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Prognostic Differences of Adjuvant Radiotherapy in Breast Cancer Cohorts Based on PRLR Genotypes, Expression, and Transcriptional Network Regulation

Munnik, Floor LU ; Gonçalves de Oliveira, Kelin LU ; Godina, Christopher LU orcid ; Isaksson, Karolin LU and Jernström, Helena LU (2025) In Cancers 17(14).
Abstract
Background: Prolactin receptor (PRLR) signaling affects breastfeeding and potentially breast cancer treatment response. Methods: The prognostic impact of 20 PRLR single nucleotide polymorphisms (SNPs) in relation to adjuvant treatment groups in patients with primary breast cancer (n = 1701, 2002–2016, Sweden) was evaluated. Genomic DNA was genotyped on Illumina OncoArray, and survival analyses with up to 15-year follow-up were performed. Interaction models, adjusted for potential confounders, were created with different adjuvant treatment modalities: chemotherapy, radiotherapy, tamoxifen, and aromatase inhibitors. Results: Five SNPs (rs7734558, rs6860397, rs2962101, rs7732013, and rs4703503) showed interactions with radiotherapy and were... (More)
Background: Prolactin receptor (PRLR) signaling affects breastfeeding and potentially breast cancer treatment response. Methods: The prognostic impact of 20 PRLR single nucleotide polymorphisms (SNPs) in relation to adjuvant treatment groups in patients with primary breast cancer (n = 1701, 2002–2016, Sweden) was evaluated. Genomic DNA was genotyped on Illumina OncoArray, and survival analyses with up to 15-year follow-up were performed. Interaction models, adjusted for potential confounders, were created with different adjuvant treatment modalities: chemotherapy, radiotherapy, tamoxifen, and aromatase inhibitors. Results: Five SNPs (rs7734558, rs6860397, rs2962101, rs7732013, and rs4703503) showed interactions with radiotherapy and were utilized to create seven combined genotypes: six unique and one ‘rare’. Patients carrying combined genotype AG/GG/TT/CC/TC or ‘rare’ combinations derived greater benefits from radiotherapy than other patient groups (both HRadj ≤ 0.29, Bonferroni-adjusted Pint ≤ 0.039). Expression Quantitative Trait Loci (eQTL) analysis revealed that three PRLR SNPs were associated with decreased PRLR expression. To explore potential SNP-associated effects, gene expression and transcriptional networks were analyzed in the METABRIC cohort and indicated that PRLR-low tumors were associated with reduced DNA repair signaling and enhanced anti-tumoral immunity. Conclusions: PRLR merits further evaluation as a putative pharmacogenomic biomarker in relation to radiotherapy for breast cancer patients. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancers
volume
17
issue
14
article number
2378
publisher
MDPI AG
external identifiers
  • pmid:40723262
  • scopus:105011484384
ISSN
2072-6694
DOI
10.3390/cancers17142378
language
English
LU publication?
yes
id
b563aa32-af47-4fb2-9b8a-0084dfac2a07
date added to LUP
2025-09-09 11:01:48
date last changed
2025-10-14 09:08:17
@article{b563aa32-af47-4fb2-9b8a-0084dfac2a07,
  abstract     = {{Background: Prolactin receptor (PRLR) signaling affects breastfeeding and potentially breast cancer treatment response. Methods: The prognostic impact of 20 PRLR single nucleotide polymorphisms (SNPs) in relation to adjuvant treatment groups in patients with primary breast cancer (n = 1701, 2002–2016, Sweden) was evaluated. Genomic DNA was genotyped on Illumina OncoArray, and survival analyses with up to 15-year follow-up were performed. Interaction models, adjusted for potential confounders, were created with different adjuvant treatment modalities: chemotherapy, radiotherapy, tamoxifen, and aromatase inhibitors. Results: Five SNPs (rs7734558, rs6860397, rs2962101, rs7732013, and rs4703503) showed interactions with radiotherapy and were utilized to create seven combined genotypes: six unique and one ‘rare’. Patients carrying combined genotype AG/GG/TT/CC/TC or ‘rare’ combinations derived greater benefits from radiotherapy than other patient groups (both HRadj ≤ 0.29, Bonferroni-adjusted Pint ≤ 0.039). Expression Quantitative Trait Loci (eQTL) analysis revealed that three PRLR SNPs were associated with decreased PRLR expression. To explore potential SNP-associated effects, gene expression and transcriptional networks were analyzed in the METABRIC cohort and indicated that PRLR-low tumors were associated with reduced DNA repair signaling and enhanced anti-tumoral immunity. Conclusions: PRLR merits further evaluation as a putative pharmacogenomic biomarker in relation to radiotherapy for breast cancer patients.}},
  author       = {{Munnik, Floor and Gonçalves de Oliveira, Kelin and Godina, Christopher and Isaksson, Karolin and Jernström, Helena}},
  issn         = {{2072-6694}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{14}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Prognostic Differences of Adjuvant Radiotherapy in Breast Cancer Cohorts Based on PRLR Genotypes, Expression, and Transcriptional Network Regulation}},
  url          = {{http://dx.doi.org/10.3390/cancers17142378}},
  doi          = {{10.3390/cancers17142378}},
  volume       = {{17}},
  year         = {{2025}},
}