Breast-Ovarian Cancer, Familial, Susceptibility To, 4

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

BRCA1, BRCA2, TP53, RAD51C, CHEK2, PALB2, RAD51D, BRIP1, MRE11, BARD1, NBN, PTEN, RAD50, RAD51, ATM, MLH1, ABRAXAS1, RAD51B, RPL21P4, C11orf65, MSH6, MSH2, PMS2, KRT88P, KRAS, PRSS1, BRCA3, MRC1, AR, WT1, SEM1, VHL, PARP1, RASSF7, ALYREF, HOXB13, RNU1-4, OLA1, HSD17B7, BCCIP, EMSY, DHRS11, SLC22A12, HSD17B13, MIR146A, S100A2, PMS1, RB1, FANCC, APRT, CDH1, CDK2, CDKN2A, COL11A2, CRYGD, DHX8, EPHA3, ERBB2, ERCC4, FANCA, FAP, RAD52, HRAS, HSD11B2, HSD17B1, IGFBP4, KIT, MFAP1, MSH3, NF2, NOTCH3, NRAS, APC, LOC111589215

Drugs

(5S,8S,10aR)-N-benzhydryl-5-((S)-2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide, 8-[4-(1-aminocyclobutyl)phenyl]-9-phenyl-1,2,4-triazolo[3,4-f][1,6]naphthyridin-3(2H)-one mono-hydrochloride, Abagovomab, Adenovirus-associated vector containing human Fas-c gene, Anti-EphA2 monoclonal antibody conjugated to maleimidocaproyl monomethylauristatin phenylalanine, Bevacizumab ( Equidacent, AVASTIN, Aybintio, MVASI ), Defactinib, Doxorubicin hydrochloride (pegylated liposomal) ( CAELYX, DOXORUBICINE TEVA ), Imexon, Maytansinoid-conjugated human monoclonal antibody against mesothelin, Mibefradil, Olaparib ( LYNPARZA ), Patupilone (Epothilone B), Plevitrexed, Pyr-His-Trp-Ser-Tyr-D-Lys(doxorubicinylglutarate)-Leu-Arg-Pro-Gly-NH2, acetate salt, Rucaparib ( RUBRACA ), Treosulfan ( TRECONDI ), Vaccine consisting of 5 survivin peptides with different human leukocyte antigen restrictions, autologous dendritic cells pulsed with killed ovarian cancer cells and matured by TLR3 ligand ex vivo, human reovirus type 3 Dearing strain, humanised anti-folate receptor 1 monoclonal antibody conjugated to maytansinoid DM4

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A number sign (#) is used with this entry because of evidence that susceptibility to familial breast-ovarian cancer-4 (BROVCA4) results from heterozygous germline mutation in the RAD51D gene (602954) on chromosome 17q11.

For a discussion of genetic heterogeneity of breast-ovarian cancer susceptibility, see BROVCA1 (604370).

For general discussions of breast cancer and ovarian cancer, see 114480 and 167000, respectively.

Clinical Features

Loveday et al. (2011) identified 8 families with breast-ovarian cancer associated with mutation in the RAD51D gene. Pathology information was available for 4 ovarian cancers from RAD51D mutation carriers; 3 of the cancers were serous adenocarcinoma and 1 was an endometrioid cancer. Of 8 breast cancers for which pathologic information was available, 7 were ductal in origin and 1 was a carcinoma with medullary features. Receptor status was available from 5 breast cancers, of which 3 were estrogen-receptor (see 133430)-positive and 2 negative.

Molecular Genetics

Loveday et al. (2011) investigated the role of RAD51D in cancer susceptibility and identified 8 inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with 1 inactivating mutation identified in 1,060 controls (P = 0.01). The association was found principally with ovarian cancer, with 3 mutations identified in the 59 pedigrees with 3 or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 x 10(-6)). By contrast, Loveday et al. (2011) estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). Loveday et al. (2011) concluded that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. They also demonstrated that cells deficient in RAD51D are sensitive to treatment with a PARP (173870) inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers. Loveday et al. (2011) identified nonsense, frameshift, and missense mutations in RAD51D patients with a family history of breast and predominantly ovarian cancer (e.g., 602954.0001).