TY - JOUR
T1 - Prognostic role of serum thymidine kinase 1 activity in patients with hormone receptor–positive metastatic breast cancer
T2 - Analysis of the randomised phase III Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT)
AU - McCartney, Amelia
AU - Biagioni, Chiara
AU - Schiavon, Gaia
AU - Bergqvist, Mattias
AU - Mattsson, Karin
AU - Migliaccio, Ilenia
AU - Benelli, Matteo
AU - Romagnoli, Dario
AU - Bonechi, Martina
AU - Boccalini, Giulia
AU - Pestrin, Marta
AU - Galardi, Francesca
AU - De Luca, Francesca
AU - Biganzoli, Laura
AU - Piccart, Martine
AU - Gradishar, William J.
AU - Chia, Stephen
AU - Di Leo, Angelo
AU - Malorni, Luca
N1 - Funding Information:
G.S. is an employee of AstraZeneca and holds ownership interests (including patents) in the company. M.Ber. and K.M. are employees of Biovica International and hold stock/stock options in the company. L.B. reports an advisory role and lecture fees/honoraria from Novartis, AstraZeneca and Pfizer. M.Pic. declares honoraria from Pfizer and AstraZeneca. A.D.L. declares an advisory role and lecture fees/honoraria from AstraZeneca, Novartis and Pfizer and holds research grants from Pfizer and Novartis. L.M. is a consultant for AstraZeneca, Pfizer and Novartis. A.M., C.B., I.M., M.Ben., D.R., M.Bon., G.B., M.Pes., F.G., F.D.L., W.J.G. and S.C. declare no competing conflicts of interest for the work under consideration.
Funding Information:
This work was funded in part by a research grant from Associazione Italiana per la Ricerca sul Cancro (MFAG grant number 18880 to LM).
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/6
Y1 - 2019/6
N2 - Background: Thymidine kinase 1 (TK1) plays a critical role in DNA synthesis and cell proliferation. Recent studies have shown potential for serum TK1 activity (sTKa) as a prognostic marker and indicator of early response to endocrine therapy in advanced breast cancer. The aim of this study is to assess the correlation between sTKa and patient outcome. Patients and methods: The Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) was a double-blind, double-dummy, randomised trial of fulvestrant versus exemestane after progression on non-steroidal aromatase inhibitor therapy, in postmenopausal women with advanced breast cancer. Retrospective analyses of serum archived from EFECT were conducted. sTKa was assessed using the DiviTum® assay on samples collected at baseline, after three and six months of endocrine therapy, and at disease progression. Results: The median time to progression (mTTP) for patients with low baseline sTKa levels was 5.03 months (95% confidence interval [CI]: 3.91–5.89) versus 2.57 months (95% CI: 2.04–3.52) in patients with high sTKa baseline levels (P < 0.0001). On treatment, patients whose sTKa increased from baseline had a significantly shorter mTTP (3.39 months, 95% CI: 2.14–4.11) than those without an sTKa increase (5.39 months, 95% CI: 4.01–6.68) (P = 0.0045). Similar results were observed in the separate EFECT treatment arms. After adjusting for major prognostic factors, sTKa remained an independent marker. Conclusion: sTKa is a potential circulating prognostic marker in patients with advanced breast cancer treated with endocrine therapy. It may also represent a tool for upfront identification of endocrine therapy resistance and early positive response to therapy. Independent validation of these results is warranted.
AB - Background: Thymidine kinase 1 (TK1) plays a critical role in DNA synthesis and cell proliferation. Recent studies have shown potential for serum TK1 activity (sTKa) as a prognostic marker and indicator of early response to endocrine therapy in advanced breast cancer. The aim of this study is to assess the correlation between sTKa and patient outcome. Patients and methods: The Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT) was a double-blind, double-dummy, randomised trial of fulvestrant versus exemestane after progression on non-steroidal aromatase inhibitor therapy, in postmenopausal women with advanced breast cancer. Retrospective analyses of serum archived from EFECT were conducted. sTKa was assessed using the DiviTum® assay on samples collected at baseline, after three and six months of endocrine therapy, and at disease progression. Results: The median time to progression (mTTP) for patients with low baseline sTKa levels was 5.03 months (95% confidence interval [CI]: 3.91–5.89) versus 2.57 months (95% CI: 2.04–3.52) in patients with high sTKa baseline levels (P < 0.0001). On treatment, patients whose sTKa increased from baseline had a significantly shorter mTTP (3.39 months, 95% CI: 2.14–4.11) than those without an sTKa increase (5.39 months, 95% CI: 4.01–6.68) (P = 0.0045). Similar results were observed in the separate EFECT treatment arms. After adjusting for major prognostic factors, sTKa remained an independent marker. Conclusion: sTKa is a potential circulating prognostic marker in patients with advanced breast cancer treated with endocrine therapy. It may also represent a tool for upfront identification of endocrine therapy resistance and early positive response to therapy. Independent validation of these results is warranted.
KW - Biomarker
KW - Breast cancer
KW - EFECT
KW - Endocrine resistance
KW - Prognosis
KW - Treatment response
UR - http://www.scopus.com/inward/record.url?scp=85065012950&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2019.04.002
DO - 10.1016/j.ejca.2019.04.002
M3 - Article
C2 - 31059974
AN - SCOPUS:85065012950
SN - 0959-8049
VL - 114
SP - 55
EP - 66
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -
