Frequency of germline pathogenic variants in breast cancer predisposing genes in a national cohort of young women with breast cancer

Frequency of germline pathogenic variants in 18 breast cancer predisposition genes in women diagnosed at ≤40 years

This Canadian national cohort (805 women with breast cancer diagnosed at age 40 or younger, 33 centres) tested for pathogenic variants in 18 predisposition genes. The positivity rate was 18.6%, of which 63% in BRCA1 or BRCA2, and 6.8% in a gene other than BRCA1/2 (CHEK2, ATM, PALB2, TP53...). Frequencies were higher in lobular (29.2%), triple-negative (27.5%) and bilateral (35.7%) tumors. The authors conclude that genetic testing should be offered to all women diagnosed at age 40 or younger.

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

Solid data supporting systematic germline testing in young women with breast cancer, an 18.6% positivity rate being clearly above usual indication thresholds. The fact that nearly 7% of variants are outside BRCA1/2 argues for broad analysis — a multigene panel, or upfront an exome/genome approach that captures these genes without a priori selection. This is exactly the kind of cohort that supports mainstreaming testing in oncology consultations.