Current Indication Criteria for Testing Mutations in BRCA1 and BRCA2 Genes in Breast and Ovarian Cancer

Indication Criteria for Testing in Sporadic Forms

Suspicion of a sporadic form of BRCA-positive carcinoma is considered, and genetic testing is performed in the following cases:

• Ovarian/fallopian tube cancer or primary peritoneal carcinoma at any age.
• Triple-negative breast cancer (TNBC) up to 60 years of age (note: medullary breast carcinomas almost always coincide with TNBC).
• Unilateral breast cancer up to 45 years (up to 50 years with unknown family history).
• Two separate primary breast cancers (first one up to 50 years, or both up to 60 years).
• Duplication of breast and pancreatic cancer at any age.
• Male breast cancer at any age.

Indication Criteria for Testing in Familial Forms

It holds that ovarian, fallopian tube, or primary peritoneal cancer in family history is always an indication for testing. Testing is also indicated in the following cases of the occurrence of relevant cancers in relatives:

• 3 relatives – at least 3 relatives (including the proband) with breast cancer at any age.
• 2 relatives (including the proband) with breast cancer, where at least 1 is diagnosed up to 50 years of age or both up to 60 years.
• Proband with breast cancer at any age and a direct relative with ovarian cancer, triple-negative breast cancer, or medullary breast cancer, male breast cancer, pancreatic cancer, or high-grade or primarily metastatic prostate cancer.

If a somatic, pathogenic, or likely pathogenic mutation is found in genes associated with hereditary breast and ovarian cancer in the tumor (whether breast, ovarian, or another type of tumor), it is also an indication for testing familial forms.

Predictive testing of a known family mutation is performed on relatives from 18 years of age; in special cases, an individual approach is possible.

Testing for Treatment Purposes

Knowledge of the BRCA1/2 gene status can serve as an indication of the suitability of surgical treatment or the decision on appropriate chemotherapy (inclusion of platinum derivatives in patients with triple-negative breast cancer). The BRCA1/2 status can also serve for the potential inclusion of a patient in treatment with PARP inhibitors (e.g., in high-grade epithelial ovarian tumors or metastatic breast cancer).

If a patient is already ill and does not fall into one of the groups listed above at risk of hereditary cancer, current recommendations published in the 2019 supplement of Klinická onkologie state that outside of populations at hereditary risk, other indications for treatment are determined by the attending physician considering the rapidly developing possibilities of new treatment procedures.

When deciding on treatment, it is good to remember the possibility of determining somatic mutations in tumor tissue. This examination captures both types of mutations – germline and purely somatic. If a patient at hereditary risk is initially tested for the presence of somatic mutations, they should always be referred for genetic testing for family prevention, regardless of both positive and negative results.

In cases where the oncologist or gynecologist urgently refers the patient for genetic consultation and testing to obtain data for therapeutic decision-making, they should always indicate how quickly the test result is needed.

Given the rapidly expanding possibilities of new treatment procedures, the indication for testing mutations in the BRCA1/2 genes is in the hands of the attending physician.

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Source: BRCA-related breast and/or ovarian cancer syndrome. NCCN Guidelines, version 3.2019. Available at: www2.tri-kobe.org/nccn/guideline/gynecological/english/genetic_familial.pdf