Lani
09-24-2006, 12:38 AM
when reading the discussion on rates of recurrence of her2+ breast cancer I found myself unable to post a graph from an article on the very high rates of recurrence of those who were found at diagnosis to have Cytokeratin+ cells in their bone marrow which also stained + for her2neu
Many papers have discussed that these are cells which are not affected by chemotherapy (according to the stem cell theory of breast cancer they are dormant cells which only very rarely divide and thus are relatively "immune" from the effects of chemotherapy) Since they stain for her2neu, they should be sensitive to herceptin, however.
When I have discussed this I have gotten three answers 1) from someone whose lab does the testing--"I don't know why not" 2) from an oncologist--
we don't want to subject our patients to that test as noone likes to have their bone marrow biopsied (!!!!!!!!!this, from someone who orders hundreds of people-- many of whom would do equally well without it, as they have been unable to test to find just those who need chemotherapy--to be given chemotherapy the effect of which lasts more than a few hours or days and which can lead to long-standing problems and increased rates of second cancers????) 3) because not all labs are good at processing the marrow and doing the test equally well although the technique protocol has been well described.
I just discovered the following, a blood test, which might help indicate those patients who should have the bone marrow tested.
Glycosyltransferase Points to Breast Cancer Metastasis
By David Douglas
NEW YORK (Reuters Health) Sept 22 - The ppGalNAc-T6 molecule, one of a family of glycosyltransferases, may be a useful marker for detection of bone marrow-disseminated breast cancer cells, Uruguayan researchers report in the September 15th issue of the International Journal of Cancer.
"Our preliminary results," lead investigator Dr. Teresa Freire told Reuters Health, "suggest that the expression of this molecule would be correlated with a worse clinical outcome of patients with breast cancer."
To investigate the utility of ppGalNAc-T6 mRNA as a marker, Dr. Freire who is currently at the Institut Pasteur, Paris and colleagues conducted a variety of tests.
mRNA was found in 22 of 25 human breast cancer samples and in all 3 human cancer cell lines examined.
In addition, ppGalNAc-T6 mRNA was found in only 1 of 30 peripheral blood mononuclear cells samples obtained from patients without cancer. None was found in bone marrow samples from this group.
Furthermore, 22 of 61 breast cancer patients showed positive bone marrow aspirates before surgery. In preliminary follow-up, 11 of these patients (57.9%) experienced recurrence.
In a subgroup of patients without lymph node involvement, 54.5% of those with positive bone marrow aspirates had recurrence. This was the case in only 4.6% of those with negative findings.
"Although further studies are necessary," continued Dr. Freire, "these results also suggest that this new potential marker could be used in combination with axillary nodal status -- the only factor used consistently as a guide for therapy -- since a high rate of disease recurrence in node-negative patients showing ppGal-NAc-T6 mRNA-positive bone marrow aspirates was observed."
Int J Cancer 2006;119:1383-1388.
I know the Germans who have been instrumental in advocating bone marrow testing are starting a clinical trial to see if directing treatment by the bone marrow results will improve prognosis...
reference for the chart on the prognosis of her2+ patients with her2+ isolated tumor cells in their bone marrow:
1: Cancer Res. 2001 Mar 1;61(5):1890-5. Links
ErbB2 overexpression on occult metastatic cells in bone marrow predicts poor clinical outcome of stage I-III breast cancer patients.
Braun S,
Schlimok G,
Heumos I,
Schaller G,
Riethdorf L,
Riethmuller G,
Pantel K.
Frauenklinik & Poliklinik, Klinikum rechts der Isar, Technische Universitat, Munchen, Germany. stephan.braun@lrz.tum.de
Occult hematogenous micrometastases are the major cause for metastatic relapse and cancer-related death in patients with operable primary breast cancer. Although sensitive immunocytochemical and molecular methods allow detection of individual breast cancer cells in bone marrow (BM), a major site of metastatic relapse, current detection techniques cannot discriminate between nonviable shed tumor cells and seminal metastatic cells. To address this problem, we analyzed the relevance of erbB2 overexpression on disseminated cytokeratin-18-positive breast cancer cells in the BM of 52 patients with locoregionally restricted primary breast cancer using immunocytochemical double labeling with monoclonal antibody 9G6 to the p185erbB2 oncoprotein. Expression of p185erbB2 on BM micrometastases was detected in 31 of 52 (60%) patients independent of established risk factors such as lymph node involvement, primary tumor size, differentiation grade, or expression of p185erbB2 on primary tumor cells. After a median follow-up of 64 months, patients with p185erbB2-positive BM micrometastases had developed fatal metastatic relapses more frequently than patients with p185erbB2-negative micrometastases (21 versus 7 events; P = 0.032). In multivariate analysis, the presence of p185erbB2-positive micrometastases was an independent prognostic factor with a hazard ratio of 2.78 (95% confidence interval, 1.11-6.96) for overall survival (P = 0.029). We therefore conclude that erbB2 overexpression characterizes a clinically relevant subset of breast cancer micrometastases.
PMID: 11280743 [PubMed - indexed for MEDLINE]
Many papers have discussed that these are cells which are not affected by chemotherapy (according to the stem cell theory of breast cancer they are dormant cells which only very rarely divide and thus are relatively "immune" from the effects of chemotherapy) Since they stain for her2neu, they should be sensitive to herceptin, however.
When I have discussed this I have gotten three answers 1) from someone whose lab does the testing--"I don't know why not" 2) from an oncologist--
we don't want to subject our patients to that test as noone likes to have their bone marrow biopsied (!!!!!!!!!this, from someone who orders hundreds of people-- many of whom would do equally well without it, as they have been unable to test to find just those who need chemotherapy--to be given chemotherapy the effect of which lasts more than a few hours or days and which can lead to long-standing problems and increased rates of second cancers????) 3) because not all labs are good at processing the marrow and doing the test equally well although the technique protocol has been well described.
I just discovered the following, a blood test, which might help indicate those patients who should have the bone marrow tested.
Glycosyltransferase Points to Breast Cancer Metastasis
By David Douglas
NEW YORK (Reuters Health) Sept 22 - The ppGalNAc-T6 molecule, one of a family of glycosyltransferases, may be a useful marker for detection of bone marrow-disseminated breast cancer cells, Uruguayan researchers report in the September 15th issue of the International Journal of Cancer.
"Our preliminary results," lead investigator Dr. Teresa Freire told Reuters Health, "suggest that the expression of this molecule would be correlated with a worse clinical outcome of patients with breast cancer."
To investigate the utility of ppGalNAc-T6 mRNA as a marker, Dr. Freire who is currently at the Institut Pasteur, Paris and colleagues conducted a variety of tests.
mRNA was found in 22 of 25 human breast cancer samples and in all 3 human cancer cell lines examined.
In addition, ppGalNAc-T6 mRNA was found in only 1 of 30 peripheral blood mononuclear cells samples obtained from patients without cancer. None was found in bone marrow samples from this group.
Furthermore, 22 of 61 breast cancer patients showed positive bone marrow aspirates before surgery. In preliminary follow-up, 11 of these patients (57.9%) experienced recurrence.
In a subgroup of patients without lymph node involvement, 54.5% of those with positive bone marrow aspirates had recurrence. This was the case in only 4.6% of those with negative findings.
"Although further studies are necessary," continued Dr. Freire, "these results also suggest that this new potential marker could be used in combination with axillary nodal status -- the only factor used consistently as a guide for therapy -- since a high rate of disease recurrence in node-negative patients showing ppGal-NAc-T6 mRNA-positive bone marrow aspirates was observed."
Int J Cancer 2006;119:1383-1388.
I know the Germans who have been instrumental in advocating bone marrow testing are starting a clinical trial to see if directing treatment by the bone marrow results will improve prognosis...
reference for the chart on the prognosis of her2+ patients with her2+ isolated tumor cells in their bone marrow:
1: Cancer Res. 2001 Mar 1;61(5):1890-5. Links
ErbB2 overexpression on occult metastatic cells in bone marrow predicts poor clinical outcome of stage I-III breast cancer patients.
Braun S,
Schlimok G,
Heumos I,
Schaller G,
Riethdorf L,
Riethmuller G,
Pantel K.
Frauenklinik & Poliklinik, Klinikum rechts der Isar, Technische Universitat, Munchen, Germany. stephan.braun@lrz.tum.de
Occult hematogenous micrometastases are the major cause for metastatic relapse and cancer-related death in patients with operable primary breast cancer. Although sensitive immunocytochemical and molecular methods allow detection of individual breast cancer cells in bone marrow (BM), a major site of metastatic relapse, current detection techniques cannot discriminate between nonviable shed tumor cells and seminal metastatic cells. To address this problem, we analyzed the relevance of erbB2 overexpression on disseminated cytokeratin-18-positive breast cancer cells in the BM of 52 patients with locoregionally restricted primary breast cancer using immunocytochemical double labeling with monoclonal antibody 9G6 to the p185erbB2 oncoprotein. Expression of p185erbB2 on BM micrometastases was detected in 31 of 52 (60%) patients independent of established risk factors such as lymph node involvement, primary tumor size, differentiation grade, or expression of p185erbB2 on primary tumor cells. After a median follow-up of 64 months, patients with p185erbB2-positive BM micrometastases had developed fatal metastatic relapses more frequently than patients with p185erbB2-negative micrometastases (21 versus 7 events; P = 0.032). In multivariate analysis, the presence of p185erbB2-positive micrometastases was an independent prognostic factor with a hazard ratio of 2.78 (95% confidence interval, 1.11-6.96) for overall survival (P = 0.029). We therefore conclude that erbB2 overexpression characterizes a clinically relevant subset of breast cancer micrometastases.
PMID: 11280743 [PubMed - indexed for MEDLINE]