Detection of Minimal Residual Disease in Blood and Bone Marrow in Early Breast Cancer
S Krishnamurthy, B Singh, J Reuben, A Lodhi, M Cristofanilli, A Lucci. MD Anderson Cancer Center, Houston, TX
Background: The significance of circulating tumor cells (CTCs) in blood and disseminated tumor cells (DTCs) in bone marrow (BM) in early stage breast cancer is currently not entirely known. In this study, we investigated the occurrence of CTCs and DTCs in patient's with early stage breast cancer and evaluated the correlation of their presence with other standard prognostic markers.
Design: We collected peripheral blood before surgery and BM aspirates (from bilateral iliac crests) at the time of primary breast surgery. CTCs were detected by immunomagnetic's (Cell Search, Veridex, LLC) using 3 tubes, each containing 7.5 ml of blood. Presence of one or more CTCs in either tube was considered as positive. The BM aspirates were subjected to Ficoll Hypaque density gradient separation and 10 cytospins which were immunstained using pancytokeratin antibody (cocktail of AE1/AE3, CAM5.2, MNF116,CK8,CK18). The presence of any cytokeratin(CK) positive cell/cells with morphological features consistent with tumor cells was regarded as positive for DTC. The presence of CTCs in blood and DTCs in BM was correlated with standard prognostic markers including tumor stage (T1 vs T2), lymph node status, estrogen, progesterone receptor, and HER2 status of the primary tumor.
Results: The study included 92 patients belonging to stage T1(49) and T2 (43). CTCs were detected in 25 of 81 (31%) and DTCs in 18 of 67 (27%) patients. CTCs and DTCs were nearly equally prevalent in the lymph node(LN) positive and LN negative groups; DTCs in 8 of 31 LN + vs 10 of 36 LN- (P=0.856): CTCs in 10 of 25 LN+ vs 15 of 46 LN- group (p=0.657). Similarly, CTCs were detected in 12 of 43 stage T1 vs 12 of 46 stage T2, in 18/54 ER + vs 7/27 ER-, in 14/45 PR+ vs 11/37 PR-, in 1/4 HER2+ vs 24/77 HER2 patients respectively. DTCs were detected in 11/36 stage T1 vs 6/29 stage T2, in 11/48 ER+ vs 7/19 ER-, in 8/36 PR+ vs 10/31 PR-, 0/4 HER2+ vs 18/63 HER- patients respectively. There was no significant correlation between the occurrence of CTCs in blood and DTCs in BM with tumor stage (T1 vsT2), ER, PR and HER2 positivity.
Conclusions: 1).CTCs and DTCs in blood and bone marrow occurred in 31% and 27% of patients with T1 and T2 breast cancer.2)The presence of minimal residual disease in blood and BM did not correlate with other prognostic indicators including lymph node positivity, tumor stage, ER, PR status or HER2 overexpression.3)The lack of correlation with lymph node positivity indicates independent modes of dissemination of the tumor cells to these homing sites.
Tuesday, March 10, 2009 9:00 AM
Platform Session: Section B, Tuesday Morning