Tumour-infiltrating lymphocytes add prognostic information for patients with low-risk DCIS: findings from the SweDCIS randomised radiotherapy trial. (June 2022)

• Record Type: Journal Article
• Authors: Schiza, Aglaia; Thurfjell, Viktoria; Stenmark Tullberg, Axel; Olofsson, Helena; Lindberg, Amanda; Holmberg, Erik; Bremer, Troy; Micke, Patrick; Karlsson, Per; Wärnberg, Fredrik; Strell, Carina
• Is Part Of: European journal of cancer. Volume 168(2022)
• Page Start: 128
• Page End: 137
• Publication Date: 2022-06
• Subjects: Ductal carcinoma in situ -- Ttumour infiltrating lymphocytes -- Radiotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.01.016
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: 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 low -versus TILs high 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. Highlights: High tumour-infiltrating lymphocytes (TILs) are associated with a higher recurrence risk in human epidermal growth factor receptor 2 -negative ductal carcinoma in situ (DCIS). TILs can refine the assignment of patients with low-risk DCIS to adjuvant radiotherapy. TILs do not impact radiotherapy efficacy in DCIS.