Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis.
Creators: name: Escala-Garcia, Maria
name: Canisius, Sander
name: Keeman, Renske
name: Beesley, Jonathan
name: Anton-Culver, Hoda
name: Arndt, Volker
name: Augustinsson, Annelie
name: Becher, Heiko
name: Beckmann, Matthias W
name: Behrens, Sabine
name: Bermisheva, Marina
name: Bojesen, Stig E
name: Bolla, Manjeet K
name: Brenner, Hermann
name: Canzian, Federico
name: Castelao, Jose E
name: Chang-Claude, Jenny
name: Chanock, Stephen J
name: Couch, Fergus J
name: Czene, Kamila
name: Daly, Mary B
name: Dennis, Joe
name: Devilee, Peter
name: Dörk, Thilo
name: Dunning, Alison M
name: Easton, Douglas F
name: Ekici, Arif B
name: Eliassen, A Heather
name: Fasching, Peter A
name: Flyger, Henrik
name: Gago-Dominguez, Manuela
name: García-Closas, Montserrat
name: García-Sáenz, José A
name: Geisler, Jürgen
name: Giles, Graham G
name: Grip, Mervi
name: Gündert, Melanie
name: Hahnen, Eric
name: Haiman, Christopher A
name: Håkansson, Niclas
name: Hall, Per
name: Hamann, Ute
name: Hartikainen, Jaana M
name: Heemskerk-Gerritsen, Bernadette A M
name: Hollestelle, Antoinette
name: Hoppe, Reiner
name: Hopper, John L
name: Hunter, David J
name: Jacot, William
name: Jakubowska, Anna
name: John, Esther M
name: Jung, Audrey Y
name: Kaaks, Rudolf
name: Khusnutdinova, Elza
name: Koppert, Linetta B
name: Kraft, Peter
name: Kristensen, Vessela N
name: Kurian, Allison W
name: Lambrechts, Diether
name: Le Marchand, Loic
name: Lindblom, Annika
name: Luben, Robert N
name: Lubiński, Jan
name: Mannermaa, Arto
name: Manoochehri, Mehdi
name: Margolin, Sara
name: Mavroudis, Dimitrios
name: Muranen, Taru A
name: Nevanlinna, Heli
name: Olshan, Andrew F
name: Olsson, Håkan
name: Park-Simon, Tjoung-Won
name: Patel, Alpa V
name: Peterlongo, Paolo
name: Pharoah, Paul D P
name: Punie, Kevin
name: Radice, Paolo
name: Rennert, Gad
name: Rennert, Hedy S
name: Romero, Atocha
name: Roylance, Rebecca
name: Rüdiger, Thomas
name: Ruebner, Matthias
name: Saloustros, Emmanouil
name: Sawyer, Elinor J
name: Schmutzler, Rita K
name: Schoemaker, Minouk J
name: Scott, Christopher
name: Southey, Melissa C
name: Surowy, Harald
name: Swerdlow, Anthony J
name: Tamimi, Rulla M
name: Teras, Lauren R
name: Thomas, Emilie
name: Tomlinson, Ian
name: Troester, Melissa A
name: Vachon, Celine M
name: Wang, Qin
name: Winqvist, Robert
name: Wolk, Alicja
name: Ziogas, Argyrios
name: Michailidou, Kyriaki
name: Chenevix-Trench, Georgia
name: Bachelot, Thomas
name: Schmidt, Marjanka K
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021

description: Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis. We used data from the Breast Cancer Association Consortium (BCAC) including 1062 women of European ancestry with metastatic breast cancer, 606 of whom died of breast cancer. We identified two germline variants on chromosome 1, rs138569520 and rs146023652, significantly associated with breast cancer-specific survival (P = 3.19 × 10<sup>-8</sup> and 4.42 × 10<sup>-8</sup>). In silico analysis suggested a potential regulatory effect of the variants on the nearby target genes SDE2 and H3F3A. However, the variants showed no evidence of association in a smaller replication dataset. The validation dataset was obtained from the SNPs to Risk of Metastasis (StoRM) study and included 293 patients with metastatic primary breast cancer at diagnosis. Ultimately, larger replication studies are needed to confirm the identified associations.