Abstract PD04-01: Does Analysis of Disseminated Tumor Cells in Bone Marrow Give Additional Prognostic Information in Primary Breast Cancer? Analysis of Disseminated Tumor Cells in Bone Marrow — Report of a Prospective Study with 5 Years Follow-Up

Abstract

Abstract Introduction: Disseminated tumor cells (DTC) in bone marrow of patients with breast cancer has, beyond the formerly known and clinically used prognostic markers, in recent publications been identified as an independent predictor of poor prognosis in patients with non-metastatic disease. Detection of DTC could therefore be a way to identify patients with an increased risk of recurrence among patients with a “good” standard prognostic profile. The present prospective study aimed to evaluate the presence and prognostic value of DTC in bone marrow in women undergoing surgery for primary breast cancer. Material and methods: From 1999 to 2003 bone marrow aspirates were obtained from the sternal crest in 569 patients during surgery for primary invasive breast cancer. Tumor cells in bone marrow were identified with cytokeratins (4,5,6,7,8,10,13,14,15,16,18,19) against epithelial cells and analyzed with immunofluorescence and immunohistochemistry. The results were related to clinical follow up for 5 years using distant disease free survival (DDFS) and breast cancer specific survival (BCSS) as end-points by uni-and multivariate analysis including standard prognostic factors. Results: Analysis of DTC were performed in 445 patients and cytokeratin positive cells were found in 159 of these (36%). The presence of DTC in bone marrow was not related to lymph node metastases (N+ 38% vs N-35%, p= 0.4), ER+/ER-(38% vs 30%, p= 0.2) or histological grade (40% grade 1; 37% grade 2; 30% grade 3, p= 0.18). BCSS was related to: lymph node engagement (+ vs -; HR 3.5, p< 0.001), ER (+ vs -; HR 0.55, p= 0.046), histological grade (2 vs 1: HR 4.9, p= 0.03; 3 vs 1: HR 7.4, p= 0.008), age (HR 1.02/year, p= 0.04) and tumor size (>20 mm vs <20 mm: HR 1.8, p= 0.05) in Cox multivariate analysis. Presence of DTC did not correlate either with DDFS (p= 0.97) or BCSS (p= 0.75). In the subgroup N0/ER-, a significantly higher rate of distant metastases was observed in patients with micrometastases in bone marrow (2/12 vs 0/25; p= 0.04; log rank test) and BCSS in the same subgroup was significantly related to the presence of DTC in bone marrow (2/12 vs 0/25; p= 0.04). Conclusion: Detection of micrometastases in bone marrow in primary breast cancer has previously been shown to be a significant independent predictor of poor prognosis in different studies. In a consecutive cohort including unselected patients we were not able to confirm these results. Our data suggest that it is too early to implement the method of bone marrow aspiration and diagnosis of DTC in clinical routine. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-01.