TY - JOUR
T1 - Multigene assessment of genetic risk for women for two or more breast cancers
AU - Weitzel, Jeffrey N.
AU - Kidd, John
AU - Bernhisel, Ryan
AU - Shehayeb, Susan
AU - Frankel, Paul
AU - Blazer, Kathleen R.
AU - Turco, Diana
AU - Nehoray, Bita
AU - McGreevy, Kim
AU - Svirsky, Kira
AU - Brown, Krystal
AU - Gardiner, Anna
AU - Daly, Mary
AU - Hughes, Elisha
AU - Cummings, Shelly
AU - Saam, Jennifer
AU - Slavin, Thomas P.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: The prevalence, penetrance, and spectrum of pathogenic variants that predispose women to two or more breast cancers is largely unknown. Methods: We queried clinical and genetic data from women with one or more breast cancer diagnosis who received multigene panel testing between 2013 and 2018. Clinical data were obtained from provider-completed test request forms. For each gene on the panel, a multivariable logistic regression model was constructed to test for association with risk of multiple breast cancer diagnoses. Models accounted for age of diagnosis, personal and family cancer history, and ancestry. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results: This study included 98,979 patients: 88,759 (89.7%) with a single breast cancer and 10,220 (10.3%) with ≥ 2 breast cancers. Of women with two or more breast cancers, 13.2% had a pathogenic variant in a cancer predisposition gene compared to 9.4% with a single breast cancer. BRCA1, BRCA2, CDH1, CHEK2, MSH6, PALB2, PTEN, and TP53 were significantly associated with two or more breast cancers, with ORs ranging from 1.35 for CHEK2 to 3.80 for PTEN. Overall, pathogenic variants in all breast cancer risk genes combined were associated with both metachronous (OR 1.65, 95% CI 1.53–1.79, p = 7.2 × 10–33) and synchronous (OR 1.33, 95% CI 1.19–1.50, p = 2.4 × 10–6) breast cancers. Conclusions: This study demonstrated that several high and moderate penetrance breast cancer susceptibility genes are associated with ≥ 2 breast cancers, affirming the association of two or more breast cancers with diverse genetic etiologies.
AB - Purpose: The prevalence, penetrance, and spectrum of pathogenic variants that predispose women to two or more breast cancers is largely unknown. Methods: We queried clinical and genetic data from women with one or more breast cancer diagnosis who received multigene panel testing between 2013 and 2018. Clinical data were obtained from provider-completed test request forms. For each gene on the panel, a multivariable logistic regression model was constructed to test for association with risk of multiple breast cancer diagnoses. Models accounted for age of diagnosis, personal and family cancer history, and ancestry. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results: This study included 98,979 patients: 88,759 (89.7%) with a single breast cancer and 10,220 (10.3%) with ≥ 2 breast cancers. Of women with two or more breast cancers, 13.2% had a pathogenic variant in a cancer predisposition gene compared to 9.4% with a single breast cancer. BRCA1, BRCA2, CDH1, CHEK2, MSH6, PALB2, PTEN, and TP53 were significantly associated with two or more breast cancers, with ORs ranging from 1.35 for CHEK2 to 3.80 for PTEN. Overall, pathogenic variants in all breast cancer risk genes combined were associated with both metachronous (OR 1.65, 95% CI 1.53–1.79, p = 7.2 × 10–33) and synchronous (OR 1.33, 95% CI 1.19–1.50, p = 2.4 × 10–6) breast cancers. Conclusions: This study demonstrated that several high and moderate penetrance breast cancer susceptibility genes are associated with ≥ 2 breast cancers, affirming the association of two or more breast cancers with diverse genetic etiologies.
KW - BRCA1
KW - BRCA2
KW - Breast cancer
KW - Hereditary breast cancer
KW - Multiple breast cancers
KW - Second breast cancer
UR - http://www.scopus.com/inward/record.url?scp=85103990713&partnerID=8YFLogxK
U2 - 10.1007/s10549-021-06201-y
DO - 10.1007/s10549-021-06201-y
M3 - Article
C2 - 33826040
AN - SCOPUS:85103990713
SN - 0167-6806
VL - 188
SP - 759
EP - 768
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 3
ER -