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Study protocol S1 from Integrating Tumor-Intrinsic and Immunologic Factors to Identify Immunogenic Breast Cancers from a Low-Risk Cohort: Results from the Randomized SweBCG91RT Trial

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posted on 2023-05-01, 08:20 authored by Axel Stenmark Tullberg, Martin Sjöström, Emma Niméus, Fredrika Killander, S. Laura Chang, Felix Y. Feng, Corey W. Speers, Lori J. Pierce, Anikó Kovács, Dan Lundstedt, Erik Holmberg, Per Karlsson

Protocol for original SweBCG91RT trial

Funding

Cancerfonden (Swedish Cancer Society)

Stiftelsen Konung Gustaf V:s Jubileumsfond (King Gustaf V's Jubilee Foundation)

ALF agreement

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ARTICLE ABSTRACT

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. 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). 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). 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.

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