TY - JOUR
T1 - Extended gene panel testing in lobular breast cancer
AU - Van Veen, Elke
AU - Evans, D Gareth
AU - Harkness, Elaine
AU - Byers, Helen
AU - Ellingford, Jamie
AU - Woodward, Emma
AU - Bowers, Naomi
AU - Wallace, Andrew J
AU - Howell, Sacha
AU - Howell, Tony
AU - Lalloo, Fiona
AU - Newman, William
AU - Smith, Miriam J
PY - 2021/3/3
Y1 - 2021/3/3
N2 - 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.
AB - 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.
M3 - Article
SN - 1389-9600
JO - Familial Cancer
JF - Familial Cancer
ER -
