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. 2022 Apr;21(2):129-136.
doi: 10.1007/s10689-021-00241-5. Epub 2021 Mar 25.

Extended gene panel testing in lobular breast cancer

Elke M van Veen  1   2 , D Gareth Evans  3   4   5   6 , Elaine F Harkness  7   8 , Helen J Byers  1   2 , Jamie M Ellingford  1   2 , Emma R Woodward  1   2 , Naomi L Bowers  1 , Andrew J Wallace  1 , Sacha J Howell  7   9   10 , Anthony Howell  7   9 , Fiona Lalloo  1 , William G Newman  1   2 , Miriam J Smith  1   2
Affiliations

Extended gene panel testing in lobular breast cancer

Elke M van Veen et al. Fam Cancer. 2022 Apr.

Abstract

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.

Keywords: ATM; Genetics; Lobular breast cancer; Panel testing.

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Conflict of interest statement

DGE has received travel grants from AstraZeneca. All other authors declare that they have no conflict of interest.

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