444 Predictive outcome assessment and monitoring by serum testing for HER-2/neu, EGFR, uPA and CA 27.29 in metastatic breast cancer

Lüftner, Diana; Henschke, P.; Geppert, R.; Carney, Walter P.; Wernecke, KD; Possinger, K.

doi:10.1016/s1359-6349(03)90476-9

“…Multivariate analysis was not reported in the abstract. In the third, smallest study serum uPA was analyzed in 111 patients with metastatic BC; uPA levels were not prognostically significant 46 . Again, the results have not been fully published since they were reported at the ECCO European Cancer Conference in 2003.…”

Section: Discussionmentioning

confidence: 99%

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

Banys-Paluchowski

¹

,

Witzel

²

,

Aktas

³

et al. 2019

Sci Rep

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In breast cancer (BC), elevated levels of urokinase-type plasminogen activator (uPA) in tumor tissue have been confirmed as a strong prognostic factor in level-of-evidence-1 studies. The aim of the present study was to evaluate the clinical relevance of uPA levels in serum of metastatic BC patients and to compare uPA with other blood-based biomarkers. 252 patients were enrolled in this prospective, multicentre study. Blood samples were collected before begin of first-line or later-line systemic treatment. Serum uPA was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch; other biomarkers (EGFR, VEGF, HER2, RAS p21, TIMP1, CAIX) by ELISA. Using the ROC analysis, the optimal cut-off value (determined by the Youden index) of serum uPA was 2.52 ng/ml. Using this value, 26% of patients had elevated uPA levels. Patients with visceral metastasis and more than one metastatic site were significantly more likely to present with elevated uPA levels. CTC status, serum HER2, RAS p21, CAIX, TIMP1 and VEGF correlated significantly with uPA levels. Elevated uPA levels predicted shorter overall and progression-free survival in univariate analysis (median OS: 7.5 months [95%-CI 4.5–10.5 months] vs. not reached, p < 0.001; PFS: 4.8 [95%-CI: 3.1–6.5] vs. 9.1 [7.4–10.8] months, p < 0.001). In multivariate analysis, elevated uPA, presence of ≥5 CTCs, elevated RAS p21, higher grading and higher line of therapy were independent predictors of shorter OS, while elevated CTC counts, higher line of therapy and negative estrogen receptor status were independent predictors of shorter PFS. In conclusion, elevated uPA levels independently predict reduced overall survival and improved prognostication in patients with known CTC status. Whether high serum uPA might identify patients most likely to benefit from therapies targeting uPA, remains to be evaluated in future trials.

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“…To date, no other trial on the prognostic relevance of serum uPA in metastatic BC has been fully published. Results from three studies are available as conference abstracts only [45][46][47] . Kang et al evaluated the prognostic and predictive effects of various serum biomarkers, among them uPA, in HER2-positive patients enrolled in the MA.31 trial (NCT00667251) treated by chemotherapy with lapatinib or trastuzumab 45 .…”

Section: Discussionmentioning

confidence: 99%

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

Banys-Paluchowski

¹

,

Fehm

²

,

Witzel

³

et al. 2018

Geburtshilfe Und Frauenheilkunde

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In breast cancer (BC), elevated levels of urokinase-type plasminogen activator (uPA) in tumor tissue have been confirmed as a strong prognostic factor in level-of-evidence-1 studies. The aim of the present study was to evaluate the clinical relevance of uPA levels in serum of metastatic BC patients and to compare uPA with other blood-based biomarkers. 252 patients were enrolled in this prospective, multicentre study. Blood samples were collected before begin of first-line or later-line systemic treatment. Serum uPA was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch; other biomarkers (EGFR, VEGF, HER2, RAS p21, TIMP1, CAIX) by ELISA. Using the ROC analysis, the optimal cut-off value (determined by the Youden index) of serum uPA was 2.52 ng/ml. Using this value, 26% of patients had elevated uPA levels. Patients with visceral metastasis and more than one metastatic site were significantly more likely to present with elevated uPA levels. CTC status, serum HER2, RAS p21, CAIX, TIMP1 and VEGF correlated significantly with uPA levels. Elevated uPA levels predicted shorter overall and progression-free survival in univariate analysis (median OS: 7.5 months [95%-CI 4.5-10.5 months] vs. not reached, p < 0.

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“…In this experiment, adjusting a laser power at low value, which can barely ionize digested peptide fragments, might not cause large decreases in the resolution or mass accuracy. These identified proteins are known to be phosphoproteins in various species including human [15,16]. In particular, moesin, ezrin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) have already been shown to be phosphorylated on specific tyrosine residues in an EGF-dependent manner in A-431 cells [17][18][19].…”

Section: On-membrane Direct Identification Of Proteins Detected With mentioning

confidence: 99%

Direct on-membrane peptide mass fingerprinting with MALDI–MS of tyrosine-phosphorylated proteins detected by immunostaining

Nakanishi

¹

,

Ando

²

,

Furuta

³

et al. 2007

Journal of Chromatography B

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444 Predictive outcome assessment and monitoring by serum testing for HER-2/neu, EGFR, uPA and CA 27.29 in metastatic breast cancer

Cited by 3 publications

References 0 publications

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer

Direct on-membrane peptide mass fingerprinting with MALDI–MS of tyrosine-phosphorylated proteins detected by immunostaining

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