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Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival.
Pubmed ID
36689693 (View this publication on the PubMed website)
Digital Object Identifier
J Clin Oncol. 2023 Jan 23; Pages JCO2201978
Lopes Cardozo JMN , Andrulis IL , Bojesen SE , Dörk T , Eccles DM , Fasching PA , Hooning MJ , Keeman R , Nevanlinna H , Rutgers EJT , Easton DF , Hall P , Pharoah PDP , van 't Veer LJ , Schmidt MK , Breast Cancer Association Consortium and MINDACT Collaborators
  • Department of Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.
  • Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark.
  • Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.
  • Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
  • Department of Gynecology and Obstetricss, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, University Hospital Erlangen, Erlangen, Germany.
  • Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
  • Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
  • Department of Obstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
  • Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom. more
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.

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.

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