Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.
Creators: name: Morra, Anna
name: Escala-Garcia, Maria
name: Beesley, Jonathan
name: Keeman, Renske
name: Canisius, Sander
name: Ahearn, Thomas U
name: Andrulis, Irene L
name: Anton-Culver, Hoda
name: Arndt, Volker
name: Auer, Paul L
name: Augustinsson, Annelie
name: Beane Freeman, Laura E
name: Becher, Heiko
name: Beckmann, Matthias W
name: Behrens, Sabine
name: Bojesen, Stig E
name: Bolla, Manjeet K
name: Brenner, Hermann
name: Brüning, Thomas
name: Buys, Saundra S
name: Caan, Bette
name: Campa, Daniele
name: Canzian, Federico
name: Castelao, Jose E
name: Chang-Claude, Jenny
name: Chanock, Stephen J
name: Cheng, Ting-Yuan David
name: Clarke, Christine L
name: Colonna, Sarah V
name: Couch, Fergus J
name: Cox, Angela
name: Cross, Simon S
name: Czene, Kamila
name: Daly, Mary B
name: Dennis, Joe
name: Dörk, Thilo
name: Dossus, Laure
name: Dunning, Alison M
name: Dwek, Miriam
name: Eccles, Diana M
name: Ekici, Arif B
name: Eliassen, A Heather
name: Eriksson, Mikael
name: Evans, D Gareth
name: Fasching, Peter A
name: Flyger, Henrik
name: Fritschi, Lin
name: Gago-Dominguez, Manuela
name: García-Sáenz, José A
name: Giles, Graham G
name: Grip, Mervi
name: Guénel, Pascal
name: Gündert, Melanie
name: Hahnen, Eric
name: Haiman, Christopher A
name: Håkansson, Niclas
name: Hall, Per
name: Hamann, Ute
name: Hart, Steven N
name: Hartikainen, Jaana M
name: Hartmann, Arndt
name: He, Wei
name: Hooning, Maartje J
name: Hoppe, Reiner
name: Hopper, John L
name: Howell, Anthony
name: Hunter, David J
name: Jager, Agnes
name: Jakubowska, Anna
name: Janni, Wolfgang
name: John, Esther M
name: Jung, Audrey Y
name: Kaaks, Rudolf
name: Keupers, Machteld
name: Kitahara, Cari M
name: Koutros, Stella
name: Kraft, Peter
name: Kristensen, Vessela N
name: Kurian, Allison W
name: Lacey, James V
name: Lambrechts, Diether
name: Le Marchand, Loic
name: Lindblom, Annika
name: Linet, Martha
name: Luben, Robert N
name: Lubiński, Jan
name: Lush, Michael
name: Mannermaa, Arto
name: Manoochehri, Mehdi
name: Margolin, Sara
name: Martens, John W M
name: Martinez, Maria Elena
name: Mavroudis, Dimitrios
name: Michailidou, Kyriaki
name: Milne, Roger L
name: Mulligan, Anna Marie
name: Muranen, Taru A
name: Nevanlinna, Heli
name: Newman, William G
name: Nielsen, Sune F
name: Nordestgaard, Børge G
name: Olshan, Andrew F
name: Olsson, Håkan
name: Orr, Nick
name: Park-Simon, Tjoung-Won
name: Patel, Alpa V
name: Peissel, Bernard
name: Peterlongo, Paolo
name: Plaseska-Karanfilska, Dijana
name: Prajzendanc, Karolina
name: Prentice, Ross
name: Presneau, Nadege
name: Rack, Brigitte
name: Rennert, Gad
name: Rennert, Hedy S
name: Rhenius, Valerie
name: Romero, Atocha
name: Roylance, Rebecca
name: Ruebner, Matthias
name: Saloustros, Emmanouil
name: Sawyer, Elinor J
name: Schmutzler, Rita K
name: Schneeweiss, Andreas
name: Scott, Christopher
name: Shah, Mitul
name: Smichkoska, Snezhana
name: Southey, Melissa C
name: Stone, Jennifer
name: Surowy, Harald
name: Swerdlow, Anthony J
name: Tamimi, Rulla M
name: Tapper, William J
name: Teras, Lauren R
name: Terry, Mary Beth
name: Tollenaar, Rob A E M
name: Tomlinson, Ian
name: Troester, Melissa A
name: Truong, Thérèse
name: Vachon, Celine M
name: Wang, Qin
name: Hurson, Amber N
name: Winqvist, Robert
name: Wolk, Alicja
name: Ziogas, Argyrios
name: Brauch, Hiltrud
name: García-Closas, Montserrat
name: Pharoah, Paul D P
name: Easton, Douglas F
name: Chenevix-Trench, Georgia
name: Schmidt, Marjanka K
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Systemic Treatment
Tumor Biology
Breast Cancer-specific Survival
Patient Subgroups
Common Germline Genetic Variants

description: BackgroundGiven the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients.MethodsWe performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP ResultsEvidence of associations with breast cancer-specific survival was observed in three patient subgroups, with variant rs5934618 in patients with grade 3 tumors (15-year-hazard ratio (HR) [95% confidence interval (CI)] 1.32 [1.20, 1.45], P = 1.4E-08, BFDP = 0.01, per G allele); variant rs4679741 in patients with ER-positive tumors treated with endocrine therapy (15-year-HR [95% CI] 1.18 [1.11, 1.26], P = 1.6E-07, BFDP = 0.09, per G allele); variants rs1106333 (15-year-HR [95% CI] 1.68 [1.39,2.03], P = 5.6E-08, BFDP = 0.12, per A allele) and rs78754389 (5-year-HR [95% CI] 1.79 [1.46,2.20], P = 1.7E-08, BFDP = 0.07, per A allele), in patients with ER-negative tumors treated with chemotherapy.ConclusionsWe found evidence of four loci associated with breast cancer-specific survival within three patient subgroups. There was limited evidence for the existence of associations in other patient subgroups. However, the power for many subgroups is limited due to the low number of events. Even so, our results suggest that the impact of common germline genetic variants on breast cancer-specific survival might be limited.