Prognostic and predictive impact of stroma cells defined by PDGFRb expression in early breast cancer: results from the randomized SweBCG91RT trial.
Early breast cancer
Fibroblasts
PDGFR
Radiotherapy
Tumor microenvironment
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
06
11
2020
accepted:
05
02
2021
pubmed:
5
3
2021
medline:
24
6
2021
entrez:
4
3
2021
Statut:
ppublish
Résumé
Predictive biomarkers are needed to aid the individualization of radiotherapy (RT) in breast cancer. Cancer-associated fibroblasts have been implicated in tumor radioresistance and can be identified by platelet-derived growth factor receptor-beta (PDGFRb). This study aims to analyze how PDGFRb expression affects RT benefit in a large randomized RT trial. PDGFRb was assessed by immunohistochemistry on tissue microarrays from 989 tumors of the SweBCG91RT trial, which enrolled lymph node-negative, stage I/IIA breast cancer patients randomized to RT after breast-conserving surgery. Outcomes were analyzed at 10 years for ipsilateral breast tumor recurrence (IBTR) and any recurrence and 15 years for breast cancer specific death (BCSD). PDGFRb expression correlated with estrogen receptor negativity and younger age. An increased risk for any recurrence was noted in univariable analysis for the medium (HR 1.58, CI 95% 1.11-2.23, p = 0.011) or PDGFRb high group (1.49, 1.06-2.10, p = 0.021) compared to the low group. No differences in IBTR or BCSD risk were detected. RT benefit regarding IBTR risk was significant in the PDGFRb low (0.29, 0.12-0.67, p = 0.004) and medium (0.31, 0.16-0.59, p < 0.001) groups but not the PDGFRb high group (0.64, 0.36-1.11, p = 0.110) in multivariable analysis. Likewise, risk reduction for any recurrence was less pronounced in the PDGFRb high group. No significant interaction between RT and PDGFRb-score could be detected. A higher PDGFRb-score conferred an increased risk of any recurrence, which partly can be explained by its association with estrogen receptor negativity and young age. Reduced RT benefit was noted among patients with high PDGFRb, however without significant interaction.
Identifiants
pubmed: 33661437
doi: 10.1007/s10549-021-06136-4
pii: 10.1007/s10549-021-06136-4
pmc: PMC8062362
doi:
Substances chimiques
PDGFRB protein, human
EC 2.7.10.1
Receptor, Platelet-Derived Growth Factor beta
EC 2.7.10.1
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
45-55Subventions
Organisme : Cancerfonden
ID : Can-2019/0081
Organisme : Radiumhemmets Forskningsfonder
ID : 174292
Organisme : Radiumhemmets Forskningsfonder
ID : 2019:248
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