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Immune infiltrate in the primary tumor predicts effect of adjuvant radiotherapy in breast cancer : Results from the randomized SweBCG91RT trial

Tullberg, Axel Stenmark ; Puttonen, Henri A.J. ; Sjöström, Martin ; Holmberg, Erik ; Laura Chang, S. ; Feng, Felix Y. ; Speers, Corey ; Pierce, Lori J. ; Lundstedt, Dan and Killander, Fredrika LU , et al. (2021) In Clinical Cancer Research 27(3). p.749-758
Abstract

Purpose: Tumor-infiltrating immune cells play a key role in tumor progression. The purpose of this study was to analyze whether the immune infiltrate predicts benefit from postoperative radiotherapy in a large randomized breast cancer radiotherapy trial. Experimental Design: In the SweBCG91RT trial, patients with stage I and II breast cancer were randomized to breast-conserving surgery (BCS) and postoperative radiotherapy or to BCS only and followed for a median time of 15.2 years. The primary tumor immune infiltrate was quantified through two independent methods: IHC and gene expression profiling. For IHC analyses, the absolute stromal area occupied by CD8þ T cells and FOXP3þ T cells, respectively, was used to... (More)

Purpose: Tumor-infiltrating immune cells play a key role in tumor progression. The purpose of this study was to analyze whether the immune infiltrate predicts benefit from postoperative radiotherapy in a large randomized breast cancer radiotherapy trial. Experimental Design: In the SweBCG91RT trial, patients with stage I and II breast cancer were randomized to breast-conserving surgery (BCS) and postoperative radiotherapy or to BCS only and followed for a median time of 15.2 years. The primary tumor immune infiltrate was quantified through two independent methods: IHC and gene expression profiling. For IHC analyses, the absolute stromal area occupied by CD8þ T cells and FOXP3þ T cells, respectively, was used to define the immune infiltrate. For gene expression analyses, immune cells found to be prognostic in independent datasets were pooled into two groups consisting of antitumoral and protumoral immune cells, respectively. Results: An antitumoral immune response in the primary tumor was associated with a reduced risk of breast cancer recurrence and predicted less benefit from adjuvant radiotherapy. The interaction between radiotherapy and immune phenotype was significant for any recurrence in both the IHC and gene expression analyses (P ¼ 0.039 and P ¼ 0.035) and was also significant for ipsilateral breast tumor recurrence in the gene expression analyses (P ¼ 0.025). Conclusions: Patients with an antitumoral immune infiltrate in the primary tumor have a reduced risk of any recurrence and may derive less benefit from adjuvant radiotherapy. These results may impact decisions regarding postoperative radiotherapy in early breast cancer.

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Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
27
issue
3
pages
10 pages
publisher
American Association for Cancer Research
external identifiers
  • pmid:33148672
  • scopus:85100333321
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-20-3299
language
English
LU publication?
yes
id
0f0ec2dd-512c-4d03-ab33-5e9822e6d197
date added to LUP
2022-03-03 16:42:09
date last changed
2024-06-13 10:57:27
@article{0f0ec2dd-512c-4d03-ab33-5e9822e6d197,
  abstract     = {{<p>Purpose: Tumor-infiltrating immune cells play a key role in tumor progression. The purpose of this study was to analyze whether the immune infiltrate predicts benefit from postoperative radiotherapy in a large randomized breast cancer radiotherapy trial. Experimental Design: In the SweBCG91RT trial, patients with stage I and II breast cancer were randomized to breast-conserving surgery (BCS) and postoperative radiotherapy or to BCS only and followed for a median time of 15.2 years. The primary tumor immune infiltrate was quantified through two independent methods: IHC and gene expression profiling. For IHC analyses, the absolute stromal area occupied by CD8<sup>þ</sup> T cells and FOXP3<sup>þ</sup> T cells, respectively, was used to define the immune infiltrate. For gene expression analyses, immune cells found to be prognostic in independent datasets were pooled into two groups consisting of antitumoral and protumoral immune cells, respectively. Results: An antitumoral immune response in the primary tumor was associated with a reduced risk of breast cancer recurrence and predicted less benefit from adjuvant radiotherapy. The interaction between radiotherapy and immune phenotype was significant for any recurrence in both the IHC and gene expression analyses (P ¼ 0.039 and P ¼ 0.035) and was also significant for ipsilateral breast tumor recurrence in the gene expression analyses (P ¼ 0.025). Conclusions: Patients with an antitumoral immune infiltrate in the primary tumor have a reduced risk of any recurrence and may derive less benefit from adjuvant radiotherapy. These results may impact decisions regarding postoperative radiotherapy in early breast cancer.</p>}},
  author       = {{Tullberg, Axel Stenmark and Puttonen, Henri A.J. and Sjöström, Martin and Holmberg, Erik and Laura Chang, S. and Feng, Felix Y. and Speers, Corey and Pierce, Lori J. and Lundstedt, Dan and Killander, Fredrika and Niméus, Emma and Kovács, Anikó and Karlsson, Per}},
  issn         = {{1078-0432}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{3}},
  pages        = {{749--758}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Clinical Cancer Research}},
  title        = {{Immune infiltrate in the primary tumor predicts effect of adjuvant radiotherapy in breast cancer : Results from the randomized SweBCG91RT trial}},
  url          = {{http://dx.doi.org/10.1158/1078-0432.CCR-20-3299}},
  doi          = {{10.1158/1078-0432.CCR-20-3299}},
  volume       = {{27}},
  year         = {{2021}},
}