Moderate-risk variants in hereditary breast and ovarian cancer: seven-year experience from a specialized center.

ATM, BARD1, CHEK2, RAD51C, RAD51D

Pathogenic or likely pathogenic variants in moderate-risk genes: ATM, BARD1, CHEK2, RAD51C, RAD51D

This retrospective study analyses seven years (2018-2024) of germline testing in 3,416 individuals evaluated at the Erlangen HBOC centre, focusing on the moderate-risk genes ATM, BARD1, CHEK2, RAD51C and RAD51D, classified according to ACMG/IARC criteria. CHEK2 was the most frequently altered moderate-risk gene, followed by ATM, whereas pathogenic variants in BARD1, RAD51C and RAD51D were observed only in predictive testing or in individuals with breast malignancies. Most women with moderate-risk variants were enrolled in the intensified breast cancer surveillance programme, except in justified cases based on individual risk factors. An isolated moderate-risk variant generally did not warrant risk-reducing breast surgery, whereas risk-reducing salpingo-oophorectomy was primarily discussed for RAD51C and RAD51D, with individualised adjustments for complex genotypes carrying several pathogenic variants.

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

A snapshot of practice in an expert centre, consistent with current doctrine: intensified breast surveillance rather than surgery for an isolated moderate-risk variant, salpingo-oophorectomy discussed for RAD51C/RAD51D. The abstract quantifies neither the number of carriers per gene nor adherence to recommendations, which limits the scope of the conclusions. Complex genotypes with several variants would need cumulative risk data, which are absent here.

Analysis by Dr Thibaut Benquey