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

Aglaia Schiza; Viktoria Thurfjell; Axel Stenmark Tullberg; Helena Olofsson; Amanda Lindberg; Erik Holmberg; Troy Bremer; Patrick Micke; Per Karlsson; Fredrik Wärnberg; Carina Strell

doi:10.1016/j.ejca.2022.01.016

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

Eur J Cancer. 2022 Jun:168:128-137. doi: 10.1016/j.ejca.2022.01.016. Epub 2022 Feb 27.

Affiliations

¹ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
² Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
³ Department of Pathology, Centre for Clinical Research of Uppsala University, Vastmanland´s Hospital Vasterås, Sweden.
⁴ PreludeDx, Laguna Hills, CA, USA.
⁵ Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Electronic address: carina.strell@igp.uu.se.

PMID: 35236568
DOI: 10.1016/j.ejca.2022.01.016

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.

Keywords: Ductal carcinoma in situ; Radiotherapy; Ttumour infiltrating lymphocytes.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / pathology
Breast Neoplasms* / radiotherapy
Breast Neoplasms* / surgery
Carcinoma, Intraductal, Noninfiltrating* / radiotherapy
Carcinoma, Intraductal, Noninfiltrating* / surgery
Female
Humans
Lymphocytes, Tumor-Infiltrating
Mastectomy, Segmental
Neoplasm Recurrence, Local / pathology
Prognosis
Tumor Microenvironment