Supplementary MethodsTable S5. Clinical characteristics of the Sjöström and Servant cohortsTable S6. Comparison of included versus excluded patientsTable S7. 10-year follow-up for local recurrence (IBTR). Flexible parametric survival analysis with Royston-Parmar (RP) regression models used in Figures 2 and 3Table S8. 10-year follow-up for local recurrence (IBTR). Flexible parametric survival analysis with Royston-Parmar (RP) regression models with adjustment for other covariatesTable S9. Absolute number of events within different tertiles of Immunescore and Proliferative Index and depending on RT treatmentTable S10. Unadjusted and adjusted analysis of the interaction between the Integrated model and RT in the SweBCG91RT cohortTable S11. Distribution of subtypes in the tertiles of the Integrated score among high-risk patients
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.
