Integrating Tumor-Intrinsic and Immunologic Factors to Identify Immunogenic Breast Cancers from a Low-Risk Cohort : Results from the Randomized SweBCG91RT Trial
(2023) In Clinical cancer research : an official journal of the American Association for Cancer Research 29(9). p.1783-1793- Abstract
PURPOSE: The local immune infiltrate's influence on tumor progression may be closely linked to tumor-intrinsic factors. The study aimed to investigate whether integrating immunologic and tumor-intrinsic factors can identify patients from a low-risk cohort who may be candidates for radiotherapy (RT) de-escalation.
EXPERIMENTAL DESIGN: The SweBCG91RT trial included 1,178 patients with stage I to IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median of 15.2 years. We trained two models designed to capture immunologic activity and immunomodulatory tumor-intrinsic qualities, respectively. We then analyzed if combining these two variables could further stratify tumors, allowing... (More)
PURPOSE: The local immune infiltrate's influence on tumor progression may be closely linked to tumor-intrinsic factors. The study aimed to investigate whether integrating immunologic and tumor-intrinsic factors can identify patients from a low-risk cohort who may be candidates for radiotherapy (RT) de-escalation.
EXPERIMENTAL DESIGN: The SweBCG91RT trial included 1,178 patients with stage I to IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median of 15.2 years. We trained two models designed to capture immunologic activity and immunomodulatory tumor-intrinsic qualities, respectively. We then analyzed if combining these two variables could further stratify tumors, allowing for identifying a subgroup where RT de-escalation is feasible, despite clinical indicators of a high risk of ipsilateral breast tumor recurrence (IBTR).
RESULTS: The prognostic effect of the immunologic model could be predicted by the tumor-intrinsic model (Pinteraction = 0.01). By integrating measurements of the immunologic- and tumor-intrinsic models, patients who benefited from an active immune infiltrate could be identified. These patients benefited from standard RT (HR, 0.28; 95% CI, 0.09-0.85; P = 0.025) and had a 5.4% 10-year incidence of IBTR after irradiation despite high-risk genomic indicators and a low frequency of systemic therapy. In contrast, high-risk tumors without an immune infiltrate had a high 10-year incidence of IBTR despite RT treatment (19.5%; 95% CI, 12.2-30.3).
CONCLUSIONS: Integrating tumor-intrinsic and immunologic factors may identify immunogenic tumors in early-stage breast cancer populations dominated by ER-positive tumors. Patients who benefit from an activated immune infiltrate may be candidates for RT de-escalation.
(Less)
- author
- organization
- publishing date
- 2023-05-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Humans, Female, Breast Neoplasms/pathology, Neoplasm Recurrence, Local/pathology, Prognosis, Mastectomy, Segmental/methods, Radiotherapy, Adjuvant, Immunologic Factors/therapeutic use
- in
- Clinical cancer research : an official journal of the American Association for Cancer Research
- volume
- 29
- issue
- 9
- pages
- 1783 - 1793
- publisher
- American Association for Cancer Research Inc.
- external identifiers
-
- scopus:85159249891
- pmid:37071498
- ISSN
- 1078-0432
- DOI
- 10.1158/1078-0432.CCR-22-2746
- language
- English
- LU publication?
- yes
- additional info
- ©2023 The Authors; Published by the American Association for Cancer Research.
- id
- d3c4e092-8c20-4c15-bf8f-cd334bdc77bc
- date added to LUP
- 2026-02-19 16:31:07
- date last changed
- 2026-02-20 04:01:00
@article{d3c4e092-8c20-4c15-bf8f-cd334bdc77bc,
abstract = {{<p>PURPOSE: The local immune infiltrate's influence on tumor progression may be closely linked to tumor-intrinsic factors. The study aimed to investigate whether integrating immunologic and tumor-intrinsic factors can identify patients from a low-risk cohort who may be candidates for radiotherapy (RT) de-escalation.</p><p>EXPERIMENTAL DESIGN: The SweBCG91RT trial included 1,178 patients with stage I to IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median of 15.2 years. We trained two models designed to capture immunologic activity and immunomodulatory tumor-intrinsic qualities, respectively. We then analyzed if combining these two variables could further stratify tumors, allowing for identifying a subgroup where RT de-escalation is feasible, despite clinical indicators of a high risk of ipsilateral breast tumor recurrence (IBTR).</p><p>RESULTS: The prognostic effect of the immunologic model could be predicted by the tumor-intrinsic model (Pinteraction = 0.01). By integrating measurements of the immunologic- and tumor-intrinsic models, patients who benefited from an active immune infiltrate could be identified. These patients benefited from standard RT (HR, 0.28; 95% CI, 0.09-0.85; P = 0.025) and had a 5.4% 10-year incidence of IBTR after irradiation despite high-risk genomic indicators and a low frequency of systemic therapy. In contrast, high-risk tumors without an immune infiltrate had a high 10-year incidence of IBTR despite RT treatment (19.5%; 95% CI, 12.2-30.3).</p><p>CONCLUSIONS: Integrating tumor-intrinsic and immunologic factors may identify immunogenic tumors in early-stage breast cancer populations dominated by ER-positive tumors. Patients who benefit from an activated immune infiltrate may be candidates for RT de-escalation.</p>}},
author = {{Stenmark Tullberg, Axel and Sjöström, Martin and Niméus, Emma and Killander, Fredrika and Chang, S Laura and Feng, Felix Y and Speers, Corey W and Pierce, Lori J and Kovács, Anikó and Lundstedt, Dan and Holmberg, Erik and Karlsson, Per}},
issn = {{1078-0432}},
keywords = {{Humans; Female; Breast Neoplasms/pathology; Neoplasm Recurrence, Local/pathology; Prognosis; Mastectomy, Segmental/methods; Radiotherapy, Adjuvant; Immunologic Factors/therapeutic use}},
language = {{eng}},
month = {{05}},
number = {{9}},
pages = {{1783--1793}},
publisher = {{American Association for Cancer Research Inc.}},
series = {{Clinical cancer research : an official journal of the American Association for Cancer Research}},
title = {{Integrating Tumor-Intrinsic and Immunologic Factors to Identify Immunogenic Breast Cancers from a Low-Risk Cohort : Results from the Randomized SweBCG91RT Trial}},
url = {{http://dx.doi.org/10.1158/1078-0432.CCR-22-2746}},
doi = {{10.1158/1078-0432.CCR-22-2746}},
volume = {{29}},
year = {{2023}},
}