Key Points
- It is estimated that there will be 22,530 new cases of ovarian cancer diagnosed in 2019 in the United States and, in spite of advances in treatment, an estimated 13,980 women will die from the disease.
- Ovarian cancer ranks fifth in cancer deaths among women.
- Approximately 25% of all ovarian cancers are caused by a heritable genetic condition.
- Many medical societies recommend genetic testing for all women diagnosed with ovarian cancer, yet only about 30% of women undergo any genetic testing.
Diagnosis
Recommendation 1.1
- All women diagnosed with epithelial ovarian cancer should be offered germline genetic testing for BRCA1, BRCA2 and other ovarian cancer susceptibility genes, irrespective of their clinical features or family cancer history. Somatic tumor testing for BRCA1 and BRCA2 pathogenic or likely pathogenic variants should be performed in women who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant. (Strong Recommendation; EB-B-I)
Recommendation 1.2
- Women diagnosed with clear cell, endometrioid or mucinous ovarian cancer should be offered somatic tumor testing for mismatch repair deficiency (dMMR). (Moderate Recommendation; EB-B-I)
Recommendation 1.3
- Testing for dMMR may be offered to women diagnosed with other histological types of epithelial ovarian cancer. (Moderate Recommendation; EB-B-I)
Recommendation 1.4
- Those genetic evaluations should be conducted in conjunction with health care providers, including genetic counselors, familiar with the diagnosis and management of hereditary cancer syndromes, to determine the most appropriate testing strategy and discuss implications of the findings, positive or negative, for first- or second-degree blood relatives. (Moderate Recommendation; IC-L)
Recommendation 1.5
- First- or second-degree blood relatives of an ovarian cancer patient with a known germline pathogenic cancer susceptibility gene mutation or variant should be offered individualized genetic risk evaluation, counselling and genetic testing. (Strong Recommendation; EB-B-H)
Recommendation 2.1
- Women diagnosed with epithelial ovarian cancer with identified germline or somatic pathogenic or likely pathogenic variants in BRCA1 and BRCA2 genes should be offered treatments that are FDA-approved under their labeled indication in the upfront and the recurrent setting. BRCA1/2 pathogenic or likely pathogenic variants qualify for and have been associated with higher rates of response to FDA-approved treatments such as PARP inhibitors. (Strong Recommendation; EB-B-H)
Recommendation 2.2
- Women diagnosed with recurrent epithelial ovarian cancer with identified dMMR should be offered FDA-approved treatment under their labeled indication based on these results. dMMR qualifies for FDA-approved treatment. (Moderate Recommendation; EB-B-I)
Recommendation 2.3
- No recommendations can be made supporting routine tumor testing using currently available homologous recombination deficiency (HRD) assays. Current assays evaluating HRD have been applied to stratify women with ovarian cancer for treatment. (No recommendation; L)
Recommendation 2.4
- Clinical decisions should not be based on a variant of uncertain significance (VUS). Care providers and patients and family members tested should be aware that reclassification of VUS is an ongoing process, and it may eventually become possible to definitively determine if a variant is deleterious or benign. Until that time, the patient’s clinical features and family history should inform clinical decision-making. (Strong Recommendation; EB-B-H)
Recommendation 3.1
- Women with epithelial ovarian cancer should be offered testing, as outlined in 1.1, at the time of diagnosis. This has implications for therapeutic decision making. (Strong Recommendation; EB-B-H)
Recommendation 3.2
- Women with epithelial ovarian cancer who have not had germline testing at the time of diagnosis should be offered germline genetic testing as soon as feasibly possible, as outlined in 1.1. In women who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant, somatic tumor testing for BRCA1 and BRCA2 pathogenic or likely pathogenic variants should be offered. Somatic tumor testing for BRCA1 and BRCA2 pathogenic or likely pathogenic variants may be reserved for time of recurrence for women who have completed upfront therapy and are currently in observation, as presence of these mutations qualify the patient for FDA-approved treatments. (Moderate Recommendation; EB-B-I)
Table 1. Definition of Terms
| Term | Description |
|---|---|
| Genetic variant | An alteration in the most common DNA nucleotide sequence. The term variant can be used to describe an alteration that may be benign, pathogenic, or of unknown significance. The term variant is increasingly being used in place of the term mutation. |
| Germline variant | A gene change in a reproductive cell (egg or sperm) that becomes incorporated into the DNA of every cell in the body of the offspring. A variant contained within the germline can be passed from parent to offspring and is, therefore, hereditary. |
| Somatic variant | An alteration in DNA that occurs after conception and is not present within the germline. Somatic variants can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. Somatic variants can (but do not always) cause cancer or other diseases. |
| Actionable genetic information | The presence or absence of a genetic variant in a tumor or the germline that can be used to inform clinical management. (Adapted from Dancey et al. (Dancey JE, Bedard PL, Onetto N, et al.: The genetic basis for cancer treatment decisions. Cell 148 (3): 409-20, 2012.) |
| Pathogenic | Directly contributes to the development of disease. Additional evidence is not expected to alter the classification of this variant. [Note: Not all pathogenic variants are fully penetrant.] |
| Likely pathogenic | Very likely to contribute to the development of disease, but scientific evidence is currently insufficient to prove this conclusively. |
| Uncertain significance | There is not enough information at this time to support a more definitive classification of this variant. |
| Likely benign | Not expected to have a major effect on disease, but the scientific evidence is currently insufficient to prove this conclusively. |
| Benign | Does not cause disease. Additional evidence is not expected to alter classification of this variant. |
