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Rich66 · 09-24-2009, 10:52 AM

Although a tad controversial, Circulating tumor cell test (CTC), (maybe DTC as well) could be useful:

1: Am J Clin Pathol. 2009 Aug;132(2):237-45.

Links

Circulating and disseminated tumor cells in the management of breast cancer.

Ross JS, Slodkowska EA.
Department of Pathology and Laboratory Medicine, Mail Code 81, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208, USA.
Despite the advances in early detection and treatment of cancer, patients continue to die of the disease even when they seek care at an early stage. For patients with breast cancer, it is now possible to detect circulating tumor cells (CTCs) in the bloodstream and disseminated tumor cells (DTCs) in the bone marrow by using immunocytochemical and molecular methods. CTCs and DTCs have been found to share similar genotypic and phenotypic characteristics with so-called breast cancer stem cells, a finding that could potentially explain the eventual relapse of disease in a patient previously considered to have been cured by primary therapy. In some studies, the presence of CTCs or DTCs at the time of diagnosis of breast cancer is an independent adverse prognostic variable. However, before CTC/DTC testing can achieve standard-of-care status, there must be improvement in the sensitivity, precision, and reproducibility of the detection methods.
PMID: 19605818 [PubMed - indexed for MEDLINE]
1: Ann Oncol. 2008 Mar;19(3):496-500. Epub 2008 Jan 10.

Links

Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells.

Bidard FC, Vincent-Salomon A, Sigal-Zafrani B, Diéras V, Mathiot C, Mignot L, Thiery JP, Sastre-Garau X, Pierga JY.
Department of Medical Oncology, Institut Curie, Paris, France.
BACKGROUND: At metastatic relapse, detection of circulating tumor cells (CTC) in peripheral blood is predictive of poor survival of breast cancer patients. Detection of disseminated tumor cells (DTC) in bone marrow (BM) is an independent prognostic factor in early breast cancer. We evaluated the prognostic value of DTC detection in the BM of metastatic breast cancer patients. MATERIALS AND METHODS: BM aspirates from 138 patients were screened for DTC with the pancytokeratin mAb A45-B/B3, according to the ISHAGE classification. One hundred and ten patients (80%) were enrolled before first-line treatment. Thirty-seven patients were simultaneously screened for CTC in the blood. RESULTS: DTC detection rate in the BM was 59%. DTC were associated with bone metastasis (P = 0.0001), but not with a poorer overall survival. Adverse significant prognostic factors were hormone receptor negativity (P = 0.0004) and more than one line of chemotherapy (P = 0.002). CTC detection in the subgroup of 37 metastatic patients was associated with shorter survival (P = 0.01). CONCLUSIONS: Detection of CTC but not BM DTC had a prognostic significance in stage IV breast cancer patients. CTC in blood are a more reliable and a less invasive tool to evaluate prognostic and monitor tumor response in this metastatic setting.
PMID: 18187488 [PubMed - indexed for MEDLINE]
Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells.

Sieuwerts AM, Kraan J, Bolt J, van der Spoel P, Elstrodt F, Schutte M, Martens JW, Gratama JW, Sleijfer S, Foekens JA.
Department of Medical Oncology, Josephine Nefkens Institute, Cancer Genomics Centre, Rotterdam, the Netherlands. a.sieuwerts@erasmusmc.nl
Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five subtypes of human breast cancer cells that have been defined by global gene expression profiling-normal-like, basal, HER2-positive, and luminal A and B-were identified by CellSearch, a US Food and Drug Administration-approved test that uses antibodies against the cell surface-expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor cells. We used global gene expression profiling to determine the subtypes of a well-defined panel of 34 human breast cancer cell lines (15 luminal, nine normal-like, five basal-like, and five Her2-positive). We mixed 50-150 cells from 10 of these cell lines with 7.5 mL of blood from a single healthy human donor, and the mixtures were subjected to the CellSearch test to isolate the breast cancer cells. We found that the CellSearch isolation method, which uses EpCAM on the surface of circulating tumor cells for cell isolation, did not recognize, in particular, normal-like breast cancer cells, which in general have aggressive features. New tests that include antibodies that specifically recognize normal-like breast tumor cells but not cells of hematopoietic origin are needed.

