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Associations of a B...
Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival
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Lopes Cardozo, Josephine M N (author)
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Andrulis, Irene L (author)
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Bojesen, Stig E (author)
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Dörk, Thilo (author)
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Eccles, Diana M (author)
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- Augustinsson, Annelie (author)
- Lund University,Lunds universitet,Vård i högteknologisk miljö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Care in high technological environments,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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Hooning, Maartje J (author)
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Keeman, Renske (author)
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Nevanlinna, Heli (author)
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Rutgers, Emiel J T (author)
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Easton, Douglas F (author)
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- Hall, Per (author)
- Karolinska Institutet
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Pharoah, Paul D P (author)
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van 't Veer, Laura J (author)
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Schmidt, Marjanka K (author)
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- Augustinsson, Annelie (creator_code:cre_t)
- Lund University,Lunds universitet,Vård i högteknologisk miljö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Care in high technological environments,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
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(creator_code:org_t)
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- 2023
- 2023
- English.
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In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 41:10, s. 1849-1863
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Abstract
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- PURPOSE: A 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.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 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.RESULTS: The 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.CONCLUSION: An 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Female
- Humans
- Breast Neoplasms/pathology
- Risk Factors
- Prognosis
- Proportional Hazards Models
- Breast/pathology
Publication and Content Type
- art (subject category)
- ref (subject category)
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Lopes Cardozo, J ...
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Andrulis, Irene ...
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Bojesen, Stig E
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Dörk, Thilo
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Eccles, Diana M
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Augustinsson, An ...
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show more...
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Hooning, Maartje ...
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Keeman, Renske
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Nevanlinna, Heli
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Rutgers, Emiel J ...
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Easton, Douglas ...
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Hall, Per
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Pharoah, Paul D ...
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van 't Veer, Lau ...
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Schmidt, Marjank ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Journal of clini ...
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Lund University
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Karolinska Institutet