Tumour-infiltrating lymphocytes add prognostic information for patients with low-risk DCIS: findings from the SweDCIS randomised radiotherapy trial.

BACKGROUND

The immune microenvironment is an important modulator of tumour progression and treatment response. In invasive breast cancer, assessment of tumour-infiltrating lymphocytes (TILs) provides prognostic and predictive information. However, the clinical impact of TILs for ductal carcinoma in situ (DCIS) has not yet been demonstrated.

PATIENTS AND METHODS

Post hoc analysis of the SweDCIS randomised radiotherapy trial including primary DCIS cases following breast-conserving surgery. TILs were assessed on haematoxylin-eosin sections (n = 711) according to the International Immuno-Oncology Biomarker Working Group guidelines. TILs-scores were analysed as continuous and dichotomised (≤5% versus >5%) variable regarding ipsilateral breast events (IBEs) as the predefined primary endpoint.

RESULTS

Most women (61.9%) showed a TILs prevalence of ≤5%. High TILs-scores were associated with larger lesion size, human epidermal growth factor receptor 2 (HER2)-positivity, higher nuclear grade, and KI67-score. DCIS cases with high TILs prevalence had a significant increased cumulative IBE incidence at five years post-surgery (TILs-versus TILs 9% versus 18%; p < 0.001). Among patients with HER2-negative DCIS, high TILs remained an independent poor prognosis marker for IBE risk in multivariable analysis with an adjusted hazard ratio of 2.41 [95%CI 1.17-4.95, p = 0.017]. Including TILs-status provided a refined stratification of patients with general low-risk DCIS (grade <3, size <25 mm, free margin). No interaction between TILs and radiotherapy benefits was detected.

CONCLUSION

High TILs are associated with higher IBE risk over 5-years post-surgery, particularly for HER2-negative DCIS. Our data indicate that TILs should be integrated into the clinical workup to define patients with low-risk DCIS who can omit adjuvant therapy or patients with potential benefits from immunotherapy.