Entry

H00031                      Disease

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.

Category

Cancer

Brite

Human diseases [BR:br08402]
Cancers
  Cancers of the breast and female genital organs
   H00031  Breast cancer
Human diseases in ICD-11 classification [BR:br08403]
02 Neoplasms
  Malignant neoplasms, except primary neoplasms of lymphoid, haematopoietic, central nervous system or related tissues
   Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
    Malignant neoplasms of breast
     2C61  Invasive carcinoma of breast
      H00031  Breast cancer
Tumor markers [br08442.html]
H00031
Cancer-associated carbohydrates [br08441.html]
H00031

Pathway

hsa05224

Breast cancer

Related
pathway

hsa03440

Homologous recombination

hsa03460

Fanconi anemia pathway

hsa04151

PI3K-Akt signaling pathway

Network

nt06270  Breast cancer
nt06506  Double-strand break repair
nt06508  Interstrand crosslink repair

Gene

BRCA1 (germline mutation, hypermethylation) [HSA:672] [KO:K10605]
BRCA2 [HSA:675] [KO:K08775]
BARD1 [HSA:580] [KO:K10683]
BRIP1 [HSA:83990] [KO:K15362]
PALB2 [HSA:79728] [KO:K10897]
RAD51 [HSA:5888] [KO:K04482]
RAD54L [HSA:8438] [KO:K10875]
XRCC3 [HSA:7517] [KO:K10880]
ERBB2/HER2 (overexpression) [HSA:2064] [KO:K05083]
ESR1/ER1 [HSA:2099] [KO:K08550]
PGR [HSA:5241] [KO:K08556]
GATA3 [HSA:2625] [KO:K17895]
PIK3CA [HSA:5290] [KO:K00922]
TP53 [HSA:7157] [KO:K04451]
PPM1D [HSA:8493] [KO:K10147]
RB1CC1 [HSA:9821] [KO:K17589]
HMMR [HSA:3161] [KO:K06267]
NQO2 [HSA:4835] [KO:K08071]
SLC22A18 [HSA:5002] [KO:K08214]
PTEN [HSA:5728] [KO:K01110]
EGFR (overexpression) [HSA:1956] [KO:K04361]
KIT (overexpression) [HSA:3815] [KO:K05091]
NOTCH1 (overexpression) [HSA:4851] [KO:K02599]
NOTCH4 (overexpression) [HSA:4855] [KO:K20996]
FZD7 (overexpression) [HSA:8324] [KO:K02432]
LRP6 (overexpression) [HSA:4040] [KO:K03068]
FGFR1 (amplification) [HSA:2260] [KO:K04362]
CCND1 (amplification) [HSA:595] [KO:K04503]

Drug

Fluoxymesterone [DR:D00327]
Methyltestosterone [DR:D00408]
Testosterone enanthate [DR:D00958]
Cyclophosphamide [DR:D00287]
Thiotepa [DR:D00583]
Methotrexate sodium [DR:D02115]
Gemcitabine hydrochloride [DR:D01155]
Capecitabine [DR:D01223]
Vinblastine sulfate [DR:D01068]
Paclitaxel [DR:D00491]
Docetaxel [DR:D07866]
Docetaxel [DR:D02165]
Doxorubicin hydrochloride [DR:D01275]
Epirubicin hydrochloride [DR:D02214]
Ixabepilone [DR:D04645]
Palbociclib [DR:D10372] (HR positive, HER2 negative)
Ribociclib succinate [DR:D10979] (HR-positive, HER2-negative)
Abemaciclib [DR:D10688] (HR positive, HER2 negative)
Everolimus [DR:D02714] (HR positive, HER2 negative)
Lapatinib ditosylate [DR:D04024] (HER2 overexpressing)
Neratinib maleate [DR:D10898] (HER2 positive)
Tucatinib [DR:D11141] (HER2 positive)
Alpelisib [DR:D11011] (HR-positive, HER2-negative, PIK3CA-mutated)
Trastuzumab [DR:D03257] (HER2 overexpressing)
Pertuzumab [DR:D05446] (HER2 positive)
Trastuzumab emtansine [DR:D09980] (HER2 positive)
Trastuzumab deruxtecan [DR:D11529] (HER2 positive)
Pembrolizumab [DR:D10574] (triple-negative, PD-L1 expressed)
Atezolizumab [DR:D10773] (PD-L1 expressed, HR negative, HER2 negative)
Sacituzumab govitecan [DR:D10985] (triple negative)
Olaparib [DR:D09730] (BRCA-mutated, HER2-negative)
Talazoparib tosylate [DR:D10733] (BRCA mutated, HER2 negative)
Eribulin mesylate [DR:D08914]
Pertuzumab, trastuzumab and hyaluronidase [DR:D11934]
Goserelin acetate [DR:D00573]
Tamoxifen citrate [DR:D00966] (ER-positive)
Toremifene citrate [DR:D00967] (ER-positive)
Fulvestrant [DR:D01161] (HR positive, HER2 negative)
Anastrozole [DR:D00960] (HR-positive or HR-unknown)
Letrozole [DR:D00964] (HR-positive)
Exemestane [DR:D00963] (ER-positive)
Estrogens, esterified [DR:D04071]
Margetuximab [DR:D10446] (HER2 positive)
Letrozole and ribociclib [DR:D11068] (HR positive, HER2 negative)
Trastuzumab and hyaluronidase [DR:D11560] (HER2 overexpressing or ER/PR negative)

