Entry Name Breast cancer
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 typesBRITE hierarchy
Pathway map Disease Orthology K00182 WNT2; wingless-type MMTV integration site family, member 2
K00312 WNT3; wingless-type MMTV integration site family, member 3
K00408 WNT4; wingless-type MMTV integration site family, member 4
K00444 WNT5; wingless-type MMTV integration site family, member 5
K00445 WNT6; wingless-type MMTV integration site family, member 6
K00572 WNT7; wingless-type MMTV integration site family, member 7
K00714 WNT8; wingless-type MMTV integration site family, member 8
K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01064 WNT9; wingless-type MMTV integration site family, member 9
K01357 WNT10; wingless-type MMTV integration site family, member 10
K01384 WNT11; wingless-type MMTV integration site family, member 11
K01558 WNT16; wingless-type MMTV integration site family, member 16
K02085 APC; adenomatosis polyposis coli protein
K02159 BAX; apoptosis regulator BAX
K02353 DVL; segment polarity protein dishevelled
K02354 FZD4, fz4, CD344; frizzled 4
K02375 FZD5_8, fz2; frizzled 5/8
K02432 FZD1_7, fz; frizzled 1/7
K02620 TCF7, TCF-1; transcription factor 7
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02842 FZD9_10, CD349_50; frizzled 9/10
K03068 LRP5_6; low density lipoprotein receptor-related protein 5/6
K03069 FRAT1; frequently rearranged in advanced T-cell lymphomas 1
K03096 FRAT2; frequently rearranged in advanced T-cell lymphomas 2
K03209 WNT1; wingless-type MMTV integration site family, member 1
K04357 EGF; epidermal growth factor
K04358 FGF; fibroblast growth factor
K04362 FGFR1, CD331; fibroblast growth factor receptor 1 [EC:2.7.10.1 ]
K04364 GRB2; growth factor receptor-bound protein 2
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04377 MYC; Myc proto-oncogene protein
K04379 FOS; proto-oncogene protein c-fos
K04402 GADD45; growth arrest and DNA-damage-inducible protein
K04448 JUN; transcription factor AP-1
K04451 TP53, P53; tumor protein p53
K04469 NFKB2; nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
K04490 TCF7L1; transcription factor 7-like 1
K04491 TCF7L2; transcription factor 7-like 2
K04492 LEF1; lymphoid enhancer-binding factor 1
K04503 CCND1; G1/S-specific cyclin-D1
K04684 SP1; transcription factor Sp1
K05083 ERBB2, HER2, CD340; receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1 ]
K05087 IGF1R, CD221; insulin-like growth factor 1 receptor [EC:2.7.10.1 ]
K05091 KIT, SCFR, CD117; proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1 ]
K05459 IGF1; insulin-like growth factor 1
K05473 TNFSF11, RANKL, CD254; tumor necrosis factor ligand superfamily member 11
K06054 HES1; hairy and enhancer of split 1
K06055 HES5; hairy and enhancer of split 5
K06279 SHC1; SHC-transforming protein 1
K06618 RB1; retinoblastoma-associated protein
K06620 E2F3; transcription factor E2F3
K06625 CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K07203 MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1 ]
K07827 KRAS, KRAS2; GTPase KRas
K08550 ESR1, NR3A1; estrogen receptor alpha
K08551 ESR2, NR3A2; estrogen receptor beta
K08556 PGR, NR3C3; progesterone receptor
K08775 BRCA2, FANCD1; breast cancer 2 susceptibility protein
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K09091 HEY; hairy and enhancer of split related with YRPW motif
K09101 NCOA1, SRC1, KAT13A; nuclear receptor coactivator 1 [EC:2.3.1.48 ]
K09389 E2F2; transcription factor E2F2
K10140 DDB2; DNA damage-binding protein 2
K10605 BRCA1; breast cancer type 1 susceptibility protein [EC:2.3.2.27 ]
K11256 NCOA3, ACTR, KAT13B; nuclear receptor coactivator 3 [EC:2.3.1.48 ]
K14021 BAK, BAK1; Bcl-2 homologous antagonist/killer
K17447 SHC2; SHC-transforming protein 2
K17448 SHC3; SHC-transforming protein 3
K17449 SHC4; SHC-transforming protein 4
K17454 E2F1; transcription factor E2F1
K18496 FGF1; fibroblast growth factor 1
K18497 FGF2; fibroblast growth factor 2
K22428 FGF23; fibroblast growth factor 23
K22429 FGF21; fibroblast growth factor 21
K22603 FGF19; fibroblast growth factor 19
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.
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