Extended gene panel testing in lobular breast cancer.

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Lobular breast cancer (LBC) constitutes approximately 15% of all breast cancer cases.
• Understanding the genetic underpinnings of LBC is crucial for risk assessment and targeted therapies.

Purpose of the Study:

• To investigate the frequency of pathogenic germline variants (PGVs) in an expanded panel of genes among women diagnosed with LBC.
• To identify specific genes associated with an increased risk of developing LBC.

Main Methods:

• A cohort of 302 women with LBC and 1567 controls were initially screened for BRCA1/2 PGVs.
• A subset of 134 LBC patients negative for BRCA1/2 PGVs underwent extended genetic screening.
• The extended panel included genes such as ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.

Main Results:

• Pathogenic germline variants (PGVs) were detected in 11.59% of LBC patients.
• BRCA1/2 PGVs were found in 7.28% of LBC patients, while other actionable PGVs were identified in 7.46%.
• Significantly increased LBC risk was associated with PGVs in BRCA1 (OR=13.17), BRCA2 (OR=10.33), and ATM (OR=8.01).

Conclusions:

• Extended genetic panel testing is beneficial for LBC patients, revealing a high rate of actionable PGVs.
• Pathogenic variants in ATM show a previously unrecognized association with an increased risk of lobular breast cancer.
• The findings support comprehensive genetic screening for LBC to improve risk stratification.