Other DBs

ICD-11:

2C61

ICD-10:

C50

MeSH:

D001943

OMIM:

114480

Reference

PMID:28976962 (BRCA1, BARD1, RAD51)

Authors

Zhao W, Steinfeld JB, Liang F, Chen X, Maranon DG, Jian Ma C, Kwon Y, Rao T, Wang W, Sheng C, Song X, Deng Y, Jimenez-Sainz J, Lu L, Jensen RB, Xiong Y, Kupfer GM, Wiese C, Greene EC, Sung P

Title

BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing.

Journal

Nature 550:360-365 (2017)
DOI:10.1038/nature24060

Reference

PMID:9425226 (BARD1)

Authors

Thai TH, Du F, Tsan JT, Jin Y, Phung A, Spillman MA, Massa HF, Muller CY, Ashfaq R, Mathis JM, Miller DS, Trask BJ, Baer R, Bowcock AM

Title

Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers.

Journal

Hum Mol Genet 7:195-202 (1998)
DOI:10.1093/hmg/7.2.195

Reference

PMID:29368626 (BRIP1)

Authors

Weber-Lassalle N, Hauke J, Ramser J, Richters L, Gross E, Blumcke B, Gehrig A, Kahlert AK, Muller CR, Hackmann K, Honisch E, Weber-Lassalle K, Niederacher D, Borde J, Thiele H, Ernst C, Altmuller J, Neidhardt G, Nurnberg P, Klaschik K, Schroeder C, Platzer K, Volk AE, Wang-Gohrke S, Just W, Auber B, Kubisch C, Schmidt G, Horvath J, Wappenschmidt B, Engel C, Arnold N, Dworniczak B, Rhiem K, Meindl A, Schmutzler RK, Hahnen E

Title

BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer.

Journal

Breast Cancer Res 20:7 (2018)
DOI:10.1186/s13058-018-0935-9

Reference

PMID:24556926 (PALB2)

Authors

Catucci I, Peterlongo P, Ciceri S, Colombo M, Pasquini G, Barile M, Bonanni B, Verderio P, Pizzamiglio S, Foglia C, Falanga A, Marchetti M, Galastri L, Bianchi T, Corna C, Ravagnani F, Bernard L, Fortuzzi S, Sardella D, Scuvera G, Peissel B, Manoukian S, Tondini C, Radice P

Title

PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo.

Journal

Genet Med 16:688-94 (2014)
DOI:10.1038/gim.2014.13

Reference

PMID:10362365 (RAD54L)

Authors

Matsuda M, Miyagawa K, Takahashi M, Fukuda T, Kataoka T, Asahara T, Inui H, Watatani M, Yasutomi M, Kamada N, Dohi K, Kamiya K

Title

Mutations in the RAD54 recombination gene in primary cancers.

Journal

Oncogene 18:3427-30 (1999)
DOI:10.1038/sj.onc.1202692

Reference

PMID:12023982 (XRCC3)

Authors

Kuschel B, Auranen A, McBride S, Novik KL, Antoniou A, Lipscombe JM, Day NE, Easton DF, Ponder BA, Pharoah PD, Dunning A

Title

Variants in DNA double-strand break repair genes and breast cancer susceptibility.

