BRCA2 and genetic mutations in prostate cancer: an updated practical guide on “when and how” testing across international guidelines

prostate cancer (pCa) is the second most common cancer in men, with an estimated 375,000 deaths globally in 2020 and an estimat ed increase in burden by 2040 from 1.4 million (2020) to 2.9 million (2040).1 established risk factors include age, african american ancestry,2 and a family history of pCa, which increases risk two- to three-fold, suggesting a genetic predis position. genetic variants are particularly im portant in the development of pCa in younger patients, thus distinguishing between hereditary and familial forms is key for accurate diagnosis and prognosis.3 hereditary cases, which make up 5-10% of all cases, are caused by inherited ge netic variants, while familial cases, comprising 15-20% of cases, occur due to a family history without detectable genetic mutations, influenced by environmental factors and aging. additional ly, having an affected brother increases the likeli hood of developing pCa more than having an af fected father.4 hereditary prostate cancer (hpCa) is suspected when there is a family history across three generations, or at least three first-degree relatives with pCa, or at least two relatives di agnosed before age 55 and may include cases of other cancers.5 hpCa is caused by autosomal dominant gene mutations and is associated with early onset, aggressive progression, advanced stages, and a higher recurrence after surgery compared to sporadic cases.6 genetic testing for hereditary cancer is important for determining treatment options and access to novel therapies. different clinical guidelines have varying rec ommendations regarding when and how to test for BrCa2 mutations in pCa, with most empha sizing targeted genetic testing for specific patient populations. We provide an overview of screen ing and diagnostic recommendation for genetic testing and particularly BrCa2 testing across different guidelines.