Abstract 2332: Ductal carcinoma in situ: Potential to metastasize? A nationwide cancer registry-based study

Abstract Background: The current clinical paradigm around Ductal Carcinoma in Situ (DCIS) is that it consists of malignant cells confined to the breast ducts, and therefore cannot metastasize. Nonetheless, several studies have reported DCIS with metastasis in the sentinel lymph node (SN+). For accurate risk communication and management, we aimed to assess to what extent registered “metastatic spread” in DCIS could be explained by limitations in registration or missed invasive breast cancer at time of diagnosis. Methods: Data from the nationwide cancer registry and national pathology database on women diagnosed with DCIS SN+ in the Netherlands, spanning from 2005 to 2020, was curated and reviewed, taking into account their histories of prior DCIS, invasive breast cancer, or other malignancies. Cases were excluded from further analysis if pathology data indicated registration errors, DCIS mixed with other lesion types, or diagnostic uncertainties. Next, hematoxylin and eosin-stained tissue slides of eligible DCIS SN+ cases were independently reviewed by two pathologists to assess the presence of invasive breast cancer and SN status. Additional immunohistochemical staining (CK 5/6 or CK 8/18) was performed when findings were unclear. Inter-observer agreement was evaluated using the linearly weighted Kappa statistic. Results: A total of 30, 863 patients were identified with a DCIS diagnosis between 2005 and 2020, of which 16, 070 (52%) underwent SN biopsy according to cancer registry data. SN+ was registered in 454 (3 %) patients: 47 (10%) had macrometastases (>2 mm), 78 (17%) had micrometastases (>0.2 to <= 2 mm), and 329 (73%) were positive for isolated tumor cells (<= 0.2 mm). Out of the 454 registered DCIS SN+ cases, 273 (60%) were excluded from further investigation based on pathology data, including registration errors (n=44), DCIS mixed with other lesions (n=147), and diagnostic uncertainties (n=82). Tissue material of 46 (37%) out of 125 registered cases with macro- and micrometastases was reviewed. Observer variability in assessing the presence of invasive breast cancer was high (k= 0.14; 95% CI 0.08 - 0.34; p = 0.12) and additional CK 5/6 staining was requested for 38 cases. Two cases were classified as primary invasive breast cancer, 25 as pure DCIS, while 19 remained inconclusive, due to variation in tissue sections or suboptimal tissue quality. In six cases the SN was scored as negative by pathology revision, likely due to tissue section variability. Conclusions: Our study indicates that DCIS in itself has minimal to no metastatic potential. Ongoing clonality analysis of 9 cases with macrometastases aims to determine whether the SN metastases are clonally related to the DCIS lesions. Citation Format: Merle van Leeuwen, Sandra van den Belt- Dusebout, Petra Kristel, Lennart Mulder, Joyce Sanders, Carmen Vlahu, Esther H. Lips, Jelle Wesseling. Ductal carcinoma in situ: Potential to metastasize? A nationwide cancer registry-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2332.