Voices

13  Mar  14

SGO Position Statement: Genetic Testing for Gynecologic Cancer

October 2014

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.

Background

Ovarian Cancer

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.

Endometrial cancer

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.

Voices

13  Mar  14

SGO Clinical Practice Statement: Genetic Testing for Ovarian Cancer

October 2014

Women diagnosed with epithelial ovarian, tubal, and peritoneal cancers should receive genetic counseling and be offered genetic testing, even in the absence of a family history.

Germline BRCA1 and BRCA2 mutations account for approximately 15% of invasive ovarian carcinomas, and a somewhat higher proportion of fallopian tube or peritoneal carcinomas [1,2,3]. In contrast, borderline ovarian neoplasms are not associated with mutations in BRCA1 and BRCA2 [4]. BRCA1 and BRCA2 mutations lead to a 15-50% lifetime risk of ovarian carcinoma, with an increased risk and earlier onset associated with BRCA1 compared to BRCA2 mutations. A number of other genes have also been shown to cause hereditary ovarian carcinoma.

Nearly one-third of women with hereditary ovarian carcinoma have no close relatives with cancer, and 35% of women with hereditary ovarian carcinoma are older than 60 years at diagnosis. Therefore, all women diagnosed with ovarian, fallopian tube or peritoneal carcinoma, regardless of age or family history, should receive genetic counseling and be offered genetic testing. Careful pre- and post-test counseling is essential to understanding genetic testing options and results. Genetic counseling and testing can be conducted by genetic counselors, as well as other knowledgeable medical professionals.

Identification of hereditary cancer susceptibility allows for identification of cancer risk in other organs. Additionally, genetic results are valuable to inform other family members about their cancer risk, allowing personalized prevention to high risk individuals, including more intensive screening and risk-reducing surgery. Family members found not to carry the mutation may also receive reassurance and avoid unnecessary screening and interventions. New therapies such as PARP inhibitors are currently being tested for the treatment of ovarian carcinoma associated with mutations in BRCA1 and BRCA2 [5]. The Society of Gynecologic Oncology (SGO) encourages the medical community to offer genetic counseling and testing to all women with ovarian, fallopian tube and peritoneal carcinoma.

References

[1]        Pal T, Permuth-Wey J, Betts JA, Krischer JP, Fiorica J, Arango H, et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer 2005;104:2807–16.

[2]        Schrader KA, Hurlburt J, Kalloger WE, Hansford S, Young S, Huntsman DG, et al. Germline BRCA1 and BRCA2 mutations in ovarian cancer. Obstet Gyncol 2012;120:235-240.

[3]        Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci USA 2011;108:18032-18037.

[4]        Romero I, Sun CC, Wong, KK, Bast RC, Gershenson DM. Low grade serous carcinoma: new concepts and emerging therapies. Gynecol Oncol 2013;130:660-666.

[5]        Kaye SB, Lubinski J, Matulonis U, Ang JE, Gourley C, Karlan BY, et al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J Clin Oncol 2012; 30(4):372–9.

Voices

13  Jun  13 dee-sparacio-blog category Dee Sparacio

To Test or Not to Test | Dee Sparacio

Recently Angelina Jolie was in the news, not for her latest movie, but for having a preventative mastectomy to reduce her risk of developing breast cancer.  Angelina had genetic testing done and had learned she carried the BRCA1 & 2 mutations. The mutations placed her at a higher risk for breast and ovarian cancer than the average women.  Jolie’s mother had passed away at the age of 56 due to ovarian cancer.

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