KEGG   PATHWAY: hsa05224
hsa05224                    Pathway                                
Breast cancer - Homo sapiens (human)
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: hormone receptor positive and HER2 negative (luminal A subtype), hormone receptor positive and HER2 positive (luminal B subtype), hormone receptor negative and HER2 positive (HER2 positive), and hormone receptor negative and HER2 negative (basal-like or triple-negative breast cancers (TNBCs)). Hormone receptor positive breast cancers are largely driven by the estrogen/ER pathway. In HER2 positive breast tumours, 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 signalling 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.
Human Diseases; Cancer: specific types
Pathway map
hsa05224  Breast cancer

nt06210  ERK signaling
nt06214  PI3K signaling
nt06215  WNT signaling
nt06216  NOTCH signaling
nt06227  Nuclear receptor signaling
nt06230  Cell cycle
nt06240  Transcription
nt06260  Colorectal cancer
nt06261  Gastric cancer
nt06262  Pancreatic cancer
nt06263  Hepatocellular carcinoma
nt06265  Bladder cancer
nt06266  Non-small cell lung cancer
nt06267  Small cell lung cancer
nt06268  Melanoma
nt06269  Basal cell carcinoma
nt06270  Breast cancer
nt06271  Endometrial cancer
nt06272  Prostate cancer
nt06273  Glioma
nt06274  Thyroid cancer
nt06276  Chronic myeloid leukemia
N00020  Amplified FGFR to RAS-ERK signaling pathway
N00022  ERBB2-overexpression to RAS-ERK signaling pathway
N00034  ERBB2-overexpression to PI3K signaling pathway
N00038  Amplified FGFR to PI3K signaling pathway
N00041  EGFR-overexpression to RAS-ERK signaling pathway
N00042  EGFR-overexpression to PI3K signaling pathway
N00049  Mutation-activated PI3K to PI3K signaling pathway
N00050  Amplified PI3K to PI3K signaling pathway
N00052  Mutation-inactivated PTEN to PI3K signaling pathway
N00059  FZD7-overexpression to Wnt signaling pathway
N00060  LRP6-overexpression to Wnt signaling pathway
N00087  NOTCH-overexpression to Notch signaling pathway
N00115  Mutation-inactivated TP53 to transcription
N00275  Amplified CCND1 to cell cycle G1/S
N00287  ESR1-positive to nuclear-initiated estrogen signaling pathway
H00031  Breast cancer
D00554  Ethinyl estradiol (USP)
D00951  Medroxyprogesterone acetate (JP18/USP)
D00966  Tamoxifen citrate (JP18/USP)
D00967  Toremifene citrate (JAN/USAN)
D01161  Fulvestrant (JAN/USP/INN)
D01602  Mepitiostane (JP18/INN)
D02714  Everolimus (JAN/USAN/INN)
D03257  Trastuzumab (USAN/INN)
D04024  Lapatinib ditosylate (USAN)
D05446  Pertuzumab (USAN/INN)
D08108  Lapatinib (INN)
D08950  Neratinib (USAN/INN)
D09980  Trastuzumab emtansine (USAN/INN)
D10372  Palbociclib (JAN/USAN)
D10446  Margetuximab (USAN/INN)
D10688  Abemaciclib (JAN/USAN/INN)
D10898  Neratinib maleate
D10979  Ribociclib succinate (USAN)
D11011  Alpelisib (JAN/USAN/INN)
D11141  Tucatinib (USAN/INN)
D11671  Elacestrant (USAN/INN)
D11672  Elacestrant hydrochloride (USAN)
D11829  Fluoroestradiol F18
D12442  Tucatinib ethanolate (JAN)
Homo sapiens (human) [GN:hsa]
2099  ESR1; estrogen receptor 1 [KO:K08550]
2100  ESR2; estrogen receptor 2 [KO:K08551]
8648  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:]
8202  NCOA3; nuclear receptor coactivator 3 [KO:K11256] [EC:]
2353  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
6667  SP1; Sp1 transcription factor [KO:K04684]
595  CCND1; cyclin D1 [KO:K04503]
