Prognostic significance of the immunocytochemical detection of contaminating tumor cells (CTC) in apheresis products of patients with high-risk breast cancer treated with high-dose chemotherapy and stem cell transplantation

Abstract

Summary:The aim of this study was to determine whether the detection of CTC in the apheresis product contribute significantly to treatment failure of patients with highrisk breast carcinoma treated with high-dose chemotherapy (HDC) and stem cell transplantation (SCT). Patients were with stage II and III adenocarcinoma of the breast with у10 axillary lymph nodes affected after primary surgery (у10 N+) who had received HDC with SCT. We analyzed retrospectively the presence of CTC as assessed by immunocytochemistry (ICC) in the apheresis products obtained after standard adjuvant chemotherapy. We compared the clinical outcome of patients who received HDC and SCT with or without CTC-positive apheresis. One hundred and twenty-seven apheresis products samples were obtained from 51 patients. Fourteen (27.4%) of these samples were CTC positive. After a median follow-up of 4.6 years, 20 patients have relapsed, 14 died from progression of their disease and 30 patients remain alive and free of progression. For the whole group of patients the 5 year probabilities of DFS and OS were 60% (IC 95%, 47-75%) and 71% (IC 95%, 55-83%), respectively. However, the 5 year probabilities of DFS were 23% (IC 95%, 0-46) and 75% (IC 95%, 60-89) for patients with CTC positive and negative, respectively. The 5 year probabilities of OS were 42% (IC 95%, 15-68) and 83% (IC 95%, 70-95) for patients with CTC positive and negative, respectively. Both univariate and multivariate analysis showed that the presence of CTC in the apheresis product was the only prognostic factor associated with a higher incidence of clinically overt disease relapse (P = 0.002) and shorter survival (P = 0.003). The presence of cytokeratin-positive metastatic cells in the apheresis product increases the risk of relapse after HDC and SCT in patients with stage II and III adeno- High-dose chemotherapy (HDC) with stem cell transplantation (STC) has been extensively used to treat women with breast cancer based on phase II studies suggesting a clinical benefit in some groups of patients with metastatic, 1-6 and high-risk breast cancer (HRBC). 7-11 However, preliminary results from most 12,13 but not all 14 phase III trials in HRBC patients, suggest no benefit for HDC over conventional treatment. Until the results from currently ongoing phase III trials determine the role of this therapy in patients with breast cancer, identification of new prognostic factors associated with an increased risk of relapse after HDC and SCT may help to define better which patients may benefit from this approach. A number of recent studies have implicated the presence of micrometastatic breast cancer cells in the bone marrow (BM) as an important and independent prognostic factor for relapse after standard chemotherapy. [15][16][17][18][19] Some studies have suggested a relation between the presence of CTC in the apheresis and relapse after HDC and SCT while other studies, mainly in patients with metastatic disease, have not been able to demonstrate such a relationship. [20][21][22] The aim of our s...

Immunomagnetic Tumor Cell Enrichment Is Promising in Detecting Circulating Breast Cancer Cells

“…The failure to identify circulating breast cancer cells in patients with early-stage disease can lead to an improper therapy strategy, which can cause the recurrence of breast cancer [7, 8]. It can also cause the reinfusion of tumor cells, since peripheral blood stem cells for hematopoietic reconstitution are necessary in some breast cancer patients [7, 8]. Nevertheless, the quantification of these cells is extremely difficult because of the low frequency of these cells in blood [9, 10].…”

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study

“…The patients in our series were mobilized during the recovery from induction cycles, when active metastatic disease was still present and the risk of contamination would theoretically be higher. Although the actual prognostic significance of contaminating tumor cells remains controversial, [24][25][26][27] we considered it appropriate to infuse an unselected cellular product immediately after the next one or two courses following collection, but not at a later time, when the tumor burden could have been markedly reduced by the treatment. In most of our patients, enough progenitors to support the whole SICT program could have been collected with a short series of leukaphereses in a single mobilization.…”

“…[24][25][26][27] Most of the experience in this area is based on the study of apheresis products collected when patients who have responded to previous induction chemotherapy are about to be intensified. The patients in our series were mobilized during the recovery from induction cycles, when active metastatic disease was still present and the risk of contamination would theoretically be higher.…”

“…Median duration of response was 12 months (95% CI, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Recurrences have been observed predominantly in areas with previous bulky disease (75% of cases).…”

The clinical significance of tumor cells in bone marrow or apheresis product and the efficacy of CD34+ selection and high‐dose chemotherapy in patients with Stage III breast cancer

“…The risk of distant recurrence is increased in patients with DTCs or CTCs [5]. It has been demonstrated that treatment with conventional [6,7] or high dose chemotherapy [8] in patients with breast cancer may reduce the number of DTCs/ CTCs and that relapse free survival is longer in patients without CTCs [8][9][10] Although it has been shown that the contamination of tumor cells in autologous grafts are responsible in posttransplant relapses, [11,12] the clinical significance of this finding is not known. The other way of reducing CTCs in autologous grafts is CD34 1 cell selection [13,14].…”