The International Federation of Gynecology and Obstetrics (FIGO) Gynecologic Oncology Section has prepared this article to assist healthcare professionals in the recognition, identification, and diagnosis of gynecologic oncology. The guidelines were prepared after extensive consultation with the committee and the FIGO Executive Board, which also indicates that this article is an expert consensus.
In the early 1990s, the molecular etiology of several hereditary tumors was discovered. The discovery of specific genes associated with some cancers has allowed clinicians to more accurately assess the risk of developing hereditary tumors and to take appropriate screening and preventive measures.
Two of the best examples in gynecologic tumors are the discovery of the BRCA1 and BRCA2 genes and the molecular mechanisms of Lynch syndrome. The following section describes the diagnosis, screening and treatment of each type of syndrome.
1. Hereditary breast cancer-ovarian cancer syndrome
Hereditary breast-ovarian cancer syndrome occurs in most families because of germline mutations in the BRCA1 and BRCA2 genes. Although the reported incidence varies widely, generally about 10% of ovarian cancer cases and 3-5% of breast cancer cases occur due to mutations in the BRCA1 or BRCA2 genes.
However, a recent Australian study reported that 14% of over 1,000 ovarian cancers screened had mutations and 23% were low-grade malignant plasma cancers.
It is estimated that 1 in 800 to 1 in 300 of the total population has a BRCA1 or BRCA2 mutation. 39%-46% of women with a BRCA1 mutation have a risk of ovarian cancer, compared to 12%-27% with a BRCA2 mutation.
The lifetime risk of breast cancer in women with BRCA1 or BRCA2 mutations is 65%-74%, and the 10-year risk of secondary ovarian cancer in women with BRCA1 and BRCA2 mutations is 12.7% and 6.8%, respectively.
Ovarian cancers with mutations in the BRCA1 or BRCA2 genes have a well-defined histological phenotype, are predominantly plasmacytosis and endometriosis, and are highly differentiated and low-grade malignant. This did not contain mucinous carcinomas or junctional tumors. Primary tubal and primary peritoneal carcinomas are also associated with mutations in the BRCA1 or BRCA2 genes.
Specific screening and prevention strategies can identify high-risk groups and thereby reduce the incidence and mortality of breast and ovarian cancers. Clinical criteria have been developed to assess and identify populations with a genetic predisposition for breast or ovarian cancer greater than 20-25% (Box 1). Genetic risk analysis is strongly recommended for this group.
A second set of clinical criteria was developed to assess populations with a genetic predisposition to breast or ovarian cancer greater than 5%-10% and for whom genetic risk analysis may be valid (Box 2). However, it should be noted that these recommendations are not universal and that this distinction is not reflected in the setting criteria, especially for Germany and Australia.
Populations with a genetic predisposition to breast and ovarian cancer greater than 20-25% and for whom genetic risk analysis is recommended.
Female patients with a history of both breast and ovarian cancera.
Patients with ovarian cancer who have a first-degree relative with ovarian cancer or premenopausal breast cancer or both
Female patients under 50 years of age with breast cancer whose next of kin have ovarian cancera or next of kin male with breast cancer at any age.
Patients of German-Jewish ancestry with ovarian cancer.
Female breast cancer patients of German-Jewish ancestry who are younger than 40 years of age at the time of diagnosis.
Women with low-grade malignant plasmacytoma, primary peritoneal carcinoma or primary fallopian tube carcinoma.
Women with a known close relative with a mutation in the BRCA1 or BRCA2 gene.
Women with a family history of indications for Lynch syndrome (hereditary non-polyposis colorectal cancer), such as colon cancer, especially if diagnosed before age 50, or endometrial, ovarian, gastric or urologic tumors.
Peritoneal and fallopian tube cancers are also part of the hereditary breast-ovarian frame syndrome.
Box 1 Guidelines for genetic risk analysis for hereditary breast and ovarian cancer (genetic predisposition >20-25%)
A growing body of data indicates that the rate of BRCA1 or BRCA2 gene mutations in unscreened patients with a family history of these diseases is 16% and 22%, respectively, in patients diagnosed with low-grade malignant plasma ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, while 9% of patients without a family history of breast or ovarian cancer also have a BRCA1 or BRCA2 germline mutation.
Given these mutation rates, it is appropriate to consider genetic risk analysis for low-grade malignant plasma ovarian cancer, primary peritoneal cancer, or fallopian tube cancer, especially in patients whose analysis results may have implications for family members.
Triple-negative female breast cancer patients should also be included in the BRCA1 gene mutation testing population. A recent meta-analysis that included 12 studies indicated that the relative risk of BRCA1 gene mutation was 5.65 in triple-negative female breast cancer patients, significantly higher than in non-triple-negative female breast cancer patients. Additional guidelines are listed in Boxes 1 and 2.
Populations with a genetic predisposition to breast and ovarian cancer greater than 5-10% and highly considered for genetic risk analysis.
Women younger than 40 years of age at the time of breast cancer diagnosis
Patients of any age with cervical cancer, primary peritoneal cancer or highly differentiated plasmacytoma of the fallopian tubes
Women with bilateral breast cancer (especially those younger than 50 years of age at the time of the first diagnosis)
Women with breast cancer at age 50 or younger whose next of kin also had breast cancer at age 50 or younger, women of German-Jewish ancestry with breast cancer at age less than 50, women with breast cancer at any age and 2 or more of their next of kin who had breast cancer at any age (especially if at least 1 case was diagnosed at age 50 or younger) who were not affected by a next of kin meeting any of the previous criteria Women with triple negative breast cancer (ER/PR negative, HER2 negative)
Box 2 Guidelines for genetic risk analysis for hereditary breast and ovarian cancer (genetic predisposition >5-10%) Women with mutations in the BRCA1 or BRCA2 genes need to have a tubal oophorectomy (RRSO) at age 35 years or after delivery. Some countries recommend surgery at age 40 or 5 years before the youngest age of onset in the family. In bilateral RRSO all ovarian and fallopian tube tissue is removed. Pelvic irrigation should be performed to allow complete visualization of the peritoneal surface.
A complete case report should include serial sections of the ovaries and fallopian tubes spaced no more than 3 mm apart with microscopic findings of occult carcinoma, which is necessary. Patients should be informed that after RRSO they have approximately a 2-5% risk of occult cancer and a small risk of residual cancer from primary peritoneal cancer.