TY - JOUR
T1 - 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
AU - Morra, Anna
AU - Escala-Garcia, Maria
AU - NBCS Collaborators
AU - ABCTB Investigators
AU - kConFab Investigators
AU - kConFab Investigators
AU - Beesley, Jonathan
AU - Keeman, Renske
AU - Canisius, Sander
AU - Ahearn, Thomas U.
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Auer, Paul L.
AU - Augustinsson, Annelie
AU - Beane Freeman, Laura E.
AU - Becher, Heiko
AU - Beckmann, Matthias W.
AU - Behrens, Sabine
AU - Bojesen, Stig E.
AU - Bolla, Manjeet K.
AU - Brenner, Hermann
AU - Brüning, Thomas
AU - Buys, Saundra S.
AU - Caan, Bette
AU - Campa, Daniele
AU - Canzian, Federico
AU - Castelao, Jose E.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Cheng, Ting Yuan David
AU - Clarke, Christine L.
AU - Børresen-Dale, Anne Lise
AU - Sahlberg, Kristine K.
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 E.
AU - Reinertsen, Kristin V.
AU - Helland, Åslaug
AU - Riis, Margit
AU - Geisler, Jürgen
AU - Grenaker Alnæs, Grethe I.
AU - Colonna, Sarah V.
AU - Hooning, Maartje J.
AU - Jager, Agnes
AU - Kraft, Peter
AU - Martens, John W.M.
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021/8/18
Y1 - 2021/8/18
N2 - Background: Given 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. Methods: We 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 < 0.15). Results: Evidence 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. Conclusions: We 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.
AB - Background: Given 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. Methods: We 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 < 0.15). Results: Evidence 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. Conclusions: We 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.
UR - http://www.scopus.com/inward/record.url?scp=85114653695&partnerID=8YFLogxK
U2 - 10.1186/s13058-021-01450-7
DO - 10.1186/s13058-021-01450-7
M3 - Article
C2 - 34407845
AN - SCOPUS:85114653695
SN - 1465-5411
VL - 23
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 86
ER -
