Elevated pretreatment serum activin A and progression-free and overall survival in trastuzumab-treated metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 607-607
Author(s):  
Allan Lipton ◽  
Lindsey Zubritsky ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Wolfgang Koestler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Activin A ◽  
Breast Cancer Patients ◽  
First Line ◽  
Pretreatment Serum

607 Background: About half of HER2-positive metastatic breast cancer patients will respond tofirst-line trastuzumab-containing therapy, but most will progress within a year. Trastuzumab resistance remains a vexing clinical problem, and better predictive and prognostic biomarkers are needed. Activin A is a TGF-B superfamily member and regulates cell proliferation, apoptosis, differentiation, and immune response. Methods: Serum activin A was measured using ELISA (R&D Systems, Minneapolis, MN) in 60 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) serum activin A analyses. Results: Pretreatment serum activin A levels averaged 2376 pg/ml, and had a median of 629 pg/ml and 25th and 75th quartile values of 406 and 1791 pg/ml, respectively. Patients who were hormone receptor negative had significantly higher activin A levels (median 1287 vs 450 pg/ml, p=0.002). Higher serum activin A was significant on a continuous basis for predicting reduced PFS to first-line trastuzumab-containing therapy (p<0.003), and for predicting shorter OS (p<0.0001). When analyzed using a dichotomous (median) cutpoint, the elevated serum activin A cohort had a significantly reduced PFS (HR 2.79, p <0. 002) (median 6.6 mo vs. 31.1 mo) and OS (HR 5.24, p <0.0001) (median 19.6 mo vs. median not reached). In multivariate analysis for PFS with other covariates (age, line of therapy, CA 15-3, and hormone receptor status), activin A was the only significant covariate (p=0.021). In multivariate analysis for OS, activin A (p=0.002) and CA 15-3 (p=0.03) remained significant as prognostic factors. Conclusions: Elevated pretreatment serum activin A predicts reduced PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Activin A deserves further study as an adverse biomarker, and to select patients most likely to respond to activin A-targeted therapy.

Elevated pretreatment serum activin A and progression-free and overall survival in trastuzumab-treated metastatic breast cancer.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 38-38
Author(s):  
Lindsey Zubritsky ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Wolfgang Köstler ◽  
Eva-Maria Fuchs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Activin A ◽  
Breast Cancer Patients ◽  
First Line ◽  
Pretreatment Serum

38 Background: About half of HER2-positive metastatic breast cancer patients will respond tofirst-line trastuzumab-containing therapy, but most will progress within a year. Trastuzumab resistance remains a vexing clinical problem, and better predictive and prognostic biomarkers are needed. Activin A is a TGF-B superfamily member and regulates cell proliferation, apoptosis, differentiation, and immune response. Methods: Serum activin A was measured using ELISA (R&D Systems, Minneapolis, MN) in 60 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) serum activin A analyses. Results: Pretreatment serum activin A levels averaged 2376 pg/ml, and had a median of 629 pg/ml and 25th and 75th quartile values of 406 and 1791 pg/ml, respectively. Patients who were hormone receptor negative had significantly higher activin A levels (median 1287 vs 450 pg/ml, p=0.002). Higher serum activin A was significant on a continuous basis for predicting reduced PFS to first-line trastuzumab-containing therapy (p<0.003), and for predicting shorter OS (p<0.0001). When analyzed using a dichotomous (median) cutpoint, the elevated serum activin A cohort had a significantly reduced PFS (HR 2.79, p <0. 002) (median 6.6 mo vs. 31.1 mo) and OS (HR 5.24, p <0.0001) (median 19.6 mo vs. median not reached). In multivariate analysis for PFS with other covariates (age, line of therapy, CA 15-3, and hormone receptor status), activin A was the only significant covariate (p=0.021). In multivariate analysis for OS, activin A (p=0.002) and CA 15-3 (p=0.03) remained significant as prognostic factors. Conclusions: Elevated pretreatment serum activin A predicts reduced PFS and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. Activin A deserves further study as an adverse biomarker, and to select patients most likely to respond to activin A-targeted therapy.

Use of pretreatment serum CA9 (carbonic anhydrase 9) to predict PFS and survival in trastuzumab-treated metastatic breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11092-11092
Author(s):  
K. Leitzel ◽  
H. Y. Hou ◽  
V. Shrivastava ◽  
U. Anyanwu ◽  
S. M. Ali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
First Line ◽  
Her2 Positive ◽  
Pretreatment Serum

11092 Background: Approximately half of HER2-positive breast cancer patients will respond to first-line trastuzumab-containing therapy. However, in those patients with an initial trastuzumab response, most will progress within a year with acquired resistance. Since trastuzumab treatment is also now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a vexing clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Serum HER2, tissue inhibitor of metalloproteinase-1 (TIMP-1), urokinase-type plasminogen activator (uPA), CA9, VEGF-165, and endoglin were measured using ELISA assays in 66 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. The HER2, TIMP-1, uPA, CA9, and VEGF-165 ELISAs were from Oncogene Science/Siemens Healthcare Diagnostics, Cambridge, MA; and the endoglin ELISA was from R&D Systems, Minneapolis, MN. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with continuous pretreatment serum biomarker variables. Results: Pretreatment serum HER2 (p= 0.005), TIMP-1 (p< 0.0001), uPA (p= 0.006), endoglin (p= 0.008), and CA9 (p <0.0001) were all significant as univariate continuous biomarkers for predicting PFS to first-line trastuzumab-containing therapy, but VEGF was not. In multivariate analysis for PFS with all six biomarkers, only serum CA9 (p= 0.002) was a significant independent covariate. For OS, pretreatment serum HER2 (p= 0.018), TIMP-1 (p< 0.0001), uPA (p< 0.0001), endoglin (p= 0.002), and CA9 (p< 0.0001) were all significant as univariate continuous biomarkers for prognosis, but serum VEGF was not. In multivariate analysis for OS with all six biomarkers, only serum CA9 was a significant independent prognostic covariate (p= 0.001). Conclusions: Elevated pretreatment serum CA9 (a marker of hypoxia) predicts reduced progression-free survival and overall survival in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure. [Table: see text]

