Minimal Residual Disease in Blood and Bone Marrow in Lymph Node Negative Early Stage Breast Cancer.
Savitri Krishnamurthy, Ashutosh Lodhi, Carolyn Hall, Summer Jackson, Amber Anderson, Anirbhan Bhattacharya, Balraj Singh, Anthony Lucci. MD Anderson Cancer Center, Houston, TX
Background: There is currently tremendous interest in standardizing the detection of circulating tumor cells (CTCs) in peripheral blood and disseminated tumor cells (DTCs) in bone marrow (BM) and in understanding the implications of their detection in breast cancer. We undertook this study to evaluate the occurrence of CTCs and DTCs in node negative early stage breast cancer and to correlate their presence with currently utilized standard prognostic and predictive indicators.
Design: Peripheral blood and BM aspirations were collected from patients with early stage breast cancer and tested for CTCs by the Cell search test (Veridex) and for DTCs using pancytokeratin immunostains of 10 cytospins of BM aspirates enriched by density gradient method. The presence of any CTCs and DTCs was correlated with tumor type, tumor grade, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2(HER2) and with the Oncotype Dx Recurrence score (RS).
Results: A total of 132 patients (112 invasive ductal (IDC), 13 invasive lobular(ILC) and 7 other types) were studied. We detected CTCs in 35/132(27%) and DTCs in 34/107(32%) of the patients. CTCs occurred independent of DTCs in 88% of the patients and together in only 10% (p=0.8). CTCs occurred significantly more in high grade tumors; 35% vs 23% in intermediate and in 15% low grade tumors (p=0.04) and in ILCs compared to IDCs; 54% vs 33% (p=0.05). CTCs were noted in 26% ER+ vs 28% ER-, 23% PR+ vs 26% PR- and in 31% HER2+ vs 26% HER2- patients. DTCs were equally prevalent in low (42%), intermediate(35%) and high (23%) grade tumors and in IDCs (33%) and ILCs (30%). DTCs were noted in 34% ER+ vs 24% ER -, 32%PR+ vs 31% PR- and in 25% HER2+ vs 33% HER2- tumors. Oncotype DX testing was performed in 32 ER+ patients in whom CTCs and DTCs were detected in 17% and 40% with low, 50% and 50% with intermediate and in 25% and 33% with RS. There was no correlation between CTCs and DTCs with ER,PR,HER2 and with RS of primary tumor.
Conclusions: 1. Patients with node negative early stage breast cancer had CTCs significantly more often in high histologic grade invasive tumors and in those of lobular phenotype. 2. CTCs and DTCs did not correlate with ER, PR and HER2 status and with RS of the primary tumor. 3. The lack of correlation of the occurrence of CTCs and DTCs suggests independent modes of dissemination to blood and bone marrow. 4. The implications of our findings in this population needs to be validated in larger prospective multi-institutional clinical trials.
Tuesday, March 1, 2011 9:00 AM
Platform Session: Section C, Tuesday Morning