Comprehensive multiplexed immune profiling of the ductal carcinoma in situ immune microenvironment regarding subsequent ipsilateral invasive breast cancer risk.
IF: 9.075
Cited by: 3


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. 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). 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. 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.




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