Breast cancer pathway (WP4262)
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.
Authors
Kristina Hanspers , Egon Willighagen , Irene Hemel , Friederike Ehrhart , and Eric WeitzActivity
Discuss this pathway
Check for ongoing discussions or start your own.
Cited In
- Shared Genetic Risk Factors Between Cancer and Cardiovascular Diseases (2022).
- Understanding signaling and metabolic paths using semantified and harmonized information about biological interactions (2022).
- Shared mechanisms and crosstalk of COVID-19 and osteoporosis via vitamin D (2022).
- Non-dialyzable uremic toxins and renal tubular cell damage in CKD patients: a systems biology approach (2024).
- Methylation analysis by targeted bisulfite sequencing in large for gestational age (LGA) newborns: the LARGAN cohort (2024).
Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.
Organisms
Homo sapiensCommunities
CPTAC DiseasesAnnotations
Disease Ontology
cancerPathway Ontology
phosphatidylinositol 3-kinase-Akt signaling pathway cancer pathway Notch signaling pathway disease pathway breast cancer pathwayReferences
- Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Science. 1987 Jan 9;235(4785):177–82. PubMed Europe PMC Scholia
- PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma. Saal LH, Holm K, Maurer M, Memeo L, Su T, Wang X, et al. Cancer Res. 2005 Apr 1;65(7):2554–9. PubMed Europe PMC Scholia
- FGFR1 amplification in breast carcinomas: a chromogenic in situ hybridisation analysis. Elbauomy Elsheikh S, Green AR, Lambros MBK, Turner NC, Grainge MJ, Powe D, et al. Breast Cancer Res. 2007;9(2):R23. PubMed Europe PMC Scholia
- An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, et al. Cancer Res. 2008 Aug 1;68(15):6084–91. PubMed Europe PMC Scholia
- Predictive biomarkers of sensitivity to the phosphatidylinositol 3’ kinase inhibitor GDC-0941 in breast cancer preclinical models. O’Brien C, Wallin JJ, Sampath D, GuhaThakurta D, Savage H, Punnoose EA, et al. Clin Cancer Res. 2010 Jul 15;16(14):3670–83. PubMed Europe PMC Scholia
- Potential for targeting the fibroblast growth factor receptors in breast cancer. Hynes NE, Dey JH. Cancer Res. 2010 Jul 1;70(13):5199–202. PubMed Europe PMC Scholia
- Activating HER2 mutations in HER2 gene amplification negative breast cancer. Bose R, Kavuri SM, Searleman AC, Shen W, Shen D, Koboldt DC, et al. Cancer Discov. 2013 Feb;3(2):224–37. PubMed Europe PMC Scholia
- PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia
- PI3K mutations in breast cancer: prognostic and therapeutic implications. Mukohara T. Breast Cancer (Dove Med Press). 2015 May 15;7:111–23. PubMed Europe PMC Scholia
- Proteogenomics connects somatic mutations to signalling in breast cancer. Mertins P, Mani DR, Ruggles KV, Gillette MA, Clauser KR, Wang P, et al. Nature. 2016 Jun 2;534(7605):55–62. PubMed Europe PMC Scholia
- Proteogenomic integration reveals therapeutic targets in breast cancer xenografts. Huang KL, Li S, Mertins P, Cao S, Gunawardena HP, Ruggles KV, et al. Nat Commun. 2017 Mar 28;8:14864. PubMed Europe PMC Scholia