TY - JOUR
T1 - Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - NBCS Collaborators
AU - ABCTB Investigators
AU - KConFab Investigators
AU - KConFab Investigators
AU - NBCS Collaborators
AU - ABCTB Investigators
AU - Kramer, Iris
AU - Hooning, Maartje J.
AU - Mavaddat, Nasim
AU - Hauptmann, Michael
AU - Keeman, Renske
AU - Steyerberg, Ewout W.
AU - Giardiello, Daniele
AU - Antoniou, Antonis C.
AU - Pharoah, Paul D.P.
AU - Canisius, Sander
AU - Abu-Ful, Zumuruda
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Aronson, Kristan J.
AU - Augustinsson, Annelie
AU - Becher, Heiko
AU - Beckmann, Matthias W.
AU - Behrens, Sabine
AU - Benitez, Javier
AU - Bermisheva, Marina
AU - Bogdanova, Natalia V.
AU - Bojesen, Stig E.
AU - Bolla, Manjeet K.
AU - Bonanni, Bernardo
AU - Brauch, Hiltrud
AU - Bremer, Michael
AU - Brucker, Sara Y.
AU - Burwinkel, Barbara
AU - Castelao, Jose E.
AU - Chan, Tsun L.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Chenevix-Trench, Georgia
AU - Choi, Ji Yeob
AU - Clarke, Christine L.
AU - Børresen-Dale, Anne Lise
AU - Sahlberg, Kristine
AU - Ottestad, Lars
AU - Kåresen, Rolf
AU - Schlichting, Ellen
AU - Holmen, Marit Muri
AU - Sauer, Toril
AU - Haakensen, Vilde
AU - Engebråten, Olav
AU - Naume, Bjørn
AU - Fosså, Alexander
AU - Kiserud, Cecile
AU - Reinertsen, Kristin
AU - Helland, Åslaug
AU - Riis, Margit
AU - Daly, Mary
N1 - Publisher Copyright:
© 2020 American Society of Human Genetics
PY - 2020/11/5
Y1 - 2020/11/5
N2 - Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18–1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02–1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547–0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
AB - Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18–1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02–1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547–0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
KW - Adult
KW - Aged
KW - Asian People
KW - Breast Neoplasms/diagnosis
KW - Cohort Studies
KW - Estrogen Receptor alpha/genetics
KW - Female
KW - Gene Expression
KW - Genetic Predisposition to Disease
KW - Genome, Human
KW - Genome-Wide Association Study
KW - Humans
KW - Middle Aged
KW - Multifactorial Inheritance
KW - Neoadjuvant Therapy/methods
KW - Neoplasms, Second Primary/diagnosis
KW - Prognosis
KW - Proportional Hazards Models
KW - Receptor, ErbB-2/genetics
KW - Receptors, Progesterone/genetics
KW - Risk Assessment
KW - White People
UR - http://www.scopus.com/inward/record.url?scp=85094963024&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000587855200005&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.ajhg.2020.09.001
DO - 10.1016/j.ajhg.2020.09.001
M3 - Article
C2 - 33022221
SN - 0002-9297
VL - 107
SP - 837
EP - 848
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -