Lani
05-03-2007, 11:33 AM
I have previously posted papers showing in both metastatic and early bc patients receiving neoadjuvant therapy that a decrease in serum her2ECD of ~20% between the preherceptin level and that after three weeks of treatment (drawn prior to the dose) or so seemed to indicate efficacy of herceptin treatment.
I have also posted that herceptin seems to downregulate T reg cells which keeps the immune system from recognizing the her2 breast cancer cells as "foreign" and attacking them. Here is evidence that monitoring the level of T regs, like the her2 ECD might indicate which patients herceptin is effective in.
Perhaps finding this out early and doing more tests (such as measuring PTEN, truncated her 2 levels, etc) might help figure out whether adding another medication or switching to Tykerb would be helpful in such patients
Just food for thought
1: Clin Cancer Res. 2007 May 1;13(9):2714-21.
CD4+CD25+ Regulatory T-Cell Frequency in HER-2/neu (HER)-Positive and HER-Negative Advanced-Stage Breast Cancer Patients.
Perez SA,
Karamouzis MV,
Skarlos DV,
Ardavanis A,
Sotiriadou NN,
Iliopoulou EG,
Salagianni ML,
Orphanos G,
Baxevanis CN,
Rigatos G,
Papamichail M.
Authors' Affiliations: Cancer Immunology and Immunotherapy Center and First Department of Medical Oncology, Saint Savas Cancer Hospital.
PURPOSE: CD4(+)CD25(bright) regulatory T cells (Tregs) are increased in patients with several malignancies and correlate with disease stage and prognosis. Breast cancer patients represent a heterogeneous population with unpredictable disease progression even at advanced stages. Circulating Tregs in correlation with HER-2/neu (HER) status and treatment with chemotherapy, either alone or in combination with trastuzumab therapy, were monitored in advanced-stage breast cancer patients. EXPERIMENTAL DESIGN: Circulating Treg frequency and absolute counts of 46 HER(+) and 28 HER(-), stage III and IV, breast cancer patients before therapy and during trastuzumab therapy and/or chemotherapy have been compared with 24 healthy donors and correlated with plasma HER extracellular domain concentration and clinical outcome. RESULTS: Treg frequency in HER(+) patients was significantly increased compared with both HER(-) patients and healthy donors. Trastuzumab therapy, with or without combined chemotherapy, resulted in a progressive decrease of circulating Tregs. Percentage change in Tregs statistically correlated with percentage change in plasma HER extracellular domain. Furthermore, decrease in Tregs correlated with either objective clinical response or stable disease, whereas increased Treg frequency during trastuzumab therapy coincided with disease progression. No statistically significant change in Treg frequency following chemotherapy was observed in HER(-) patients. CONCLUSIONS: Treg cell frequency does not directly correlate with clinical stage in breast cancer, as stage III and IV HER(+) and HER(-) patients exhibit significantly different Treg profiles. Trastuzumab therapy, either alone or combined with chemotherapy, results in decreased Treg frequency in HER(+) advanced patients with an objective clinical response.
PMID: 17473204 [PubMed - in process]
I have also posted that herceptin seems to downregulate T reg cells which keeps the immune system from recognizing the her2 breast cancer cells as "foreign" and attacking them. Here is evidence that monitoring the level of T regs, like the her2 ECD might indicate which patients herceptin is effective in.
Perhaps finding this out early and doing more tests (such as measuring PTEN, truncated her 2 levels, etc) might help figure out whether adding another medication or switching to Tykerb would be helpful in such patients
Just food for thought
1: Clin Cancer Res. 2007 May 1;13(9):2714-21.
CD4+CD25+ Regulatory T-Cell Frequency in HER-2/neu (HER)-Positive and HER-Negative Advanced-Stage Breast Cancer Patients.
Perez SA,
Karamouzis MV,
Skarlos DV,
Ardavanis A,
Sotiriadou NN,
Iliopoulou EG,
Salagianni ML,
Orphanos G,
Baxevanis CN,
Rigatos G,
Papamichail M.
Authors' Affiliations: Cancer Immunology and Immunotherapy Center and First Department of Medical Oncology, Saint Savas Cancer Hospital.
PURPOSE: CD4(+)CD25(bright) regulatory T cells (Tregs) are increased in patients with several malignancies and correlate with disease stage and prognosis. Breast cancer patients represent a heterogeneous population with unpredictable disease progression even at advanced stages. Circulating Tregs in correlation with HER-2/neu (HER) status and treatment with chemotherapy, either alone or in combination with trastuzumab therapy, were monitored in advanced-stage breast cancer patients. EXPERIMENTAL DESIGN: Circulating Treg frequency and absolute counts of 46 HER(+) and 28 HER(-), stage III and IV, breast cancer patients before therapy and during trastuzumab therapy and/or chemotherapy have been compared with 24 healthy donors and correlated with plasma HER extracellular domain concentration and clinical outcome. RESULTS: Treg frequency in HER(+) patients was significantly increased compared with both HER(-) patients and healthy donors. Trastuzumab therapy, with or without combined chemotherapy, resulted in a progressive decrease of circulating Tregs. Percentage change in Tregs statistically correlated with percentage change in plasma HER extracellular domain. Furthermore, decrease in Tregs correlated with either objective clinical response or stable disease, whereas increased Treg frequency during trastuzumab therapy coincided with disease progression. No statistically significant change in Treg frequency following chemotherapy was observed in HER(-) patients. CONCLUSIONS: Treg cell frequency does not directly correlate with clinical stage in breast cancer, as stage III and IV HER(+) and HER(-) patients exhibit significantly different Treg profiles. Trastuzumab therapy, either alone or combined with chemotherapy, results in decreased Treg frequency in HER(+) advanced patients with an objective clinical response.
PMID: 17473204 [PubMed - in process]