KEGG   DISEASE: Breast cancer
H00031                      Disease                                
Breast cancer
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, Wnt/beta-catenin, and EGFR) have been confirmed.
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
Pathway-based classification of diseases [BR:br08402]
 Replication and repair
  nt06506  Double-strand break repair
   H00031  Breast cancer
  nt06508  Interstrand crosslink repair
   H00031  Breast cancer
 Signal transduction
  nt06526  MAPK signaling
   H00031  Breast cancer
  nt06530  PI3K signaling
   H00031  Breast cancer
Tumor markers [br08442.html]
Cancer-associated carbohydrates [br08441.html]
hsa05224  Breast cancer
hsa03440  Homologous recombination
hsa03460  Fanconi anemia pathway
hsa04151  PI3K-Akt signaling pathway
nt06270 Breast cancer
nt06506 Double-strand break repair
nt06508 Interstrand crosslink repair
nt06530 PI3K signaling
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]
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)
Capivasertib [DR:D11371] (HR positive, HER2 negative, PIK3CA/AKT1/PTEN-mutated)
Trastuzumab [DR:D03257] (HER2 overexpressing)
Trastuzumab and hyaluronidase [DR:D11560] (HER2 overexpressing or ER/PR negative)
Pertuzumab [DR:D05446] (HER2 positive)
Trastuzumab emtansine [DR:D09980] (HER2 positive)
Trastuzumab deruxtecan [DR:D11529] (HER2 positive)
Margetuximab [DR:D10446] (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)
Pertuzumab, trastuzumab and hyaluronidase [DR:D11934]
Olaparib [DR:D09730] (BRCA-mutated, HER2-negative)
Talazoparib tosylate [DR:D10733] (BRCA mutated, HER2 negative)
Eribulin mesylate [DR:D08914]
Goserelin acetate [DR:D00573]
Tamoxifen citrate [DR:D00966] (ER-positive)
Toremifene citrate [DR:D00967] (ER-positive)
Fulvestrant [DR:D01161] (HR positive, HER2 negative)
Elacestrant hydrochloride [DR:D11672] (ER-positive, HER2 negative, ESR1-mutated)
Anastrozole [DR:D00960] (HR-positive or HR-unknown)
Letrozole [DR:D00964] (HR-positive)
Exemestane [DR:D00963] (ER-positive)
Estrogens, esterified [DR:D04071]
Letrozole and ribociclib [DR:D11068] (HR positive, HER2 negative)
Other DBs
ICD-11: 2C61
ICD-10: C50
MeSH: D001943
OMIM: 114480
PMID:28976962 (BRCA1, BARD1, RAD51)
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
BRCA1-BARD1 promotes RAD51-mediated homologous DNA pairing.
Nature 550:360-365 (2017)
PMID:9425226 (BARD1)
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
Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers.
Hum Mol Genet 7:195-202 (1998)
PMID:29368626 (BRIP1)
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
BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer.
Breast Cancer Res 20:7 (2018)
PMID:24556926 (PALB2)
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
PALB2 sequencing in Italian familial breast cancer cases reveals a high-risk mutation recurrent in the province of Bergamo.
Genet Med 16:688-94 (2014)
PMID:10362365 (RAD54L)
Matsuda M, Miyagawa K, Takahashi M, Fukuda T, Kataoka T, Asahara T, Inui H, Watatani M, Yasutomi M, Kamada N, Dohi K, Kamiya K
Mutations in the RAD54 recombination gene in primary cancers.
Oncogene 18:3427-30 (1999)
PMID:12023982 (XRCC3)
Kuschel B, Auranen A, McBride S, Novik KL, Antoniou A, Lipscombe JM, Day NE, Easton DF, Ponder BA, Pharoah PD, Dunning A
Variants in DNA double-strand break repair genes and breast cancer susceptibility.
Hum Mol Genet 11:1399-407 (2002)
PMID:10448115 (MYC, BRCA1, BRCA2, TP53, ERBB2)
Ingvarsson S.
Molecular genetics of breast cancer progression.
Semin Cancer Biol 9:277-88 (1999)
PMID:31106278 (ESR1, PIK3CA)
Lei JT, Gou X, Seker S, Ellis MJ
ESR1 alterations and metastasis in estrogen receptor positive breast cancer.
J Cancer Metastasis Treat 5:38 (2019)
PMID:29302853 (PGR)
Ghali RM, Al-Mutawa MA, Ebrahim BH, Jrah HH, Zaied S, Bhiri H, Hmila F, Mahjoub T, Almawi WY
Progesterone Receptor (PGR) Gene Variants Associated with Breast Cancer and Associated Features: a Case-Control Study.
Pathol Oncol Res 26:141-147 (2020)
PMID:23000897 (TP53, PIK3CA, GATA3)
Comprehensive molecular portraits of human breast tumours.
Nature 490:61-70 (2012)
PMID:21203526 (RB1CC1, TP53)
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
RB1CC1 together with RB1 and p53 predicts long-term survival in Japanese breast cancer patients.
PLoS One 5:e15737 (2010)
PMID:32231069 (HMMR)
He Z, Mei L, Connell M, Maxwell CA
Hyaluronan Mediated Motility Receptor () Encodes an Evolutionarily Conserved Homeostasis, Mitosis, and Meiosis Regulator Rather than a Hyaluronan Receptor.
Cells 9:E819 (2020)
PMID:19351655 (NQO2)
Yu KD, Di GH, Yuan WT, Fan L, Wu J, Hu Z, Shen ZZ, Zheng Y, Huang W, Shao ZM
Functional polymorphisms, altered gene expression and genetic association link NRH:quinone oxidoreductase 2 to breast cancer with wild-type p53.
Hum Mol Genet 18:2502-17 (2009)
PMID:23242139 (PPM1D)
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
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer.
Nature 493:406-10 (2013)
PMID:9520460 (SLC22A18)
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
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.
Proc Natl Acad Sci U S A 95:3873-8 (1998)
Dai X, Xiang L, Li T, Bai Z
Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes.
J Cancer 7:1281-94 (2016)
Zhang MH, Man HT, Zhao XD, Dong N, Ma SL
Estrogen receptor-positive breast cancer molecular signatures and therapeutic potentials (Review).
Biomed Rep 2:41-52 (2014)
Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, Sledge GW, Carey LA
Triple-negative breast cancer: risk factors to potential targets.
Clin Cancer Res 14:8010-8 (2008)
King TD, Suto MJ, Li Y
The Wnt/beta-catenin signaling pathway: a potential therapeutic target in the treatment of triple negative breast cancer.
J Cell Biochem 113:13-8 (2012)
PMID:26040571 (EGFR, NOTCH1, NOTCH4, FZD7, LRP6)
Jamdade VS, Sethi N, Mundhe NA, Kumar P, Lahkar M, Sinha N
Therapeutic targets of triple-negative breast cancer: a review.
Br J Pharmacol 172:4228-37 (2015)

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