In:
Familial Cancer, Springer Science and Business Media LLC, Vol. 21, No. 2 ( 2022-04), p. 129-136
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.
Type of Medium:
Online Resource
ISSN:
1389-9600
,
1573-7292
DOI:
10.1007/s10689-021-00241-5
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2015448-3
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