In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 10 ( 2023-04-01), p. 1849-1863
Kurzfassung:
A polygenic risk score (PRS) consisting of 313 common genetic variants (PRS 313 ) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS 313 with clinicopathologic characteristics of, and survival following, breast cancer. METHODS Women 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 PRS 313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS 313 (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. RESULTS The PRS 313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS 313 was associated with lower grade, hormone receptor–positive status, and smaller tumor size. In MINDACT, PRS 313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS 313 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. CONCLUSION An increased PRS 313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS 313 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 PRS 313 as increasing PRS 313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.22.01978
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2023
ZDB Id:
2005181-5
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