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The major drivers of breast cancer pathogenesis are hormone receptor-related genes, HER2 cluster of genes, and proliferation-associated genes. Based on the similarities of gene expression profiles using a hierarchical clustering, breast cancer has been subdivided into luminal A, luminal B, HER2-enriched, and basal-like subtypes.

These groupings have prognostic implications. Broadly speaking, luminal subtypes show expression of estrogen receptor (ER)-related genes and have better prognosis than HER2-enriched and basal-like subtypes, which are usually ER negative.

Luminal B Subtype: They are less common than Luminal A (about 20% of all breast cancers) and have comparatively worse prognosis. As compared to luminal A, they have higher Nottingham grade (as seen here), show lower expression levels of ER-related genes, variable expression of HER2 cluster (may be HER2 positive), and higher expression levels of proliferation-related genes.

Luminal B cancers are also quite heterogenous in the mutations they carry. The most frequently mutated genes include TP53 and PIK3CA. In addition, the site of abnormality in TP53 pathway appears to be different in luminal A and luminal B cancers. Luminal B cancers are a subset of ER-positive cancers that may benefit from more aggressive therapy.

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