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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  Grand Challenge PRECISION Consortium
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.Subject terms: Prognostic markers, Imaging the immune system, Breast cancer, Cancer microenvironment, Translational research

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