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Polygenic scores in Familial breast cancer cases with and without pathogenic variants and the risk of contralateral breast cancer

Kvist, Anders LU orcid ; Kämpe, Anders ; Törngren, Therese LU ; Tesi, Bianca ; Baliakas, Panagiotis ; Borg, Åke LU and Eriksson, Daniel (2025) In Breast Cancer Research 27(1).
Abstract

Background: Polygenic risk scores (PRS) are not yet standard in clinical risk assessments for familial breast cancer in Sweden. This study evaluated the distribution and impact of an established PRS (PRS313) in women undergoing clinical sequencing for hereditary breast cancer. Findings: We integrated PRS313 into a hereditary breast cancer gene panel used in clinical practice and calculated scores for 262 women. Comparisons were made between women with unilateral and contralateral breast cancer, as well as those with and without pathogenic variants in breast cancer susceptibility genes. PRS313 was significantly higher in women with contralateral breast cancer (median + 1.3 SD, n = 33, P = 8e-9) compared... (More)

Background: Polygenic risk scores (PRS) are not yet standard in clinical risk assessments for familial breast cancer in Sweden. This study evaluated the distribution and impact of an established PRS (PRS313) in women undergoing clinical sequencing for hereditary breast cancer. Findings: We integrated PRS313 into a hereditary breast cancer gene panel used in clinical practice and calculated scores for 262 women. Comparisons were made between women with unilateral and contralateral breast cancer, as well as those with and without pathogenic variants in breast cancer susceptibility genes. PRS313 was significantly higher in women with contralateral breast cancer (median + 1.3 SD, n = 33, P = 8e-9) compared to those with unilateral disease (median + 0.66 SD, n = 197, P = 5e-10). Elevated PRS313 was also observed in women with pathogenic variants, including those in high-penetrance genes (+ 0.65 SD) and moderate-penetrance genes (+ 0.93 SD), compared to population controls. Incorporating PRS313 into a clinical risk model (BOADICEA), shifted 20%-27% of women with moderate-penetrance variants and 23%-32% of women without pathogenic variants into different risk categories according to NCCN and NICE guidelines. Conclusions: Women with familial breast cancer showed elevated PRS313, including those with pathogenic variants, contributing to the observed high risk in these families. Integrating PRS into risk assessment and genetic counselling has the potential to refine risk predictions, even among women with breast cancer attributed to monogenic variants.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research
volume
27
issue
1
article number
160
publisher
BioMed Central (BMC)
external identifiers
  • scopus:105015153739
  • pmid:40922009
ISSN
1465-5411
DOI
10.1186/s13058-025-02107-5
language
English
LU publication?
yes
id
514981dc-0c04-4ab8-850c-5572edf93361
date added to LUP
2025-10-02 14:09:16
date last changed
2025-10-16 16:03:57
@article{514981dc-0c04-4ab8-850c-5572edf93361,
  abstract     = {{<p>Background: Polygenic risk scores (PRS) are not yet standard in clinical risk assessments for familial breast cancer in Sweden. This study evaluated the distribution and impact of an established PRS (PRS<sub>313</sub>) in women undergoing clinical sequencing for hereditary breast cancer. Findings: We integrated PRS<sub>313</sub> into a hereditary breast cancer gene panel used in clinical practice and calculated scores for 262 women. Comparisons were made between women with unilateral and contralateral breast cancer, as well as those with and without pathogenic variants in breast cancer susceptibility genes. PRS<sub>313</sub> was significantly higher in women with contralateral breast cancer (median + 1.3 SD, n = 33, P = 8e-9) compared to those with unilateral disease (median + 0.66 SD, n = 197, P = 5e-10). Elevated PRS<sub>313</sub> was also observed in women with pathogenic variants, including those in high-penetrance genes (+ 0.65 SD) and moderate-penetrance genes (+ 0.93 SD), compared to population controls. Incorporating PRS<sub>313</sub> into a clinical risk model (BOADICEA), shifted 20%-27% of women with moderate-penetrance variants and 23%-32% of women without pathogenic variants into different risk categories according to NCCN and NICE guidelines. Conclusions: Women with familial breast cancer showed elevated PRS<sub>313</sub>, including those with pathogenic variants, contributing to the observed high risk in these families. Integrating PRS into risk assessment and genetic counselling has the potential to refine risk predictions, even among women with breast cancer attributed to monogenic variants.</p>}},
  author       = {{Kvist, Anders and Kämpe, Anders and Törngren, Therese and Tesi, Bianca and Baliakas, Panagiotis and Borg, Åke and Eriksson, Daniel}},
  issn         = {{1465-5411}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Breast Cancer Research}},
  title        = {{Polygenic scores in Familial breast cancer cases with and without pathogenic variants and the risk of contralateral breast cancer}},
  url          = {{http://dx.doi.org/10.1186/s13058-025-02107-5}},
  doi          = {{10.1186/s13058-025-02107-5}},
  volume       = {{27}},
  year         = {{2025}},
}