This systematic review and meta-analysis evaluated the prognostic value of circulating thymidine kinase 1 activity (TKa) — measured at baseline and on-treatment (weeks 2 and 4) — in women with hormone receptor-positive (HR+) metastatic breast cancer (MBC), pooling hazard ratios for PFS and OS from 18 studies (~3,000 patients).
High baseline TKa was associated with significantly worse PFS (HR 1.90; 95% CI 1.57–2.30) and OS (HR 2.48; 95% CI 1.94–3.17). On-treatment TKa also remained prognostic: at 2 weeks (PFS HR 2.76; 95% CI 2.34–3.26) and at 4 weeks (PFS HR 2.26; 95% CI 1.93–2.66), all p < 0.001.
- Results were heterogeneous across included studies (I² reported; prediction intervals used, but residual heterogeneity likely from variable TKa cut-offs and assay types). - Only 15 of 18 studies could be meta-analyzed, limiting completeness. - Evidence is restricted to women; generalizability to other sexes or HR-negative subtypes is unknown.
Consider measuring circulating TKa before and early during treatment in HR+ MBC — high TKa at baseline or within the first 4 weeks signals a substantially higher risk of progression and death, and may serve as an early indicator of treatment resistance. Standardization of cut-offs and assay methods is still needed before routine clinical adoption.
Explore related topics
