The impact of immune microenvironment on local control of ductal carcinoma in situ receiving breast conservative therapy

BACKGROUND: This study aims to identify the role of tumor immune microenvironment (IME) in ductal carcinoma in situ (DCIS) in predicting benefit of whole breast irradiation (WBI). METHODS: Different subtypes of tumor infiltrating lymphocytes (TILs), tumor associated macrophages (TAMs) and tertiary lymphoid structures (TLSs) were determined in tumor tissues of DCIS cohort who received breast-conserving surgery (BCS). RESULTS: In total, 165 patients were enrolled with 113 received WBI. After a median follow-up of 73.7 months, 15 ipsilateral breast tumor recurrence (IBTR) events occurred. Nine IBTRs occurred outside of the original quadrant (elsewhere failure event, EFE). After LASSO and multivariate Cox regression analyses, the ER negative status, high ratios of CD4 + /CD8 + , dense CD68 + TAMs, sparse CD8 + T cell and dense TLSs with follicular dendritic cells (F-TLSs) remained independent risk factors of IBTR (all p < 0.05) to develop a nomogram. Points of nomogram were defined as immune microenvironment score (IMS) which divided all patients into low-, intermediate- and high-risk groups. Significant differences in IBTR existed among these three risk subgroups (5y-rate: 0.0% vs. 11.4% vs. 72.2%, p < 0.01). For the whole cohort, the benefit of WBI was found only in the intermediate-risk subgroup (5y-rate of IBTR: 7.0% vs. 22.0%, p = 0.04; EFE: 2.3% vs. 16.4%, p = 0.01) while not in the low- and high-risk group. CONCLUSIONS: Our study highlighted the assessment of overall immune cells subtypes provided a tool for comprehensive evaluation of IME in DCIS patients. The nomogram composed of biomarker and integrated IME characteristics showed the potential to stratify the risk of IBTR and predicting the benefit from WBI.