{Reference Type}: Journal Article
{Title}: Extended gene panel testing in lobular breast cancer.
{Author}: van Veen EM;Evans DG;Harkness EF;Byers HJ;Ellingford JM;Woodward ER;Bowers NL;Wallace AJ;Howell SJ;Howell A;Lalloo F;Newman WG;Smith MJ;
{Journal}: Fam Cancer
{Volume}: 0
{Issue}: 0
{Year}: Mar 2021 25
{Factor}: 2.446
{DOI}: 10.1007/s10689-021-00241-5
{Abstract}: <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.