KEGG PATHWAY: ko05224

PATHWAY: ko05224

Entry

ko05224                     Pathway

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 types

Pathway map

ko05224

Breast cancer

Disease

H00031

Breast cancer

Orthology

K08550

estrogen receptor alpha

K08551

estrogen receptor beta

K09101

nuclear receptor coactivator 1 [EC:2.3.1.48]

K11256

nuclear receptor coactivator 3 [EC:2.3.1.48]

K04379

proto-oncogene protein c-fos

K04448

transcription factor AP-1

K04684

transcription factor Sp1

K04503

G1/S-specific cyclin-D1

K04377

Myc proto-oncogene protein

K08556

progesterone receptor

K03209

wingless-type MMTV integration site family, member 1

K00408

wingless-type MMTV integration site family, member 4

K05473

tumor necrosis factor ligand superfamily member 11

K05083

receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]

K18496

fibroblast growth factor 1

K18497

fibroblast growth factor 2

K04358

fibroblast growth factor

K22603

fibroblast growth factor 19

K22429

fibroblast growth factor 21

K22428

fibroblast growth factor 23

K04362

fibroblast growth factor receptor 1 [EC:2.7.10.1]

K05459

insulin-like growth factor 1

K05087

insulin-like growth factor 1 receptor [EC:2.7.10.1]

K04357

epidermal growth factor

K04361

epidermal growth factor receptor [EC:2.7.10.1]

K05091

proto-oncogene tyrosine-protein kinase Kit [EC:2.7.10.1]

K06279

SHC-transforming protein 1

K17447

SHC-transforming protein 2

K17448

SHC-transforming protein 3

K17449

SHC-transforming protein 4

K04364

growth factor receptor-bound protein 2

K03099

son of sevenless

K02833

GTPase HRas

K07827

GTPase KRas

K07828

GTPase NRas

K08845

A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04365

B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04366

RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04368

mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]

K04369

mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]

K04371

mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K00922

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K02649

phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K01110

phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.16 3.1.3.48 3.1.3.67]

K04456

RAC serine/threonine-protein kinase [EC:2.7.11.1]

K07203

serine/threonine-protein kinase mTOR [EC:2.7.11.1]

K04688

ribosomal protein S6 kinase beta [EC:2.7.11.1]

K06052

jagged-1

K21635

jagged-2

K06051

delta

K02599

Notch 1

K20994

Notch 2

K20995

Notch 3

K20996

Notch 4

K06054

hairy and enhancer of split 1

K06055

hairy and enhancer of split 5

K09091

hairy and enhancer of split related with YRPW motif

K05097

FMS-like tyrosine kinase 4 [EC:2.7.10.1]

K06625

cyclin-dependent kinase inhibitor 1A

K04469

nuclear factor of kappa light polypeptide gene enhancer in B-cells 2

K00182

wingless-type MMTV integration site family, member 2

K00312

wingless-type MMTV integration site family, member 3

K00444

wingless-type MMTV integration site family, member 5

K00445

wingless-type MMTV integration site family, member 6

K00572

wingless-type MMTV integration site family, member 7

K00714

wingless-type MMTV integration site family, member 8

K01064

wingless-type MMTV integration site family, member 9

K01357

wingless-type MMTV integration site family, member 10

K01384

wingless-type MMTV integration site family, member 11

K01558

wingless-type MMTV integration site family, member 16

K02432

frizzled 1/7

K02235

frizzled 2

K02329

frizzled 3

K02354

frizzled 4

K02375

frizzled 5/8

K02376

frizzled 6

K02842

frizzled 9/10

K03068

low density lipoprotein receptor-related protein 5/6

K02353

segment polarity protein dishevelled

K03069

frequently rearranged in advanced T-cell lymphomas 1

K03096

frequently rearranged in advanced T-cell lymphomas 2

K03083

glycogen synthase kinase 3 beta [EC:2.7.11.26]

K02157

axin 1

K04385

axin 2

K02085

adenomatosis polyposis coli protein

K02105

catenin beta 1

K08957

casein kinase 1, alpha [EC:2.7.11.1]

K02620

transcription factor 7

K04490

transcription factor 7-like 1

K04491

transcription factor 7-like 2

K04492

lymphoid enhancer-binding factor 1

K04451

tumor protein p53

K04402

growth arrest and DNA-damage-inducible protein

K02159

apoptosis regulator BAX

K14021

Bcl-2 homologous antagonist/killer

K10140

DNA damage-binding protein 2

K03511

DNA polymerase kappa [EC:2.7.7.7]

K02089

cyclin-dependent kinase 4 [EC:2.7.11.22]

K02091

cyclin-dependent kinase 6 [EC:2.7.11.22]

K06618

retinoblastoma-associated protein

K17454

transcription factor E2F1

K09389

transcription factor E2F2

K06620

transcription factor E2F3

K10605

breast cancer type 1 susceptibility protein [EC:2.3.2.27]

K08775

breast cancer 2 susceptibility protein

Compound

C00410

Progesterone

C00951

Estradiol-17beta

C05981

Phosphatidylinositol-3,4,5-trisphosphate

Reference

PMID:24649067

Authors

Zhang MH, Man HT, Zhao XD, Dong N, Ma SL

Title

Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review).

Journal

Biomed Rep 2:41-52 (2014)
DOI:10.3892/br.2013.187

Reference

PMID:27390604

Authors

Dai X, Xiang L, Li T, Bai Z

Title

Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.

Journal

J Cancer 7:1281-94 (2016)
DOI:10.7150/jca.13141

Reference

PMID:20436504

Authors

Schnitt SJ

Title

Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy.

