (PR) receptors with no signs of HER2 gene activation and low proliferative activity should be referred to as luminal type A. The absence of ER, PR, and HER2 expression should be considered a sign of basal tumor subtype. However, the IHC classification cannot reliably distinguish HER2-positive tumors and HER2-enriched subtypes, which do not reflect the biological features of some BCs. For instance, a significant number of ER-positive breast cancer patients included in the MONALEESA ribociclib clinical study had HER2-subtype transcriptional signatures in the absence of HER2 receptor expression, and these were the ones who demonstrated a pronounced response to treatment.