Germline Multigene Panel Testing in Women With Invasive Lobular Cancer.

Germline pathogenic variants in breast cancer predisposition genes

Invasive lobular carcinoma (ILC) is the second most common histologic breast cancer subtype, with poorly defined genetic predisposition. This prospective study at the European Institute of Oncology (Milan, 2022-2025) tested 414 women with ILC using a 113-gene panel. Pathogenic variants were identified in 46 patients (11.1%), including 20 (4.8%) in moderate- to high-risk genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, FANCM, PALB2, RAD51C, RAD51D, STK11, TP53, PTEN). Carriers of these variants had significantly reduced 5-year breast-cancer-free survival (62.2% vs 92.1%; HR 3.91). Polygenic risk scores showed no prognostic value in this setting.

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

Identifying a subgroup of carriers at risk of early relapse can refine genetic counselling and inform surveillance and therapeutic strategies in ILC. The lack of prognostic value of polygenic risk scores here is a reminder that they do not transfer mechanically across histologic subtypes. The broad 113-gene panel nonetheless remains a source of VUS whose clinical management is difficult.

Analysis by Dr Thibaut Benquey