Genetic profiling of healthy family members of breast and ovarian cancer patients in Estonia.

Pathogenic variants across 23 predisposition genes, mostly BRCA1 and BRCA2, identified in healthy relatives of affected patients.

This retrospective analysis covers 3,472 healthy family members of breast or ovarian cancer patients tested in routine clinical practice in Estonia. The population was predominantly female (87.6%), with a mean age of 41.1 ± 13.0 years, and 78.6% were younger than 51, the usual age for starting standard screening. A pathogenic variant was identified in 683 individuals (19.7%): 41.8% among relatives tested when a familial variant was known (n = 1,009) versus 8.0% when no familial variant was known (n = 2,408). Men were more often tested when the familial variant was known (26.6% versus 6.6%), and 34.0% of tested men were carriers. Variants involved 23 different genes, with BRCA1 and BRCA2 accounting for 58.4% of them, followed by ATM, BRIP1, CHEK2 and PALB2.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The figure to remember is the 8% yield among relatives tested without an identified familial variant: cascade testing in the strict sense is not enough, and a substantial share of carriers is detected outside that framework. The second lesson is age: nearly 80% of tested relatives were under 51, hence identifiable before entering population screening, which is where prevention has the most value. A descriptive, single-country study with no follow-up or clinical outcome data, but useful for sizing a relative-testing programme.

Analysis by Dr Thibaut Benquey