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 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.

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 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.

First line trastuzumab-based therapy in HER2-positive metastatic breast cancer patients (MBC) presenting with de novo or recurrent disease.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e11575-e11575
Author(s):  
Francesca Poggio ◽  
Matteo Lambertini ◽  
Arlindo Rebelo Ferreira ◽  
Fabio Puglisi ◽  
Antonio Bernardo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
De Novo ◽  
Recurrent Disease ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
First Line ◽  
Her2 Positive

Circulating PD-L1 (programmed death-ligand 1) and outcomes in a HER2-positive metastatic breast cancer cohort treated with first-line trastuzumab.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1024-1024 ◽  
Author(s):  
Ayesha Ali ◽  
Laura Krecko ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Joseph J. Drabick ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
First Line ◽  
Her2 Positive ◽  
Breast Cancer Cohort

1024 Background: Recently the immune checkpoint inhibitors (ICIs) have demonstrated efficacy across a wide variety of cancers, but have been less effective in breast cancer. PD-L1 (B7-H1, CD274) is a ligand produced by many tumor cells and some immune cells, and suppresses the T cell immune response. This allows tumor cells to escape immune detection. PD-L1 is used as a companion tumor tissue IHC biomarker for patient selection for some of the FDA-approved ICIs (pembrolizumab), but not for others (nivolumab, atezolizumab). Circulating PD-L1 has been detected in multiple myeloma, renal, lung, and gastric cancer, but not in breast cancer. Here we correlated serum PD-L1 levels with outcome in a HER2-positive metastatic breast cancer cohort treated with trastuzumab. Methods: Pretreatment serum was obtained from 63 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. A novel ELLA microfluidic channel immunoassay platform (ProteinSimple, San Jose, CA) was employed to quantitate serum PD-L1. Serum PD-L1 levels were analyzed using continuous, quartile, and dichotomous (25%, median, and 75%) cutpoints. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Results: On a continuous basis, patients with higher serum PD-L1 had a significantly reduced PFS (p = 0.045) and overall survival OS (p = 0.004) compared to patients with lower serum PD-L1 levels. Patients with the higher quartiles of serum PD-L1 also trended to have reduced PFS (0.11) and significantly reduced OS (p = 0.015) compared to the lower quartiles of serum PD-L1. Finally, using either the 25th or 75th percentile of serum PD-L1 as dichotomous cutpoint, patients with higher serum PD-L1 had significantly reduced OS (p = 0.04). Conclusions: Higher circulating PD-L1 levels were prognostic for reduced PFS and OS in HER2-positive metastatic breast cancer patients treated with first-line trastuzumab. Circulating PD-L1 deserves further study for prognostic and predictive biomarker utility in larger trials of immune checkpoint inhibitors and other immunotherapies in breast and other cancers. AA, LK contributed equally.

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