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 four 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.
Original languageEnglish
JournalFamilial Cancer
Publication statusAccepted/In press - 3 Mar 2021


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