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Updated: Nov 11, 2025
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Extended gene panel testing in lobular breast cancer
Elke M van Veen1,2, D Gareth Evans3,4,5,6, Elaine F Harkness7,8
1Manchester Centre for Genomic Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Purpose:
Lobular breast cancer (LBC) accounts for ~ 15% of breast cancer. Here, we studied the frequency of pathogenic germline variants (PGVs) in an extended panel of genes in women affected with LBC.
Methods:
302 women with LBC and 1567 without breast cancer were tested for BRCA1/2 PGVs. A subset of 134 LBC affected women who tested negative for BRCA1/2 PGVs underwent extended screening, including: ATM, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, RAD51D, and TP53.
Results:
35 PGVs were identified in the group with LBC, of which 22 were in BRCA1/2. Ten actionable PGVs were identified in additional genes (ATM(4), CDH1(1), CHEK2(1), PALB2(2) and TP53(2)). Overall, PGVs in three genes conferred a significant increased risk for LBC. Odds ratios (ORs) were: BRCA1: OR = 13.17 (95%CI 2.83-66.38; P = 0.0017), BRCA2: OR = 10.33 (95%CI 4.58-23.95; P < 0.0001); and ATM: OR = 8.01 (95%CI 2.52-29.92; P = 0.0053). We did not detect an increased risk of LBC for PALB2, CDH1 or CHEK2.
Conclusion:
The overall PGV detection rate was 11.59%, with similar rates of BRCA1/2 (7.28%) PGVs as for other actionable PGVs (7.46%), indicating a benefit for extended panel genetic testing in LBC. We also report a previously unrecognised association of pathogenic variants in ATM with LBC.
