Entry |
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Name |
Breast cancer - Homo sapiens (human)
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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.
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Class |
Human Diseases; Cancer: specific types
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Pathway map |

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Network |
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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 |
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Disease |
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Drug |
D00554 | Ethinyl estradiol (USP) |
D00951 | Medroxyprogesterone acetate (JP17/USP) |
D00966 | Tamoxifen citrate (JP17/USP) |
D00967 | Toremifene citrate (JAN/USAN) |
D01161 | Fulvestrant (JAN/USP/INN) |
D01602 | Mepitiostane (JP17/INN) |
D02714 | Everolimus (JAN/USAN/INN) |
D04024 | Lapatinib ditosylate (USAN) |
D09980 | Trastuzumab emtansine (USAN/INN) |
D10979 | Ribociclib succinate (USAN) |
D11011 | Alpelisib (JAN/USAN/INN) |
D11672 | Elacestrant hydrochloride (USAN) |
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Organism |
Homo sapiens (human) [GN: hsa]
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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] |
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Compound |
C05981 | Phosphatidylinositol-3,4,5-trisphosphate |
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Reference |
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Authors |
Zhang MH, Man HT, Zhao XD, Dong N, Ma SL |
Title |
Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review). |
Journal |
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Reference |
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Authors |
Dai X, Xiang L, Li T, Bai Z |
Title |
Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes. |
Journal |
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Reference |
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Authors |
Schnitt SJ |
Title |
Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy. |
Journal |
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Reference |
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Authors |
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Title |
Comprehensive molecular portraits of human breast tumours. |
Journal |
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Reference |
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Authors |
Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A |
Title |
Molecular biology in breast cancer: intrinsic subtypes and signaling pathways. |
Journal |
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Reference |
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Authors |
Karamouzis MV, Papavassiliou KA, Adamopoulos C, Papavassiliou AG. |
Title |
Targeting androgen/estrogen receptors crosstalk in cancer |
Journal |
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Reference |
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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 |
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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 |
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Authors |
Mohamed A, Krajewski K, Cakar B, Ma CX |
Title |
Targeted therapy for breast cancer. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Ma CX, Reinert T, Chmielewska I, Ellis MJ |
Title |
Mechanisms of aromatase inhibitor resistance. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Dasgupta S, Lonard DM, O'Malley BW |
Title |
Nuclear receptor coactivators: master regulators of human health and disease. |
Journal |
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Reference |
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Authors |
Brisken C |
Title |
Progesterone signalling in breast cancer: a neglected hormone coming into the limelight. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Knutson TP, Lange CA |
Title |
Tracking progesterone receptor-mediated actions in breast cancer. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Higgins MJ, Baselga J |
Title |
Targeted therapies for breast cancer. |
Journal |
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Reference |
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Authors |
Mukohara T |
Title |
PI3K mutations in breast cancer: prognostic and therapeutic implications. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Brown AM |
Title |
Wnt signaling in breast cancer: have we come full circle? |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Al-Hussaini H, Subramanyam D, Reedijk M, Sridhar SS |
Title |
Notch signaling pathway as a therapeutic target in breast cancer. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Jamdade VS, Sethi N, Mundhe NA, Kumar P, Lahkar M, Sinha N |
Title |
Therapeutic targets of triple-negative breast cancer: a review. |
Journal |
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Reference |
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Authors |
Karamboulas C, Ailles L |
Title |
Developmental signaling pathways in cancer stem cells of solid tumors. |
Journal |
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Reference |
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Authors |
Ignatiadis M, Sotiriou C |
Title |
Luminal breast cancer: from biology to treatment. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Gasco M, Shami S, Crook T |
Title |
The p53 pathway in breast cancer. |
Journal |
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Reference |
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Authors |
Narod SA, Foulkes WD |
Title |
BRCA1 and BRCA2: 1994 and beyond. |
Journal |
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Related pathway |
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KO pathway |
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LinkDB |
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