4609  MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377]
5241  PGR; progesterone receptor [KO:K08556]
7471  WNT1; Wnt family member 1 [KO:K03209]
54361  WNT4; Wnt family member 4 [KO:K00408]
8600  TNFSF11; TNF superfamily member 11 [KO:K05473]
2064  ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:]
2246  FGF1; fibroblast growth factor 1 [KO:K18496]
2247  FGF2; fibroblast growth factor 2 [KO:K18497]
2248  FGF3; fibroblast growth factor 3 [KO:K04358]
2249  FGF4; fibroblast growth factor 4 [KO:K04358]
8822  FGF17; fibroblast growth factor 17 [KO:K04358]
2251  FGF6; fibroblast growth factor 6 [KO:K04358]
2252  FGF7; fibroblast growth factor 7 [KO:K04358]
2253  FGF8; fibroblast growth factor 8 [KO:K04358]
2254  FGF9; fibroblast growth factor 9 [KO:K04358]
2255  FGF10; fibroblast growth factor 10 [KO:K04358]
8823  FGF16; fibroblast growth factor 16 [KO:K04358]
2250  FGF5; fibroblast growth factor 5 [KO:K04358]
8817  FGF18; fibroblast growth factor 18 [KO:K04358]
26281  FGF20; fibroblast growth factor 20 [KO:K04358]
27006  FGF22; fibroblast growth factor 22 [KO:K04358]
9965  FGF19; fibroblast growth factor 19 [KO:K22603]
26291  FGF21; fibroblast growth factor 21 [KO:K22429]
8074  FGF23; fibroblast growth factor 23 [KO:K22428]
2260  FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:]
3479  IGF1; insulin like growth factor 1 [KO:K05459]
3480  IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:]
1950  EGF; epidermal growth factor [KO:K04357]
1956  EGFR; epidermal growth factor receptor [KO:K04361] [EC:]
3815  KIT; KIT proto-oncogene, receptor tyrosine kinase [KO:K05091] [EC:]
6464  SHC1; SHC adaptor protein 1 [KO:K06279]
25759  SHC2; SHC adaptor protein 2 [KO:K17447]
53358  SHC3; SHC adaptor protein 3 [KO:K17448]
399694  SHC4; SHC adaptor protein 4 [KO:K17449]
2885  GRB2; growth factor receptor bound protein 2 [KO:K04364]
6654  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
369  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:]
673  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
5728  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
2475  MTOR; mechanistic target of rapamycin kinase [KO:K07203] [EC:]
6198  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:]
6199  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:]
182  JAG1; jagged canonical Notch ligand 1 [KO:K06052]
3714  JAG2; jagged canonical Notch ligand 2 [KO:K21635]
10683  DLL3; delta like canonical Notch ligand 3 [KO:K06051]
28514  DLL1; delta like canonical Notch ligand 1 [KO:K06051]
54567  DLL4; delta like canonical Notch ligand 4 [KO:K06051]
4851  NOTCH1; notch receptor 1 [KO:K02599]
4853  NOTCH2; notch receptor 2 [KO:K20994]
4854  NOTCH3; notch receptor 3 [KO:K20995]
4855  NOTCH4; notch receptor 4 [KO:K20996]
3280  HES1; hes family bHLH transcription factor 1 [KO:K06054]
388585  HES5; hes family bHLH transcription factor 5 [KO:K06055]
26508  HEYL; hes related family bHLH transcription factor with YRPW motif like [KO:K09091]
23462  HEY1; hes related family bHLH transcription factor with YRPW motif 1 [KO:K09091]
23493  HEY2; hes related family bHLH transcription factor with YRPW motif 2 [KO:K09091]
2324  FLT4; fms related receptor tyrosine kinase 4 [KO:K05097] [EC:]
1026  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
4791  NFKB2; nuclear factor kappa B subunit 2 [KO:K04469]
7472  WNT2; Wnt family member 2 [KO:K00182]
7482  WNT2B; Wnt family member 2B [KO:K00182]
