Associations of a Breast Cancer Polygenic Risk Score With Tumor Characteristics and Survival. Issue 10 (1st April 2023)

• Record Type: Journal Article
• Authors: Lopes Cardozo, Josephine M.N.; Andrulis, Irene L.; Bojesen, Stig E.; Dörk, Thilo; Eccles, Diana M.; Fasching, Peter A.; Hooning, Maartje J.; Keeman, Renske; Nevanlinna, Heli; Rutgers, Emiel J.T.; Easton, Douglas F.; Hall, Per; Pharoah, Paul D.P.; van 't Veer, Laura J.; Schmidt, Marjanka K.
• Other Names: Ahearn Thomas U. collaborator.; Anton-Culver Hoda collaborator.; Arndt Volker collaborator.; Auer Paul L. collaborator.; Augustinsson Annelie collaborator.; Beane Freeman Laura E. collaborator.; Becher Heiko collaborator.; Beckmann Matthias W. collaborator.; Behrens Sabine collaborator.; Benitez Javier collaborator.; Bermisheva Marina collaborator.; Blomqvist Carl collaborator.; Bolla Manjeet K. collaborator.; Bonanni Bernardo collaborator.; Boyle Terry collaborator.; Brenner Hermann collaborator.; Brucker Sara Y. collaborator.; Brüning Thomas collaborator.; Burwinkel Barbara collaborator.; Buys Saundra S. collaborator.; Camp Nicola J. collaborator.; Canzian Federico collaborator.; Cardoso Fatima collaborator.; Castelao Jose E. collaborator.; Cessna Melissa H. collaborator.; Chan Tsun L. collaborator.; Chang-Claude Jenny collaborator.; Chenevix-Trench Georgia collaborator.; Choi Ji-Yeob collaborator.; Colonna Sarah V. collaborator.; Copson Ellen collaborator.; Couch Fergus J. collaborator.; Cox Angela collaborator.; Cross Simon S. collaborator.; Czene Kamila collaborator.; Daly Mary B. collaborator.; Dennis Joe collaborator.; Devilee Peter collaborator.; Drukker Caroline A. collaborator.; Dunning Alison M. collaborator.; Dwek Miriam collaborator.; Eliassen A. Heather collaborator.; Engel Christoph collaborator.; Evans D. Gareth collaborator.; Figueroa Jonine D. collaborator.; Fletcher Olivia collaborator.; Flyger Henrik collaborator.; Gago-Dominguez Manuela collaborator.; García-Closas Montserrat collaborator.; García-Sáenz José A. collaborator.; Genkinger Jeanine collaborator.; Giles Graham G. collaborator.; González-Neira Anna collaborator.; Guénel Pascal collaborator.; Gündert Melanie collaborator.; Hahnen Eric collaborator.; Haiman Christopher A. collaborator.; Håkansson Niclas collaborator.; Hamann Ute collaborator.; Hartman Mikael collaborator.; Heemskerk-Gerritsen Bernadette A.M. collaborator.; Hein Alexander collaborator.; Ho Weang-Kee collaborator.; Hoppe Reiner collaborator.; Hopper John L. collaborator.; Houlston Richard S. collaborator.; Howell Anthony collaborator.; Hunter David J. collaborator.; Ito Hidemi collaborator.; Jakubowska Anna collaborator.; Jernström Helena collaborator.; John Esther M. collaborator.; Johnson Nichola collaborator.; Jones Michael E. collaborator.; Joseph Vijai collaborator.; Kaaks Rudolf collaborator.; Kang Daehee collaborator.; Kim Sung-Won collaborator.; Kitahara Cari M. collaborator.; Koppert Linetta B. collaborator.; Kosma Veli-Matti collaborator.; Kraft Peter collaborator.; Kristensen Vessela N. collaborator.; Kubelka-Sabit Katerina collaborator.; Koutros Stella collaborator.; Kurian Allison W. collaborator.; Kwong Ava collaborator.; Lacey James V. collaborator.; Lambrechts Diether collaborator.; Le Marchand Loic collaborator.; Li Jingmei collaborator.; Lubiński Jan collaborator.; Lush Michael collaborator.; Mannermaa Arto collaborator.; Manoochehri Mehdi collaborator.; Margolin Sara collaborator.; Matsuo Keitaro collaborator.; Mavroudis Dimitrios collaborator.; Michailidou Kyriaki collaborator.; Milne Roger L. collaborator.; Mohd Taib Nur Aishah collaborator.; Mulligan Anna Marie collaborator.; Neven Patrick collaborator.; Newman William G. collaborator.; Obi Nadia collaborator.; Offit Kenneth collaborator.; Olshan Andrew F. collaborator.; Park Sue K. collaborator.; Park-Simon Tjoung-Won collaborator.; Patel Alpa V. collaborator.; Plaseska-Karanfilska Dijana collaborator.; Poncet Coralie collaborator.; Prentice Ross L. collaborator.; Presneau Nadege collaborator.; Prevos Renate collaborator.; Pylkäs Katri collaborator.; Radice Paolo collaborator.; Rennert Gad collaborator.; Rennert Hedy S. collaborator.; Romero Atocha collaborator.; Saloustros Emmanouil collaborator.; Sawyer Elinor J. collaborator.; Schmutzler Rita K. collaborator.; Schwentner Lukas collaborator.; Scott Christopher collaborator.; Shah Mitul collaborator.; Shen Chen-Yang collaborator.; Shu Xiao-Ou collaborator.; Sim Xueling collaborator.; Southey Melissa C. collaborator.; Stone Jennifer collaborator.; Stram Daniel O. collaborator.; Tamimi Rulla M. collaborator.; Teo Soo Hwang collaborator.; Teras Lauren R. collaborator.; Terry Mary Beth collaborator.; Tomczyk Katarzyna collaborator.; Tomlinson Ian collaborator.; Troester Melissa A. collaborator.; Truong Thérèse collaborator.; Vachon Celine M. collaborator.; van Ongeval Chantal collaborator.; Wang Qin collaborator.; Wappenschmidt Barbara collaborator.; Wendt Camilla collaborator.; Winqvist Robert collaborator.; Wolk Alicja collaborator.; Wu Anna H. collaborator.; Yadav Siddhartha collaborator.; Yip Cheng Har collaborator.; Zheng Wei collaborator.; Ziogas Argyrios collaborator.;
• Is Part Of: Journal of clinical oncology. Volume 41:Issue 10(2023)
• Page Start: 1849
• Page End: 1863
• Publication Date: 2023-04-01
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.22.01978
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : 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.