09-24-2009, 10:52 AM	#7
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: What questions should I be asking Although a tad controversial, Circulating tumor cell test (CTC), (maybe DTC as well) could be useful: 1: Am J Clin Pathol. 2009 Aug;132(2):237-45. Links Circulating and disseminated tumor cells in the management of breast cancer. Ross JS, Slodkowska EA. Department of Pathology and Laboratory Medicine, Mail Code 81, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208, USA. Despite the advances in early detection and treatment of cancer, patients continue to die of the disease even when they seek care at an early stage. For patients with breast cancer, it is now possible to detect circulating tumor cells (CTCs) in the bloodstream and disseminated tumor cells (DTCs) in the bone marrow by using immunocytochemical and molecular methods. CTCs and DTCs have been found to share similar genotypic and phenotypic characteristics with so-called breast cancer stem cells, a finding that could potentially explain the eventual relapse of disease in a patient previously considered to have been cured by primary therapy. In some studies, the presence of CTCs or DTCs at the time of diagnosis of breast cancer is an independent adverse prognostic variable. However, before CTC/DTC testing can achieve standard-of-care status, there must be improvement in the sensitivity, precision, and reproducibility of the detection methods. PMID: 19605818 [PubMed - indexed for MEDLINE] 1: Ann Oncol. 2008 Mar;19(3):496-500. Epub 2008 Jan 10. Links Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells. Bidard FC, Vincent-Salomon A, Sigal-Zafrani B, Diéras V, Mathiot C, Mignot L, Thiery JP, Sastre-Garau X, Pierga JY. Department of Medical Oncology, Institut Curie, Paris, France. BACKGROUND: At metastatic relapse, detection of circulating tumor cells (CTC) in peripheral blood is predictive of poor survival of breast cancer patients. Detection of disseminated tumor cells (DTC) in bone marrow (BM) is an independent prognostic factor in early breast cancer. We evaluated the prognostic value of DTC detection in the BM of metastatic breast cancer patients. MATERIALS AND METHODS: BM aspirates from 138 patients were screened for DTC with the pancytokeratin mAb A45-B/B3, according to the ISHAGE classification. One hundred and ten patients (80%) were enrolled before first-line treatment. Thirty-seven patients were simultaneously screened for CTC in the blood. RESULTS: DTC detection rate in the BM was 59%. DTC were associated with bone metastasis (P = 0.0001), but not with a poorer overall survival. Adverse significant prognostic factors were hormone receptor negativity (P = 0.0004) and more than one line of chemotherapy (P = 0.002). CTC detection in the subgroup of 37 metastatic patients was associated with shorter survival (P = 0.01). CONCLUSIONS: Detection of CTC but not BM DTC had a prognostic significance in stage IV breast cancer patients. CTC in blood are a more reliable and a less invasive tool to evaluate prognostic and monitor tumor response in this metastatic setting. PMID: 18187488 [PubMed - indexed for MEDLINE] Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells. Sieuwerts AM, Kraan J, Bolt J, van der Spoel P, Elstrodt F, Schutte M, Martens JW, Gratama JW, Sleijfer S, Foekens JA. Department of Medical Oncology, Josephine Nefkens Institute, Cancer Genomics Centre, Rotterdam, the Netherlands. a.sieuwerts@erasmusmc.nl Identification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all tumor cell types. We investigated whether the five subtypes of human breast cancer cells that have been defined by global gene expression profiling-normal-like, basal, HER2-positive, and luminal A and B-were identified by CellSearch, a US Food and Drug Administration-approved test that uses antibodies against the cell surface-expressed epithelial cell adhesion molecule (EpCAM) to isolate circulating tumor cells. We used global gene expression profiling to determine the subtypes of a well-defined panel of 34 human breast cancer cell lines (15 luminal, nine normal-like, five basal-like, and five Her2-positive). We mixed 50-150 cells from 10 of these cell lines with 7.5 mL of blood from a single healthy human donor, and the mixtures were subjected to the CellSearch test to isolate the breast cancer cells. We found that the CellSearch isolation method, which uses EpCAM on the surface of circulating tumor cells for cell isolation, did not recognize, in particular, normal-like breast cancer cells, which in general have aggressive features. New tests that include antibodies that specifically recognize normal-like breast tumor cells but not cells of hematopoietic origin are needed.