SCIENTIFIC BACKGROUND

BRCA1, BRCA2

Scientific Background

With a share of approximately 30% of all cancers, breast cancer is by far the most common tumor in women in Europe. Ovarian cancer accounts for 3.3% of all new cancer cases in female patients. It is estimated that 5-10% of all breast cancers and 10-25% of ovarian cancers are hereditary. The characteristic features of hereditary breast and ovarian cancer are an early age of onset of the disease and/or a high incidence in the family. Genetic diagnosis is recommended if one of the following criteria is met in one patient or in a family:

 

  • high incidence of breast OR ovarian cancer in the family (2 or more women)
  • breast cancer at a young age (<50 years)
  • incidence of breast AND ovarian cancer in the family

 

Pathogenic variants in the BRCA1 or BRCA2 genes can be detected in about 24% of women or families to whom one of the above criteria applies. Pathogenic changes in one of the genes significantly increase the risk of breast and ovarian cancer, but are also associated with a slightly increased risk of other cancers, e.g., pancreatic, prostate and male breast cancer. Carriers are recommended to undergo more intensive screening medical check-ups and, if necessary, preventive measures (e.g., prophylactic mastectomy). The benefits and risks of radiotherapy should be considered in the case of ill patients, as there is an increased risk of secondary carcinomas in the radiation field.

 

Several studies have consistently shown that the prevalence of pathogenic variants in BRCA1/2 in <50-year-old patients with triple-negative breast cancer is (significantly) more than 10%, regardless of the family constellation. Therefore, genetic counselling is also recommended in these cases.

 

Recent studies on patients with sporadic, platinum-sensitive ovarian cancer (without a conspicuous family history, also independent of the age of onset of the disease) were able to prove pathogenic germline variants in BRCA1/2 in an average of 20.8% of patients. After examination of other risk genes, the prevalence increased to >25%. This group of patients should therefore also be made aware of the risk of hereditary disease. In the case of a family history of Lynch syndrome, the possibility of genetic diagnosis should also be examined.

 

References

Rebbeck et al. 2018, Hum Mutat 39:593 / Engel et al. 2018, BMC Cancer 18:562 / Schmutzler 2017, Geburtsh Frauenheilk 77:733 / Harter et al. 2017, PLoS One 12:e0186043 / Hahnen et al. 2017, Breast Care (Basel) 12:15 / Kast et al. 2016, J Med Genet 53:465 / Leitlinienprogramm Onkologie: S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms, Version 4.1, 2018 / Leitlinienprogramm Onkologie: S3-Leitlinie Diagnostik, Therapie und Nachsorge maligner Ovarialtumoren, Langversion 3.0, 2019

 

 

Genes in bold are recommended by International guidelines, including German expert panels and/or have been more often associated with specific cancers.

GENES

BRCA1, BRCA2
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