bPrognostic role of serum thymidine kinase 1 kinetics during neoadjuvant chemotherapy for early breast cancer

被引：7

作者：

Matikas, A. ^{[1
,2
]}

Wang, K. ^{[1
]}

Lagoudaki, E. ^{[3
]}

Acs, B. ^{[1
,4
]}

Zerdes, I ^{[1
]}

Hartman, J. ^{[1
,4
]}

Azavedo, E. ^{[5
]}

Bjohle, J. ^{[2
]}

Carlsson, L. ^{[6
]}

Einbeigi, Z. ^{[7
,8
,9
]}

Hedenfalk, I ^{[10
]}

Hellstrom, M. ^{[1
]}

Lekberg, T. ^{[1
,2
]}

Loman, N. ^{[10
,11
]}

Saracco, A. ^{[12
]}

von Wachenfeldt, A. ^{[13
]}

Rotstein, S. ^{[2
]}

Bergqvist, M. ^{[14
]}

Bergh, J. ^{[1
,2
]}

Hatschek, T. ^{[1
,2
]}

Foukakis, T. ^{[1
,2
]}

机构：

[1] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden

[2] Karolinska Univ Hosp, Breast Ctr, Theme Canc, Gavlegatan 55, S-17164 Stockholm, Sweden

[3] Univ Hosp Heraklion, Pathol Dept, Iraklion, Greece

[4] Karolinska Univ Lab, Dept Clin Pathol & Cytol, Stockholm, Sweden

[5] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[6] Sundsvall Gen Hosp, Dept Oncol, Sundsvall, Sweden

[7] Southern Alvsborg Hosp, Dept Med, Boras, Sweden

[8] Southern Alvsborg Hosp, Dept Oncol, Boras, Sweden

[9] Sahlgrens Acad, Sahlgrenska Univ Hosp, Inst Clin Sci, Gothenburg, Sweden

[10] Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden

[11] Skane Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund, Sweden

[12] Soder Sjukhuset, Breast Ctr, Stockholm, Sweden

[13] Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden

[14] Biov Int, Uppsala Sci Pk, Uppsala, Sweden

来源：

ESMO OPEN | 2021年 / 6卷 / 02期

基金：

瑞典研究理事会;

关键词：

breast cancer; longitudinal; neoadjuvant chemotherapy; prognosis; thymidine kinase 1; TK1; kinetics; DIGITAL-IMAGE-ANALYSIS; INTERNATIONAL KI67; RECOMMENDATIONS; THERAPY; MARKER; PROLIFERATION; CAPECITABINE; EXPRESSION; DOCETAXEL; BIOMARKER;

D O I：

10.1016/j.esmoop.2021.100076

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Emerging data support the use of thymidine kinase 1 (TK1) activity as a prognostic marker and for monitoring of response in breast cancer (BC). The long-term prognostic value of TK1 kinetics during neoadjuvant chemotherapy is unclear, which this study aimed to elucidate. Methods: Material from patients enrolled to the single-arm prospective PROMIX trial of neoadjuvant epirubicin, docetaxel and bevacizumab for early BC was used. Ki67 in baseline biopsies was assessed both centrally and by automated digital imaging analysis. TK1 activity was measured from blood samples obtained at baseline and following two cycles of chemotherapy. The associations of TK1 and its kinetics as well as Ki67 with event-free survival and overall survival (OS) were evaluated using multivariable Cox regression models. Results: Central Ki67 counting had excellent correlation with the results of digital image analysis (r = 0.814), but not with the diagnostic samples (r = 0.234), while it was independently prognostic for worse OS [adjusted hazard ratio (HRadj) = 2.72, 95% confidence interval (CI) 1.19-6.21, P = 0.02]. Greater increase in TK1 activity after two cycles of chemotherapy resulted in improved event-free survival (HRadj = 0.50, 95% CI 0.26-0.97, P = 0.04) and OS (HRadj = 0.46, 95% CI 0.95, P = 0.04). There was significant interaction between the prognostic value of TK1 kinetics and Ki67 (p(interaction) 0.04). Conclusion: Serial measurement of serum TK1 activity during neoadjuvant chemotherapy provides long-term prognostic information in BC patients. The ease of obtaining serial samples for TK1 assessment motivates further evaluation in larger studies.

引用

页数：9

共 51 条

[21] Elevated thymidine kinase 1 in serum following neoadjuvant chemotherapy predicts poor outcome for patients with locally advanced breast cancer [J].