PMID- 35768550 OWN - NLM STAT- In-Process VI - 127 IP - 7 TI - Comprehensive multiplexed immune profiling of the ductal carcinoma in situ immune microenvironment regarding subsequent ipsilateral invasive breast cancer risk. PG - 1201-1213 CI - © 2022. The Author(s). LA - eng PT - Journal Article PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 IS - 1532-1827 (Electronic) LID - 10.1038/s41416-022-01888-2 [doi] FAU - Almekinders, Mathilde M AU - Almekinders MM AUID- ORCID: http://orcid.org/0000-0002-1554-2887 AD - Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. AD - Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. AD - Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. FAU - Bismeijer, Tycho AU - Bismeijer T AUID- ORCID: http://orcid.org/0000-0001-6514-4767 AD - Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands. FAU - Kumar, Tapsi AU - Kumar T AUID- ORCID: http://orcid.org/0000-0003-2825-3387 AD - Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX, USA. AD - Department of Genetics, MD Anderson Cancer Center, Houston, TX, USA. AD - MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX, USA. FAU - Yang, Fei AU - Yang F AD - Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX, USA. FAU - Thijssen, Bram AU - Thijssen B AUID- ORCID: http://orcid.org/0000-0003-1562-2649 AD - Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands. FAU - van der Linden, Rianne AU - van der Linden R AD - Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. FAU - van Rooijen, Charlotte AU - van Rooijen C AD - Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. FAU - Vonk, Shiva AU - Vonk S AD - Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. AD - Core Facility Molecular Pathology and Biobanking, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. FAU - Sun, Baohua AU - Sun B AD - Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX, USA. FAU - Parra Cuentas, Edwin R AU - Parra Cuentas ER AUID- ORCID: http://orcid.org/0000-0001-9068-1636 AD - Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX, USA. FAU - Wistuba, Ignacio I AU - Wistuba II AD - Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, TX, USA. FAU - Krishnamurthy, Savitri AU - Krishnamurthy S AD - Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA. FAU - Visser, Lindy L AU - Visser LL AUID- ORCID: http://orcid.org/0000-0001-7856-1981 AD - Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. FAU - Seignette, Iris M AU - Seignette IM AD - Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. FAU - Hofland, Ingrid AU - Hofland I AD - Core Facility Molecular Pathology and Biobanking, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. FAU - Sanders, Joyce AU - Sanders J AUID- ORCID: http://orcid.org/0000-0002-0551-7813 AD - Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. FAU - Broeks, Annegien AU - Broeks A AD - Core Facility Molecular Pathology and Biobanking, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. FAU - Love, Jason K AU - Love JK AD - Breast Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA. FAU - Menegaz, Brian AU - Menegaz B AUID- ORCID: http://orcid.org/0000-0002-3020-5790 AD - Department of Surgery, Baylor College of Medicine, Houston, TX, USA. FAU - Wessels, Lodewyk AU - Wessels L AD - Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands. AD - Oncode Institute, Utrecht, The Netherlands. FAU - Thompson, Alastair M AU - Thompson AM AD - Division of Surgical Oncology, Baylor College of Medicine, Houston, TX, USA. FAU - de Visser, Karin E AU - de Visser KE AD - Oncode Institute, Utrecht, The Netherlands. AD - Division of Tumour Biology & Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands. AD - Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands. FAU - Hooijberg, Erik AU - Hooijberg E AD - Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. FAU - Lips, Esther AU - Lips E AUID- ORCID: http://orcid.org/0000-0003-3488-4935 AD - Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. FAU - Futreal, Andrew AU - Futreal A AUID- ORCID: http://orcid.org/0000-0001-8663-2671 AD - Department of Genomic Medicine, MD Anderson Cancer Center, Houston, TX, USA. FAU - Wesseling, Jelle AU - Wesseling J AUID- ORCID: http://orcid.org/0000-0002-8940-2676 AD - Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands. j.wesseling@nki.nl. AD - Department of Pathology, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. j.wesseling@nki.nl. AD - Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. j.wesseling@nki.nl. CN - Grand Challenge PRECISION Consortium IS - 0007-0920 (Linking) SB - IM LR - 20220929 DP - 2022 Oct DEP - 20220629 AB - 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.