Journal

Mod Pathol 23 Suppl 2:S60-4 (2010)
DOI:10.1038/modpathol.2010.33

Reference

PMID:23000897

Authors

Title

Comprehensive molecular portraits of human breast tumours.

Journal

Nature 490:61-70 (2012)
DOI:10.1038/nature11412

Reference

PMID:22178455

Authors

Eroles P, Bosch A, Perez-Fidalgo JA, Lluch A

Title

Molecular biology in breast cancer: intrinsic subtypes and signaling pathways.

Journal

Cancer Treat Rev 38:698-707 (2012)
DOI:10.1016/j.ctrv.2011.11.005

Reference

Authors

Karamouzis MV, Papavassiliou KA, Adamopoulos C, Papavassiliou AG.

Title

Targeting androgen/estrogen receptors crosstalk in cancer

Journal

Trends Cancer 2:35-48 (2016)
DOI:10.1016/j.trecan.2015.12.001

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

PMID:24596345

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

PMID:23988612

Authors

Mohamed A, Krajewski K, Cakar B, Ma CX

Title

Targeted therapy for breast cancer.

Journal

Am J Pathol 183:1096-112 (2013)
DOI:10.1016/j.ajpath.2013.07.005

Reference

PMID:22722193

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

Nature 486:353-60 (2012)
DOI:10.1038/nature11143

Reference

PMID:25907219

Authors

Ma CX, Reinert T, Chmielewska I, Ellis MJ

Title

Mechanisms of aromatase inhibitor resistance.

Journal

Nat Rev Cancer 15:261-75 (2015)
DOI:10.1038/nrc3920

Reference

PMID:16113099

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

Endocr Relat Cancer 12 Suppl 1:S47-59 (2005)
DOI:10.1677/erc.1.00993

Reference

PMID:24111892

Authors

Dasgupta S, Lonard DM, O'Malley BW

Title

Nuclear receptor coactivators: master regulators of human health and disease.

Journal

Annu Rev Med 65:279-92 (2014)
DOI:10.1146/annurev-med-051812-145316

Reference

PMID:23702927

Authors

Brisken C

Title

Progesterone signalling in breast cancer: a neglected hormone coming into the limelight.

Journal

Nat Rev Cancer 13:385-96 (2013)
DOI:10.1038/nrc3518

Reference

PMID:20087430

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

Nucl Recept Signal 7:e009 (2009)
DOI:10.1621/nrs.07009

Reference

PMID:24291072

Authors

Knutson TP, Lange CA

Title

Tracking progesterone receptor-mediated actions in breast cancer.

Journal

Pharmacol Ther 142:114-25 (2014)
DOI:10.1016/j.pharmthera.2013.11.010

Reference

PMID:25544707

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

J Mammary Gland Biol Neoplasia 19:253-70 (2014)
DOI:10.1007/s10911-014-9329-5

Reference

PMID:21965336

Authors

Higgins MJ, Baselga J

Title

Targeted therapies for breast cancer.

Journal

J Clin Invest 121:3797-803 (2011)
DOI:10.1172/JCI57152

Reference

PMID:26028978

Authors

Mukohara T

Title

PI3K mutations in breast cancer: prognostic and therapeutic implications.

Journal

Breast Cancer (Dove Med Press) 7:111-23 (2015)
DOI:10.2147/BCTT.S60696

Reference

PMID:19088017

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

Clin Cancer Res 14:8010-8 (2008)
DOI:10.1158/1078-0432.CCR-08-1208

Reference

PMID:21898546

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

J Cell Biochem 113:13-8 (2012)
DOI:10.1002/jcb.23350

Reference

PMID:11737884

Authors

Brown AM

Title

Wnt signaling in breast cancer: have we come full circle?

Journal

Breast Cancer Res 3:351-5 (2001)
DOI:10.1186/bcr321

Reference

PMID:21076461

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

Mod Pathol 24:209-31 (2011)
DOI:10.1038/modpathol.2010.205

Reference

PMID:20971825

Authors

Al-Hussaini H, Subramanyam D, Reedijk M, Sridhar SS

Title

Notch signaling pathway as a therapeutic target in breast cancer.

Journal

Mol Cancer Ther 10:9-15 (2011)
DOI:10.1158/1535-7163.MCT-10-0677

Reference

PMID:26968398

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

Breast Cancer Res Treat 156:211-26 (2016)
DOI:10.1007/s10549-016-3746-7

Reference

PMID:26040571

Authors

Jamdade VS, Sethi N, Mundhe NA, Kumar P, Lahkar M, Sinha N

Title

Therapeutic targets of triple-negative breast cancer: a review.

Journal

Br J Pharmacol 172:4228-37 (2015)
DOI:10.1111/bph.13211

Reference

PMID:23196196

Authors

Karamboulas C, Ailles L

Title

Developmental signaling pathways in cancer stem cells of solid tumors.

Journal

Biochim Biophys Acta 1830:2481-95 (2013)
DOI:10.1016/j.bbagen.2012.11.008

Reference

PMID:23881035

Authors

Ignatiadis M, Sotiriou C

Title

Luminal breast cancer: from biology to treatment.

Journal

Nat Rev Clin Oncol 10:494-506 (2013)
DOI:10.1038/nrclinonc.2013.124

Reference

PMID:25013431

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

J Breast Cancer 17:113-20 (2014)
DOI:10.4048/jbc.2014.17.2.113

Reference

PMID:11879567

Authors

Gasco M, Shami S, Crook T

Title

The p53 pathway in breast cancer.

Journal

Breast Cancer Res 4:70-6 (2002)
DOI:10.1186/bcr426

Reference

PMID:15343273