WP4262 - Breast cancer pathway - Homo sapiens

Breast cancer is the leading cause of cancer death among women worldwide. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland.

The molecular subtypes of breast cancer, which are based on the presence or absence of hormone receptors (estrogen and progesterone subtypes) and human epidermal growth factor receptor-2 (HER2), include:

* Luminal A subtype: Hormone receptor positive (progesterone and estrogen) and HER2 (ERBB2) negative

* Luminal B subtype: Hormone receptor positive (progesterone and estrogen) and HER2 (ERBB2) positive

* HER2 positive: Hormone receptor negative (progesterone and estrogen) and HER2 (ERBB2) positive

* Basal-like or triple-negative (TNBCs): Hormone receptor negative (progesterone and estrogen) and HER2 (ERBB2) negative

Hormone receptor positive breast cancers are largely driven by the estrogen/ER pathway. In HER2 positive breast tumors, HER2 activates the PI3K/AKT and the RAS/RAF/MAPK pathways, and stimulate cell growth, survival and differentiation. In patients suffering from TNBC, the deregulation of various signaling pathways (Notch and Wnt/beta-catenin), EGFR protein have been confirmed. In the case of breast cancer only 8% of all cancers are hereditary, a phenomenon linked to genetic changes in BRCA1 or BRCA2. Somatic mutations in only three genes (TP53, PIK3CA and GATA3) occurred at >10% incidence across all breast cancers. Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.