Abstract

Abstract Background Recently it was shown that tumor cell dissemination is an early event in breast cancer progression (Hosseini et al., Nature 2016). This has been backed up by an assessment of over 100,000 patients with in situ carcinoma (DCIS), where some patients developed distant metastases and died from breast cancer without presenting with local invasive recurrence (Narod et al., JAMA Oncology 2015). We therefore analyzed the presence and clinical impact of disseminated tumor cells (DTC) in the bone marrow (BM) of DCIS patients. Methods BM aspirates were collected from patients undergoing surgery for primary DCIS at Tuebingen University Hospital between 2001 and 2016. Exclusion criteria were presence of invasive breast cancer, bilateral or metastatic disease as well as other malignancies in their history. DTC were identified by immunocytochemistry using the A45-B/B3 anti-pancytokeratin antibody. Results 627 patients were included. Median follow-up was 49 months. 72 (11%) had detectable DTC. The detection of DTC was not significantly associated with lymph node positivity (3/479, Fisher's exact test: p=0.307) or tumor size (median 30mm, Wilcoxon test: p=0.952). In 33 (5%) women, a disease recurrence was observed. Of 31 local recurrences 19 were invasive. 7 Patients developed distant metastases, four without an invasive recurrence beforehand. 14 patients died during follow-up. The detection of at least 2 DTC per 1.5x106 mononuclear BM cells was significantly associated with a lower local recurrence free survival (log-rank: p=0.023) whereas there was no significant difference in distant disease free survival (p=0.315) and overall survival (p=0.083). Discussion For the first time, we were able to show that DTC-detection in DCIS patients is associated with local recurrence. The number of distant metastases in women without invasive local recurrence detected in this cohort was comparable to earlier findings at different centers. This study warrants further investigations concerning evolutionary relationship between primary tumor, minimal residual disease, local recurrence and clinically detectable macrometastases. Citation Format: Walter VP, Taran F-A, Wallwiener M, Brucker SY, Hartkopf AD. Detection of disseminated tumor cells in DCIS patients impacts local recurrence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-16.

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