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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

Morra, Anna ; Escala-Garcia, Maria ; Beesley, Jonathan ; Keeman, Renske ; Canisius, Sander ; Ahearn, Thomas U. ; Andrulis, Irene L. ; Anton-Culver, Hoda ; Arndt, Volker and Auer, Paul L. , et al. (2021) In Breast cancer research : BCR 23(1). p.86-86
Abstract

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... (More)

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.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Breast cancer-specific survival, Common germline genetic variants, Patient subgroups, Systemic treatment, Tumor biology
in
Breast cancer research : BCR
volume
23
issue
1
pages
1 pages
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85114653695
  • pmid:34407845
ISSN
1465-5411
DOI
10.1186/s13058-021-01450-7
language
English
LU publication?
yes
id
e9a6de01-9f66-4acb-b5e7-9687cfe324c5
date added to LUP
2021-10-11 11:33:48
date last changed
2024-08-25 00:39:31
@article{e9a6de01-9f66-4acb-b5e7-9687cfe324c5,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Morra, Anna and Escala-Garcia, Maria and Beesley, Jonathan and Keeman, Renske and Canisius, Sander and Ahearn, Thomas U. and Andrulis, Irene L. and Anton-Culver, Hoda and Arndt, Volker and Auer, Paul L. and Augustinsson, Annelie and Beane Freeman, Laura E. and Becher, Heiko and Beckmann, Matthias W. and Behrens, Sabine and Bojesen, Stig E. and Bolla, Manjeet K. and Brenner, Hermann and Brüning, Thomas and Buys, Saundra S. and Caan, Bette and Campa, Daniele and Canzian, Federico and Castelao, Jose E. and Chang-Claude, Jenny and Chanock, Stephen J. and Cheng, Ting Yuan David and Clarke, Christine L. and Colonna, Sarah V. and Couch, Fergus J. and Cox, Angela and Cross, Simon S. and Czene, Kamila and Daly, Mary B. and Dennis, Joe and Dörk, Thilo and Dossus, Laure and Dunning, Alison M. and Dwek, Miriam and Eccles, Diana M. and Ekici, Arif B. and Eliassen, A. Heather and Eriksson, Mikael and Evans, D. Gareth and Fasching, Peter A. and Flyger, Henrik and Fritschi, Lin and Gago-Dominguez, Manuela and Hall, Per and Olsson, Håkan}},
  issn         = {{1465-5411}},
  keywords     = {{Breast cancer-specific survival; Common germline genetic variants; Patient subgroups; Systemic treatment; Tumor biology}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{1}},
  pages        = {{86--86}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Breast cancer research : BCR}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1186/s13058-021-01450-7}},
  doi          = {{10.1186/s13058-021-01450-7}},
  volume       = {{23}},
  year         = {{2021}},
}