Elevated pretreatment serum biomarkers and correlation with progression-free (PFS) and overall survival (OS) in first-line trastuzumab-treated metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 622-622
Author(s):  
Suhail M. Ali ◽  
Kim Leitzel ◽  
Uchechi Anyanwu ◽  
Hui Ying Hou ◽  
Matthew Stephen Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Serum Biomarkers ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Breast Cancer Patients ◽  
First Line ◽  
Her2 Positive ◽  
Pretreatment Serum

622 Background: Approximately one-half of HER2-positive breast cancer patients will respond tofirst-line trastuzumab-containing therapy. However, in those patients with an initial trastuzumab response, most will progress within a year with acquired resistance. Since trastuzumab treatment is also now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a recurring clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Seven serum biomarkers (carbonic anhydrase 9 (CA9), endoglin, HER2, IGF-1R, tissue inhibitor of metalloproteinase-1 (TIMP-1), urokinase-type plasminogen activator (uPA), and VEGF-A (isoform 165) were measured using ELISA assays in 81 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. The endoglin and IGF-IR ELISAs were from R&D Systems; others were from WILEX/Oncogene Science, Cambridge, MA. PFS and OS were analyzed using the Kaplan-Meier method and Cox modeling with continuous pretreatment serum biomarker variables. Results: For univariate PFS analysis, higher pretreatment serum biomarkers (except IGF-1R and VEGF-A) predicted reduced PFS (p<0.05) to first-line trastuzumab-containing therapy. In multivariate PFS analysis, only serum CA9 (p= 0.038) remained a significant independent covariate. In univariate OS analysis, higher pretreatment serum biomarkers (except IGF-1R and VEGF-A) were prognostic for reduced OS (p<0.05). In multivariate analysis for OS, TIMP-1 (p=0.001) and CA9 (p=0.04) remained significant independent prognostic factors, as well as line of chemotherapy (3 vs. 2 or 1 line)(p=0.005), and hormone receptor status (ER and/or PR positive vs. negative)(p=0.013). Conclusions: Higher pretreatment serum CA9 (a marker of hypoxia) predicted reduced PFS, and higher serum CA9 and TIMP-1 predicted reduced OS in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure.

Lymphopenia combined with low TCR diversity to predict overall survival in metastatic breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10562-10562
Author(s):  
Manuarii Manuel ◽  
Olivier Tredan ◽  
Thomas Bachelot ◽  
Gilles Clapisson ◽  
Anais Courtier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Metastatic Breast Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Lymphocyte Count ◽  
Metastatic Breast ◽  
First Line ◽  
Tcr Diversity

10562 Background: Lymphopenia (<1 Giga/L) before initiation of chemotherapy is a predictive factor for toxicity and death in metastatic phase for cancer patients. Combinatorial diversity of T Cell Receptor beta chain (TCR-ß), as a measure of T cell repertoire diversity, was investigated and tested either alone or in combination with lymphopenia as a prognostic factor for overall survival (OS) in first line treatment of metastatic breast cancer (MBC) patients. Methods: Using semi quantitative multiplex PCR, the V-D-J combinatorial diversity of the TCR was measured on cryo-preserved blood samples from 2 cohorts of MBC patients before the initiation of the first line chemotherapy: in an experimental cohort (cohort A, n=66) and in a validation series (cohort B, n=67). A prognostic score, defined NDL (Number & Diversity of Lymphocytes) combining lymphocyte count and TCR diversity was delineated. Univariate and multivariate analysis of prognostic factors for OS were performed in both cohorts. Results: Lymphopenia (<1 Giga/L) was associated with shorter OS for cohort B while TCR diversity ≤33% (called divpenia) was associated with a reduced OS in cohort A. The combination of lymphopenia with low TCR diversity (called lympho-divpenia) was associated with poor OS compared to patients with either lymphocyte count ≥1 Giga/L or diversity >33% or both, in cohort A (median OS: 7.6 vs 24.5 months, p.value =0.0006) and cohort B (median OS 10.6 vs 22.9 months, p.value =0.0035). In a multivariate analysis, including all significant clinical factors from the univariate analysis (PS, liver metastasis, hemoglobin) lympho-divpenia was found to be an independent prognostic factor in the pooled cohort (A+B) (p=0.005) along with triple negative tumors (p=0.011) and hemoglobin level (11.5 g/dL) (p=0.009). Conclusions: NDL score combining lymphopenia and reduced TCR diversity seems to be a strong prognostic factor for OS and could be use to improve care quality of MBC patients.

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