Entry
Name
Breast cancer - Homo sapiens (human)
Description
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.
Class
Human Diseases; Cancer: specific types
BRITE hierarchy
Pathway map
Ortholog table
Network
Element
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
Disease
Drug
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)
D04024 Lapatinib ditosylate (USAN)
D09980 Trastuzumab emtansine (USAN/INN)
D10446 Margetuximab (USAN/INN)
D10688 Abemaciclib (JAN/USAN/INN)
D10979 Ribociclib succinate (USAN)
D11011 Alpelisib (JAN/USAN/INN)
D11672 Elacestrant hydrochloride (USAN)
D12442 Tucatinib ethanolate (JAN)
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
2353 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
3725 JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448 ]
4609 MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377 ]
8600 TNFSF11; TNF superfamily member 11 [KO:K05473 ]
8822 FGF17; fibroblast growth factor 17 [KO:K04358 ]
2255 FGF10; fibroblast growth factor 10 [KO:K04358 ]
8823 FGF16; fibroblast growth factor 16 [KO:K04358 ]
8817 FGF18; fibroblast growth factor 18 [KO:K04358 ]
9965 FGF19; fibroblast growth factor 19 [KO:K22603 ]
8074 FGF23; fibroblast growth factor 23 [KO:K22428 ]
3479 IGF1; insulin like growth factor 1 [KO:K05459 ]
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 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
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 ]
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 ]
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 ]
1026 CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
4791 NFKB2; nuclear factor kappa B subunit 2 [KO:K04469 ]
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 ]
324 APC; APC regulator of WNT signaling pathway [KO:K02085 ]
10297 APC2; APC regulator of WNT signaling pathway 2 [KO:K02085 ]
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 ]
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 ]
5925 RB1; RB transcriptional corepressor 1 [KO:K06618 ]
675 BRCA2; BRCA2 DNA repair associated [KO:K08775 ]
Compound
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Zhang MH, Man HT, Zhao XD, Dong N, Ma SL
Title
Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review).
Journal
Reference
Authors
Dai X, Xiang L, Li T, Bai Z
Title
Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.
Journal
Reference
Authors
Schnitt SJ
Title
Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy.
Journal
Reference
Authors
Title
Comprehensive molecular portraits of human breast tumours.
Journal
Reference
Authors
Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A
Title
Molecular biology in breast cancer: intrinsic subtypes and signaling pathways.
Journal
Reference
Authors
Karamouzis MV, Papavassiliou KA, Adamopoulos C, Papavassiliou AG.
Title
Targeting androgen/estrogen receptors crosstalk in cancer
Journal
Reference
Authors
Sharp A, Harper-Wynne C.
Title
Treatment of advanced breast cancer (ABC): the expanding landscape of targeted therapies
Journal
J Cancer Biol Res 2:1036 (2014)
Reference
Authors
Byler S, Goldgar S, Heerboth S, Leary M, Housman G, Moulton K, Sarkar S
Title
Genetic and epigenetic aspects of breast cancer progression and therapy.
Journal
Anticancer Res 34:1071-7 (2014)
Reference
Authors
Mohamed A, Krajewski K, Cakar B, Ma CX
Title
Targeted therapy for breast cancer.
Journal
Reference
Authors
Ellis MJ, Ding L, Shen D, Luo J, Suman VJ, Wallis JW, Van Tine BA, Hoog J, Goiffon RJ, Goldstein TC, Ng S, Lin L, Crowder R, Snider J, Ballman K, Weber J, Chen K, Koboldt DC, Kandoth C, Schierding WS, McMichael JF, Miller CA, Lu C, Harris CC, McLellan MD, Wendl MC, DeSchryver K, Allred DC, Esserman L, Unzeitig G, Margenthaler J, Babiera GV, Marcom PK, Guenther JM, Leitch M, Hunt K, Olson J, Tao Y, Maher CA, Fulton LL, Fulton RS, Harrison M, Oberkfell B, Du F, Demeter R, Vickery TL, Elhammali A, Piwnica-Worms H, McDonald S, Watson M, Dooling DJ, Ota D, Chang LW, Bose R, Ley TJ, Piwnica-Worms D, Stuart JM, Wilson RK, Mardis ER
Title
Whole-genome analysis informs breast cancer response to aromatase inhibition.
Journal
Reference
Authors
Ma CX, Reinert T, Chmielewska I, Ellis MJ
Title
Mechanisms of aromatase inhibitor resistance.
Journal
Reference
Authors
Butt AJ, McNeil CM, Musgrove EA, Sutherland RL
Title
Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E.
Journal
Reference
Authors
Dasgupta S, Lonard DM, O'Malley BW
Title
Nuclear receptor coactivators: master regulators of human health and disease.
Journal
Reference
Authors
Brisken C
Title
Progesterone signalling in breast cancer: a neglected hormone coming into the limelight.
Journal
Reference
Authors
Scarpin KM, Graham JD, Mote PA, Clarke CL
Title
Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression.
Journal
Reference
Authors
Knutson TP, Lange CA
Title
Tracking progesterone receptor-mediated actions in breast cancer.
Journal
Reference
Authors
Dittrich A, Gautrey H, Browell D, Tyson-Capper A
Title
The HER2 Signaling Network in Breast Cancer--Like a Spider in its Web.
Journal
Reference
Authors
Higgins MJ, Baselga J
Title
Targeted therapies for breast cancer.
Journal
Reference
Authors
Mukohara T
Title
PI3K mutations in breast cancer: prognostic and therapeutic implications.
Journal
Reference
Authors
Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, Sledge GW, Carey LA
Title
Triple-negative breast cancer: risk factors to potential targets.
Journal
Reference
Authors
King TD, Suto MJ, Li Y
Title
The Wnt/beta-catenin signaling pathway: a potential therapeutic target in the treatment of triple negative breast cancer.
Journal
Reference
Authors
Brown AM
Title
Wnt signaling in breast cancer: have we come full circle?
Journal
Reference
Authors
Geyer FC, Lacroix-Triki M, Savage K, Arnedos M, Lambros MB, MacKay A, Natrajan R, Reis-Filho JS
Title
beta-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation.
Journal
Reference
Authors
Al-Hussaini H, Subramanyam D, Reedijk M, Sridhar SS
Title
Notch signaling pathway as a therapeutic target in breast cancer.
Journal
Reference
Authors
Rangel MC, Bertolette D, Castro NP, Klauzinska M, Cuttitta F, Salomon DS
Title
Developmental signaling pathways regulating mammary stem cells and contributing to the etiology of triple-negative breast cancer.
Journal
Reference
Authors
Jamdade VS, Sethi N, Mundhe NA, Kumar P, Lahkar M, Sinha N
Title
Therapeutic targets of triple-negative breast cancer: a review.
Journal
Reference
Authors
Karamboulas C, Ailles L
Title
Developmental signaling pathways in cancer stem cells of solid tumors.
Journal
Reference
Authors
Ignatiadis M, Sotiriou C
Title
Luminal breast cancer: from biology to treatment.
Journal
Reference
Authors
Shin SJ, Gong G, Lee HJ, Kang J, Bae YK, Lee A, Cho EY, Lee JS, Suh KS, Lee DW, Jung WH
Title
Positive expression of insulin-like growth factor-1 receptor is associated with a positive hormone receptor status and a favorable prognosis in breast cancer.
Journal
Reference
Authors
Gasco M, Shami S, Crook T
Title
The p53 pathway in breast cancer.
Journal
Reference
Authors
Narod SA, Foulkes WD
Title
BRCA1 and BRCA2: 1994 and beyond.
Journal
Related pathway
KO pathway