7473  WNT3; Wnt family member 3 [KO:K00312]
89780  WNT3A; Wnt family member 3A [KO:K00312]
7474  WNT5A; Wnt family member 5A [KO:K00444]
81029  WNT5B; Wnt family member 5B [KO:K00444]
7475  WNT6; Wnt family member 6 [KO:K00445]
7476  WNT7A; Wnt family member 7A [KO:K00572]
7477  WNT7B; Wnt family member 7B [KO:K00572]
7478  WNT8A; Wnt family member 8A [KO:K00714]
7479  WNT8B; Wnt family member 8B [KO:K00714]
7483  WNT9A; Wnt family member 9A [KO:K01064]
7484  WNT9B; Wnt family member 9B [KO:K01064]
7480  WNT10B; Wnt family member 10B [KO:K01357]
80326  WNT10A; Wnt family member 10A [KO:K01357]
7481  WNT11; Wnt family member 11 [KO:K01384]
51384  WNT16; Wnt family member 16 [KO:K01558]
8321  FZD1; frizzled class receptor 1 [KO:K02432]
8324  FZD7; frizzled class receptor 7 [KO:K02432]
2535  FZD2; frizzled class receptor 2 [KO:K02235]
7976  FZD3; frizzled class receptor 3 [KO:K02329]
8322  FZD4; frizzled class receptor 4 [KO:K02354]
7855  FZD5; frizzled class receptor 5 [KO:K02375]
8325  FZD8; frizzled class receptor 8 [KO:K02375]
8323  FZD6; frizzled class receptor 6 [KO:K02376]
11211  FZD10; frizzled class receptor 10 [KO:K02842]
8326  FZD9; frizzled class receptor 9 [KO:K02842]
4041  LRP5; LDL receptor related protein 5 [KO:K03068]
4040  LRP6; LDL receptor related protein 6 [KO:K03068]
1857  DVL3; dishevelled segment polarity protein 3 [KO:K02353]
1856  DVL2; dishevelled segment polarity protein 2 [KO:K02353]
1855  DVL1; dishevelled segment polarity protein 1 [KO:K02353]
10023  FRAT1; FRAT regulator of WNT signaling pathway 1 [KO:K03069]
23401  FRAT2; FRAT regulator of WNT signaling pathway 2 [KO:K03096]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
8312  AXIN1; axin 1 [KO:K02157]
8313  AXIN2; axin 2 [KO:K04385]
324  APC; APC regulator of WNT signaling pathway [KO:K02085]
10297  APC2; APC regulator of WNT signaling pathway 2 [KO:K02085]
1499  CTNNB1; catenin beta 1 [KO:K02105]
122011  CSNK1A1L; casein kinase 1 alpha 1 like [KO:K08957] [EC:]
1452  CSNK1A1; casein kinase 1 alpha 1 [KO:K08957] [EC:]
6932  TCF7; transcription factor 7 [KO:K02620]
83439  TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
7157  TP53; tumor protein p53 [KO:K04451]
1647  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
4616  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
10912  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
578  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
1643  DDB2; damage specific DNA binding protein 2 [KO:K10140]
51426  POLK; DNA polymerase kappa [KO:K03511] [EC:]
1019  CDK4; cyclin dependent kinase 4 [KO:K02089] [EC:]
1021  CDK6; cyclin dependent kinase 6 [KO:K02091] [EC:]
5925  RB1; RB transcriptional corepressor 1 [KO:K06618]
1869  E2F1; E2F transcription factor 1 [KO:K17454]
1870  E2F2; E2F transcription factor 2 [KO:K09389]
1871  E2F3; E2F transcription factor 3 [KO:K06620]
672  BRCA1; BRCA1 DNA repair associated [KO:K10605] [EC:]
675  BRCA2; BRCA2 DNA repair associated [KO:K08775]
C00410  Progesterone
C00951  Estradiol-17beta
C05981  Phosphatidylinositol-3,4,5-trisphosphate
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hsa03440  Homologous recombination
hsa04010  MAPK signaling pathway
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04310  Wnt signaling pathway
hsa04330  Notch signaling pathway
hsa04915  Estrogen signaling pathway
KO pathway

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