Plasma thymidine kinase-1 activity predicts outcome in patients with hormone receptor positive and HER2 negative metastatic breast cancer treated with endocrine therapy

Bonechi, Martina; Galardi, Francesca; Biagioni, Chiara; Luca, Francesca De; Bergqvist, Mattias; Neumüller, Magnus; Guarducci, Cristina; Boccalini, Giulia; Gabellini, Stefano; Migliaccio, Ilenia; Leo, Angelo Di; Pestrin, Marta; Malorni, Luca

doi:10.18632/oncotarget.24700

Cited by 36 publications

(36 citation statements)

References 31 publications

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“…When evaluating changes at longer follow-up we found that decreasing sTK1 levels from 3-6 months correlated significantly to improved survival (PFS and OS). This is in line with previous studies reporting that decreasing TK1 activity levels are predictive of prognosis in patients with MBC 14,16,17 . Bonechi et al reported an improved PFS in patients with HR+/HER2-MBC showing decreasing TK1 activity levels during ET 14 .…”

Section: Discussionsupporting

confidence: 93%

“…This is in line with previous studies reporting that decreasing TK1 activity levels are predictive of prognosis in patients with MBC 14,16,17 . Bonechi et al reported an improved PFS in patients with HR+/HER2-MBC showing decreasing TK1 activity levels during ET 14 . That study only included 31 patients where 10 patients had received previous treatment for MBC and hence cannot be directly compared to our present study.…”

Section: Discussionsupporting

confidence: 93%

“…Hence, also in ChT treated patients sTK1 levels might be useful for disease monitoring at longer follow-up time points. Compared to other previously published studies evaluating sTK1 in MBC 14,16,17 , our study only included patients previously untreated for MBC. The median sTK1 level at BL was higher in this cohort, suggesting that sTK1 levels are higher in untreated patients, which is also consistent with the results that median sTK1 levels evaluated in the whole population decreased during treatment.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Self Cite

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show abstract

“…The study concluded that the analysis of TK1 activity level along with CTC count may be used as a potential prognostic, predictive, and monitoring marker to endocrine therapy for these tumor types. 178 180 These studies showed the potential of liquid biopsy components as a tool for predicting recurrence and prognosis. More validation studies are needed to confirm the clinical applications of these non-invasive liquid biopsy methods in predicting prognosis among breast cancer patients.…”

Section: Predicting Recurrence and Prognosis In Breast Cancermentioning

confidence: 98%

“…Using a refined enzyme‐linked immunosorbent assay, the researchers observed high baseline TK1 activity level and high CTC count in metastatic cases who had worse progression‐free survival rates, as well as lower response to endocrine therapy. The study concluded that the analysis of TK1 activity level along with CTC count may be used as a potential prognostic, predictive, and monitoring marker to endocrine therapy for these tumor types . Recently, in 2018, a study by Mastoraki et al investigated ESR1 epigenetic silencing and its impact on response to endocrine therapy.…”

Section: Utilization Of Liquid Biopsy For Breast Cancer In the Clinicmentioning

confidence: 99%

Liquid biopsy in breast cancer: A comprehensive review

2019

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Breast cancer is the most common cancer among women worldwide. Due to its complexity in nature, effective breast cancer treatment can encounter many challenges. Traditional methods of cancer detection such as tissue biopsy are not comprehensive enough to capture the entire genomic landscape of breast tumors. However, with the introduction of novel techniques, the application of liquid biopsy has been enhanced, enabling the improvement of various aspects of breast cancer management including early diagnosis and screening, prediction of prognosis, early detection of relapse, serial sampling and efficient longitudinal monitoring of disease progress and response to treatment. Various components of tumor cells released into the blood circulation can be analyzed in liquid biopsy sampling, some of which include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), cell‐free RNA, tumor‐educated platelets and exosomes. These components can be utilized for different purposes. As an example, ctDNA can be sequenced for genetic profiling of the tumors to enhance individualized treatment and longitudinal screening. CTC plasma count analysis or ctDNA detection after curative tumor resection surgery could facilitate early detection of minimal residual disease, aiding in the initiation of adjuvant therapy to prevent recurrence. Furthermore, CTC plasma count can be assessed to determine the stage and prognosis of breast cancer. In this review, we discuss the advantages and limitations of the various components of liquid biopsy used in breast cancer diagnosis and will expand on aspects that require further focus in future research.

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Primary Endocrine Therapy

Morgan

Wyld

2019

Management of Breast Cancer in Older Women

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Plasma thymidine kinase-1 activity predicts outcome in patients with hormone receptor positive and HER2 negative metastatic breast cancer treated with endocrine therapy

Cited by 36 publications

References 31 publications

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

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

Liquid biopsy in breast cancer: A comprehensive review

Primary Endocrine Therapy

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