A central tenet of a recently issued American Society of Clinical Oncology (ASCO) guideline is that all women with a diagnosis of epithelial ovarian cancer should be offered testing for specific germline mutations associated with increased ovarian cancer susceptibility. This ASCO guideline has been published in the Journal of Clinical Oncology.
It has been estimated that approximately 25% of ovarian cancers are associated with underlying pathogenic mutations in heritable genes (ie, germline mutations), such as BRCA1, BRCA2, as well as genes associated with homologous recombination and the Fanconi anemia pathway.
Furthermore, detection of 1 or more of these germline mutations in patients with ovarian cancer can reveal prognostic information, potentially facilitate selection of optimal therapeutic approaches, and have implications for family members of the patient. Detection of particular pathogenic tumor-only mutations (ie, somatic mutations), occurring in BRCA1/2 genes and genes associated with mismatch repair deficiency (dMMR) can also provide prognostic and predictive information in the setting of epithelial ovarian cancer.
Beyond offering testing for deleterious germline mutations in BRCA1/2 — as well as other genes shown to increase susceptibility to ovarian cancer — to all women with epithelial ovarian cancer at the time of disease diagnosis, some of the other key recommendations made by the ASCO Expert Panel were:
- All women with a diagnosis of epithelial ovarian cancer not characterized by a pathogenic/potentially pathogenic germline mutation in BRCA1/2 should be offered testing to detect the presence of pathogenic/potentially pathogenic somatic BRCA1/2 mutations
- All patients with disease characterized by clear cell, endometrioid, and mucinous histology should be offered testing for somatic mutations in genes associated with dMMR, and such testing may also be offered to those with other histologic subtypes of epithelial ovarian cancer
- Both pre- and posttest genetic counseling should be provided to patients, and a genetic counselor should be involved in the interpretation of the results of genetic/genomic testing and the communication of these results to patients
- Gene variants of unknown significance (ie, not identified as pathogenic, potentially pathogenic, or benign) should not be used to direct clinical decision making
- An individualized assessment of genetic risk should be offered to first- or second-degree relatives of patients with epithelial ovarian cancer characterized by a pathogenic germline mutation known to increase risk of ovarian cancer
- US Food and Drug Administration (FDA)-approved BRCA1/2-directed therapy should be offered to patients with epithelial ovarian cancer associated with a pathogenic/potentially pathogenic BRCA1/2 germline or somatic mutation, according to indications specified in the product label
Konstantinopoulos PA, Norquist B, Lacchetti C, et al. Germline and somatic tumor testing in epithelial ovarian cancer: ASCO Guideline [published online January 27, 2020]. J Clin Oncol. doi: 10.1200/JCO.19.02960