TY - JOUR

T1 - Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival

AU - Lopes Cardozo, Josephine M.N.

AU - Andrulis, Irene L.

AU - Bojesen, Stig E.

AU - Dörk, Thilo

AU - Eccles, Diana M.

AU - Fasching, Peter A.

AU - Hooning, Maartje J.

AU - Keeman, Renske

AU - Nevanlinna, Heli

AU - Rutgers, Emiel J.T.

AU - Easton, Douglas F.

AU - Hall, Per

AU - Pharoah, Paul D.P.

AU - Van 't Veer, Laura J.

AU - Schmidt, Marjanka K.

AU - On Behalf Of The Breast Cancer Association Consortium And MINDACT Collaborators

N1 - Publisher Copyright: © 2023 American Society of Clinical Oncology.

PY - 2023

Y1 - 2023

N2 - PURPOSEA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.METHODSWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.RESULTSThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.CONCLUSIONAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

AB - PURPOSEA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.METHODSWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.RESULTSThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.CONCLUSIONAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.

U2 - 10.1200/JCO.22.01978

DO - 10.1200/JCO.22.01978

M3 - Journal article

C2 - 36689693

AN - SCOPUS:85151313050

VL - 41

SP - 1849

EP - 1863

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 10

ER -