Abstract P3-08-13: Serum thymidine kinase activity is an independent prognostic factor for progression-free and overall survival in women with metastatic breast cancer

Larsson, A.; Jansson, Sara; Bendahl, P-O; Baker, Sharyn D.; Bergqvist, Mattias; Aaltonen, Kirsimari; Rydén, Lisa

doi:10.1158/1538-7445.sabcs17-p3-08-13

Cited by 2 publications

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“…e PFS according to pTKa level changes between baseline and 4 weeks. f OS according to pTKa level changes between baseline and 4 weeks 3, and 6 months in women with MBC receiving first-line systemic therapy [23]. In ER+ HER2− MBC treated with ET only, sTKa was shown to be a prognostic factor at baseline and during treatment in the EFECT trial [13], in which the median time to progression for patients (N = 111) with low baseline serum TKa levels (< 97 Du/L) was 5.03 months (95% confidence interval [CI] 3.9-5.9) versus 2.57 months (95%CI 2.0-3.5) in patients with high baseline serum TKa levels (p < 0.0001).…”

Section: Discussionmentioning

confidence: 99%

Plasma thymidine kinase 1 activity and outcome of ER+ HER2− metastatic breast cancer patients treated with palbociclib and endocrine therapy

et al. 2020

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Purpose Previous cohort studies have reported plasma TK1 activity (pTKa) as a potential prognostic biomarker in estrogen receptor-positive (ER+) HER2-negative (HER2−) metastatic breast cancer (MBC). In this prospective study, we report here the prognostic impact of pTKa in ER+/HER2− MBC patients treated with endocrine therapy and CDK4/6 inhibitor. Experimental design Patients were included into the prospective, ethics committee-approved ALCINA study (NCT02866149). Eligibility criteria were patients with ER+/HER2− MBC treated at Institut Curie with endocrine therapy and palbociclib. Plasma samples were obtained at baseline and after 4 weeks of treatment. pTKa was quantified by the DiviTum® assay (Biovica, Sweden). Results From May 2016 to August 2018, 103 patients treated with endocrine therapy and palbociclib were included. Patients had received a median of two prior systemic therapies for MBC (range 0–14). Median follow-up was 13.8 months (range 6–31), with median PFS and OS of 9.6 months (95%CI [7.0–11.3]) and 28 months (95%CI [23–not reached]), respectively. Median baseline pTKa was 292 Du/L (range 20–27,312 Du/L, IQR [89–853]). After adjusting for other prognostic factors, baseline pTKa remained an independent prognostic factor for both PFS (HR = 1.3 95%CI [1.1–1.4], p = 0.0005) and OS (HR = 1.3 95%CI [1.2–1.6], p < 0.0001), and 4-week pTKa was associated with OS (HR = 1.6 95%CI [1.3–2], p < 0.0001). That survival prediction was significantly improved by the addition of baseline pTKa to clinicopathological characteristics. Adding pTKa changes at 4 weeks to baseline pTKa did not further increase survival prediction. Conclusion This study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/HER2− MBC patients treated with endocrine therapy and palbociclib.

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Section: Discussionmentioning

confidence: 99%

Plasma thymidine kinase 1 activity and outcome of ER+ HER2− metastatic breast cancer patients treated with palbociclib and endocrine therapy

et al. 2020

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“…Circulating tumor cells (CTCs) were enumerated using the CellSearch ™ system, described in detail previously 26 . Preliminary results have been reported at a poster session at SABCS (San Antonio Breast Cancer Symposium) 2017 27 .…”

Section: Methodsmentioning

confidence: 99%

Serial evaluation of serum thymidine kinase activity is prognostic in women with newly diagnosed metastatic breast cancer

Larsson

Bendahl

Aaltonen

et al. 2020

Sci Rep

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The rapid development of new therapies in metastatic breast cancer (MBC), entails a need for improved prognostic and monitoring tools. Thymidine kinase 1 (TK1) is involved in DNA synthesis and its activity correlates to outcome in cancer patients. The aim of this study was to evaluate serum TK1 activity (sTK1) levels in MBC patients as a tool for prognostication and treatment monitoring. 142 women with MBC scheduled for 1 st line systemic treatment were included in a prospective observational study. sTK1 was measured at baseline (BL) and at 1, 3 and 6 months and correlations to progression-free and overall survival (PFS, OS) evaluated. High sTK1 levels (above median) correlated to worse PFS and OS at BL, also after adjusting for other prognostic factors. sTK1 levels were significantly associated with PFS and OS measured from follow-up time points during therapy. Changes from 3 to 6 months during therapy significantly correlated to PFS and OS, whereas early changes did not. We could demonstrate sTK1 level as an independent prognostic factor in patients with newly diagnosed MBC. Changes in sTK1 levels from 3 to 6 months correlated to PFS and OS. Future studies of sTK1 are warranted to further define its clinical utility. Breast cancer is the most common malignant disease in women and although the 5-year survival is approaching 90%, 20-30% of women with initially local disease will develop metastatic disease 1. Even though treatment regimens have improved, the median survival in women with metastatic breast cancer (MBC) is approximately 2 years and the 5-year survival is only 25% 2. MBC is generally an incurable disease and therapy is focused on symptom palliation, extending survival and improving quality of life 2. Monitoring treatment response in MBC remains a clinical challenge and current guidelines suggest a combination of imaging, clinical assessment and in addition application of serum tumor markers if initially elevated 2-4. Imaging is golden standard for tumor response evaluations in patients with measurable disease 5. However, studies report that 10-40% of MBC patients have non-measurable disease 6,7. There is a clinical need for better tools to improve prognostication and therapy monitoring in MBC. Blood-borne markers are gaining attention since they carry real-time information on tumor progression and are easily evaluated in a simple blood test. Thymidine Kinase 1 (TK1) has been proposed as a marker of cell proliferation. The main function of TK1 is involvement in nucleotide metabolism with a fundamental role in DNA synthesis, essential for cell proliferation 8-10. In patients with different tumor types, TK1 activity has been shown to carry prognostic information and potential in tumor monitoring 11-14. In breast cancer, high TK1 activity in blood has been associated with worse prognosis 15. Serum TK1 activity (sTK1) level has been proposed as a prognostic marker in MBC patients during endocrine therapy (ET) and as an indicator for early response in these patients 16,17. Furthermore, it has been suggeste...

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Abstract P3-08-13: Serum thymidine kinase activity is an independent prognostic factor for progression-free and overall survival in women with metastatic breast cancer

Cited by 2 publications

References 0 publications

Plasma thymidine kinase 1 activity and outcome of ER+ HER2− metastatic breast cancer patients treated with palbociclib and endocrine therapy

Plasma thymidine kinase 1 activity and outcome of ER+ HER2− metastatic breast cancer patients treated with palbociclib and endocrine therapy

Serial evaluation of serum thymidine kinase activity is prognostic in women with newly diagnosed metastatic breast cancer

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