Epithelial ovarian cancer is an important female cancer in Singapore and represents an increasing incidence over the last 3 decades, but stabilizing from 1998 to 2002.

It is the 4 th most common female cancer. The lifetime risk for ovarian cancer is about 1 to 2%. Most ovarian cancers do not occur in familial patterns and are termed sporadic. However, some families present with several individuals having ovarian cancer, sometimes with breast cancer as well. Such families may carry a highly penetrant germline genetic mutation related to BRCA1 or BRCA2.

The lifetime risk for breast cancer in mutation carriers is as high as 80% for breast cancer (both BRCA1 and BRCA2) whereas for ovarian cancer, BRCA1 mutation carriers have a higher lifetime risk (40%) than BRCA2 carriers (20%).

Other familial cancers predisposing to ovarian cancer could also include hereditary nonpolyposis colon cancer but this article will focus on BRCA1 and BRCA2 genes only.

Ovarian cancers related to BRCA1 and BRCA2 are usually papillary serous type although other subtypes have been reported. Reports of fallopian tubes and peritoneum cancers occur with increased frequency. However, borderline ovarian tumours do not seem to be part of the predisposition syndrome.

The outcome for ovarian cancer treatment may be better for mutation carriers. Although BRCA1 families are associated with only breast and ovarian cancer, BRCA2 families may also have male breast cancer, prostate, pancreas, melanoma and other cancers.

The two genes are large and mutations are scattered throughout the genes. However for BRCA2, there is an ovarian cancer cluster region in the central part of the gene associated with a higher risk for ovarian cancer. These mutations are not alien to Singapore. NCC surgical oncologist, Dr Ho G H's group was one of the first to report BRCA1 mutations in Singapore. A founder mutation related to ethnicity was first reported in Singapore for the Malay population at BRCA1 2846insA by Dr Ann Lee's lab in NCC.

Genetic testing is available following genetic counselling for women in breast and ovarian cancer families. There are limits of genetic testing and the issues, pros and cons are best discussed with a cancer genetics-counselling centre.

Screening for ovarian cancer for mutation carriers is limited. The use of oral contraceptives among mutation carriers is associated with a reduced risk for ovarian cancer, but there is some concern that a modest increase in breast cancer risk may occur.

There is more data recently that prophylactic oophorectomy may be useful for mutation carriers. The risk for breast cancer can be lowered by nearly 50% and ovarian cancer risk by 90% with prophylactic salpingo-oophorectomy. Mutation carriers, particularly if they have completed their families above the age of 35 years, could consider this.

 

Peter Ang
Consultant
Medical Oncology
National Cancer Centre, Singapore