Germline ATM Testing in Hereditary Cancer Syndromes: Feedback from a Five-Year Center Cohort.

ATM

Heterozygous germline pathogenic or likely pathogenic ATM variants, a gene of the double-strand break response

The authors retrospectively reanalysed ATM in 1,707 probands tested between 2019 and 2025 on hereditary breast and ovarian cancer (HBOC) or pancreatic cancer panels in a single centre. Targeted reanalysis identified 33 additional probands with pathogenic or likely pathogenic variants, raising diagnostic yield from 7.3% to 9.1% in HBOC and from 4.3% to 9.7% in pancreatic cancer. Among the 22 breast cancer probands, mean age at diagnosis was 47 years. Case-control comparison yielded an odds ratio of 3.85 (95% CI 2.43-6.08; p = 8.5 × 10⁻⁹) for breast cancer and 15.81 (95% CI 6.31-39.66; p = 4.0 × 10⁻⁹) for pancreatic cancer. The authors argue for including ATM in French national hereditary cancer panel recommendations, with appropriate surveillance and counselling.

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

The number that matters here is the doubling of diagnostic yield in the pancreatic setting, achieved by reanalysing already generated data: the practical message concerns periodic reinterpretation more than the scope of the test itself. The odds ratio of 15.81 for pancreatic cancer rests on very few carriers with a wide confidence interval (6.31-39.66) and comes from a single-centre series selected on testing criteria: read it as a directional signal, not as a risk figure usable at face value in clinic. For breast cancer, an OR around 4 is consistent with published estimates and does not change management, which remains enhanced surveillance without an indication for prophylactic surgery.

Analysis by Dr Thibaut Benquey