Hereditary Ovarian Cancer and Risk Reduction

• Published in: Best practice & research. Clinical obstetrics & gynaecology Vol. 41; pp. 31 - 48
• Main Authors: Andrews, Lesley, Mutch, David G
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.05.2017
• Subjects: BRCA1; BRCA2; Breast Neoplasms; Female; Genes, BRCA2; Genetic Predisposition to Disease; Genetic Testing; hereditary ovarian cancer; Humans; Mutation; Obstetrics and Gynecology; Ovarian Neoplasms - genetics; Ovarian Neoplasms - prevention & control; Ovarian Neoplasms - surgery; Ovariectomy; Risk Assessment; risk-reducing salpingo-oophorectomy; BRCA1; BRCA2; hereditary ovarian cancer; risk reducing salpingo-oophorectomy; risk-reducing salpingo-oophorectomy
• ISSN: 1521-6934; 1532-1932
• DOI: 10.1016/j.bpobgyn.2016.10.017

Abstract Mutations in BRCA1 and BRCA2 account for the majority of families with hereditary breast and ovarian cancer syndrome, and account for 14% of epithelial ovarian cancer. Despite next generation sequencing, other identified genes (Lynch Syndrome, RAD51C , RAD51D and BRIP1 ) account for only a small proportion of cases. The risk of ovarian cancer by age 70 is around 40% for BRCA1 and 18% for BRCA2 . Most of these cancers are high grade serous cancers which predominantly arise in the fimbriae of the fallopian tube. Ovarian screening does not improve outcome, so women at high risk are recommended to undergo risk-reducing salpingo-oophorectomy around the age of 40, followed by HRT. Specimens should be carefully examined for occult malignancy. Mutation carriers may benefit from newly developed PARP inhibitors. Genetic testing should only be done after careful counseling, particularly if testing involves testing of panels of genes which may identify unsuspected disease pre-disposition or confusing variants of uncertain significance.