Journal

Hum Mol Genet 11:1399-407 (2002)
DOI:10.1093/hmg/11.12.1399

Reference

PMID:10448115 (MYC, BRCA1, BRCA2, TP53, ERBB2)

Authors

Ingvarsson S.

Title

Molecular genetics of breast cancer progression.

Journal

Semin Cancer Biol 9:277-88 (1999)
DOI:10.1006/scbi.1999.0124

Reference

PMID:31106278 (ESR1, PIK3CA)

Authors

Lei JT, Gou X, Seker S, Ellis MJ

Title

ESR1 alterations and metastasis in estrogen receptor positive breast cancer.

Journal

J Cancer Metastasis Treat 5:38 (2019)
DOI:10.20517/2394-4722.2019.12

Reference

PMID:29302853 (PGR)

Authors

Ghali RM, Al-Mutawa MA, Ebrahim BH, Jrah HH, Zaied S, Bhiri H, Hmila F, Mahjoub T, Almawi WY

Title

Progesterone Receptor (PGR) Gene Variants Associated with Breast Cancer and Associated Features: a Case-Control Study.

Journal

Pathol Oncol Res 26:141-147 (2020)
DOI:10.1007/s12253-017-0379-z

Reference

PMID:23000897 (TP53, PIK3CA, GATA3)

Title

Comprehensive molecular portraits of human breast tumours.

Journal

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

Reference

PMID:21203526 (RB1CC1, TP53)

Authors

Chano T, Ikebuchi K, Tomita Y, Jin Y, Inaji H, Ishitobi M, Teramoto K, Ochi Y, Tameno H, Nishimura I, Minami K, Inoue H, Isono T, Saitoh M, Shimada T, Hisa Y, Okabe H

Title

RB1CC1 together with RB1 and p53 predicts long-term survival in Japanese breast cancer patients.

Journal

PLoS One 5:e15737 (2010)
DOI:10.1371/journal.pone.0015737

Reference

PMID:32231069 (HMMR)

Authors

He Z, Mei L, Connell M, Maxwell CA

Title

Hyaluronan Mediated Motility Receptor () Encodes an Evolutionarily Conserved Homeostasis, Mitosis, and Meiosis Regulator Rather than a Hyaluronan Receptor.

Journal

Cells 9:E819 (2020)
DOI:10.3390/cells9040819

Reference

PMID:19351655 (NQO2)

Authors

Yu KD, Di GH, Yuan WT, Fan L, Wu J, Hu Z, Shen ZZ, Zheng Y, Huang W, Shao ZM

Title

Functional polymorphisms, altered gene expression and genetic association link NRH:quinone oxidoreductase 2 to breast cancer with wild-type p53.

Journal

Hum Mol Genet 18:2502-17 (2009)
DOI:10.1093/hmg/ddp171

Reference

PMID:23242139 (PPM1D)

Authors

Ruark E, Snape K, Humburg P, Loveday C, Bajrami I, Brough R, Rodrigues DN, Renwick A, Seal S, Ramsay E, Duarte Sdel V, Rivas MA, Warren-Perry M, Zachariou A, Campion-Flora A, Hanks S, Murray A, Ansari Pour N, Douglas J, Gregory L, Rimmer A, Walker NM, Yang TP, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Eccles D, Evans DG, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, Gore M, Houlston R, Brown MA, Caufield MJ, Deloukas P, McCarthy MI, Todd JA, Turnbull C, Reis-Filho JS, Ashworth A, Antoniou AC, Lord CJ, Donnelly P, Rahman N

Title

Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer.

Journal

Nature 493:406-10 (2013)
DOI:10.1038/nature11725

Reference

PMID:9520460 (SLC22A18)

Authors

Schwienbacher C, Sabbioni S, Campi M, Veronese A, Bernardi G, Menegatti A, Hatada I, Mukai T, Ohashi H, Barbanti-Brodano G, Croce CM, Negrini M

Title

Transcriptional map of 170-kb region at chromosome 11p15.5: identification and mutational analysis of the BWR1A gene reveals the presence of mutations in tumor samples.

Journal

Proc Natl Acad Sci U S A 95:3873-8 (1998)
DOI:10.1073/pnas.95.7.3873

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: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: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:26040571 (EGFR, NOTCH1, NOTCH4, FZD7, LRP6)

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

DISEASE: Breast cancer