Comprehensive Multiplexed Immune Profiling of the Ductal Carcinoma In Situ Immune Microenvironment Regarding Subsequent Ipsilateral Invasive Breast Cancer Risk

Authors

Mathilde M Almekinders
Tycho Bismeijer
Tapsi Kumar
Fei Yang
Bram Thijssen
Rianne van der Linden
Charlotte van Rooijen
Shiva Vonk
Baohua Sun
Edwin R Parra Cuentas
Ignacio I Wistuba
Savitri Krishnamurthy
Lindy L Visser
Iris M Seignette
Ingrid Hofland
Joyce Sanders
Annegien Broeks
Jason K Love
Brian Menegaz
Lodewyk Wessels
Alastair M Thompson
Karin E de Visser
Erik Hooijberg
Esther Lips
Andrew Futreal
Jelle Wesseling

Publication Date

10-1-2022

Journal

British Journal of Cancer

Abstract

Background: Ductal carcinoma in situ (DCIS) is treated to prevent subsequent ipsilateral invasive breast cancer (iIBC). However, many DCIS lesions will never become invasive. To prevent overtreatment, we need to distinguish harmless from potentially hazardous DCIS. We investigated whether the immune microenvironment (IME) in DCIS correlates with transition to iIBC.

Methods: Patients were derived from a Dutch population-based cohort of 10,090 women with pure DCIS with a median follow-up time of 12 years. Density, composition and proximity to the closest DCIS cell of CD20+ B-cells, CD3+CD8+ T-cells, CD3+CD8- T-cells, CD3+FOXP3+ regulatory T-cells, CD68+ cells, and CD8+Ki67+ T-cells was assessed with multiplex immunofluorescence (mIF) with digital whole-slide analysis and compared between primary DCIS lesions of 77 women with subsequent iIBC (cases) and 64 without (controls).

Results: Higher stromal density of analysed immune cell subsets was significantly associated with higher grade, ER negativity, HER-2 positivity, Ki67 ≥ 14%, periductal fibrosis and comedonecrosis (P < 0.05). Density, composition and proximity to the closest DCIS cell of all analysed immune cell subsets did not differ between cases and controls.

Conclusion: IME features analysed by mIF in 141 patients from a well-annotated cohort of pure DCIS with long-term follow-up are no predictors of subsequent iIBC, but do correlate with other factors (grade, ER, HER2 status, Ki-67) known to be associated with invasive recurrences.

Keywords

Biomarkers, Tumor, Breast Neoplasms, CD8-Positive T-Lymphocytes, Carcinoma, Ductal, Breast, Carcinoma, Intraductal, Noninfiltrating, Female, Forkhead Transcription Factors, Humans, Ki-67 Antigen, Tumor Microenvironment

DOI

10.1038/s41416-022-01888-2

PMID

35768550

PMCID

PMC9519539

PubMedCentral® Posted Date

6-29-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes