Genetic Testing for Gynecologic Cancer
Ovarian cancer: Women diagnosed with epithelial ovarian, fallopian tube, and peritoneal cancers should receive genetic counseling and be offered genetic testing. Women who do not have gynecologic cancer but have a close family member (such as a mother, sister, or daughter) diagnosed with ovarian, fallopian tube, or primary peritoneal cancer or who have a family history of ovarian and breast cancer in several relatives should also receive genetic counseling.
Endometrial cancer: All women diagnosed with endometrial cancer should be assessed for Lynch syndrome. In addition, women with a family history of endometrial and colon cancer should pursue genetic counseling, regardless of whether they have been diagnosed with cancer.
Rapidly changing testing technologies: The increased complexity of testing options and genetic results make detailed, individualized patient counseling by a knowledgeable provider an essential part of the testing process. Genetic counselors may be particularly helpful in this process.
Inherited mutations or abnormalities are present from birth in the genes of every cell of the body. Genes are the building blocks of all cells. They are passed down from either parent and may, in turn, be passed on to children. Inherited BRCA1 and BRCA2 mutations account for approximately 15 percent of ovarian cancer. These mutations lead to a 15 to 50 percent lifetime risk of developing ovarian, fallopian tube, or peritoneal cancer. Many other gene mutations are associated with increased risk for ovarian cancer. Some of these include MSH2, MLH1, MSH6, PMS2, EPCAM, BRIP1, RAD51D, RAD51C, PALB2, BARD1, and TP53. Current estimates are that 20 to 25 percent of women with ovarian, fallopian tube, or peritoneal cancer may carry an inherited mutation in one of these genes.
Women who are unaffected by gynecologic cancer but who have a close family member (such as a mother, sister, or daughter) diagnosed with ovarian, fallopian tube, or peritoneal cancer or who have a family history of ovarian and breast cancer in several relatives should also undergo genetic counseling.
Approximately 3 to 5 percent of endometrial cancers are due to Lynch syndrome, which is caused by inherited mutations in one of five genes: MLH1, MSH2, MSH6, PMS2, or EPCAM. Patients with Lynch syndrome have a 40 to 60 percent lifetime risk for endometrial and colon cancer, as well as an increased risk for ovarian cancer. Relying on the family history of cancer alone does not identify all women with Lynch syndrome. In order to better identify Lynch syndrome, broad screening or assessment of endometrial and colon tumors for Lynch syndrome is recommended.
All women who are diagnosed with endometrial cancer should undergo some type of systematic assessment for Lynch syndrome, which would include a detailed family history of cancer and possible specific tests on the cancer tissue. In addition, women with a family history of endometrial and colon cancer should receive genetic counseling, regardless of whether they have been diagnosed with cancer.
Rapidly changing testing technologies
Next generation sequencing is a tool that allows inexpensive, rapid DNA sequencing, which is having a major impact on both cancer research and clinical care. Cancer gene panels use next generation sequencing technology to assess inherited mutations in multiple genes simultaneously. These first reached the clinical marketplace in late 2011. The unanimous decision by the U.S. Supreme Court in June 2013 invalidated human gene patents, leading to a rapid expansion of clinical options for genetic testing. Current cancer gene panels vary in size from just two genes (i.e., BRCA1 and BRCA2) to larger panels that include more than 50 genes.
Advantages of cancer gene panels include decreased cost and improved efficiency of cancer genetic testing by reducing the time involved, number of patient visits, and number of tests sent. The major drawback of cancer gene panels is the increased complexity of the results. While we have clear guidelines for managing cancer risk in the setting of BRCA1 and BRCA2 mutations and Lynch syndrome, for many other genes recommendations for mutation carriers are not established. Involvement of a cancer genetics professional is important to help order the most appropriate genetic test and to interpret the results.