Thymidine kinase as a proliferative marker: Clinical relevance in 1,692 primary breast cancer patients

Purpose: To assess the prognostic value of thymidine kinase (TK), an enzyme involved in the DNA synthesis salvage pathway, relative to other prognosti c factors in primary breast cancer. Patients and Methods: This retrospective study involved 1,692 patients with operable breast cancer heated in six Institutions (median follow-up, 82 mo nths), among the 857 node-negative patients, 135 received adjuvant chemothe rapy (fluorouracil, doxorubicin, cyclophosphamide [FAC] or fluorouracil, et oposide, and cisplatin [FEC]), TK war arrayed in cytosal with a quantitativ e radioenzymatic technique, Disease/specific survival (DSS), local recurren ce-free interval (LRI), and distant-relapse-free interval (DRI) were invest igated, Results: High TK levels were associated with large tumor rite, high histolo gic grade, and steroid hormone receptor negativity, Univariate analysis of the entire data set showed that high TK levels were related ta shorter DSS (P < 10(-5)), LRI (P < 10(-3)), and DRI (P < 10(-5)), In time-dependent Cox madels, high TK levels remained an independent predictor of the three outc omes, both In the overall population and in node-negative patients, althoug h ih prognostic value decreased over time. In node-negative patients, the i ntroduction of an interaction term in multivariate analysis suggested that chemotherapy war more efficacious for patients who hold tumors with high TK contents, In node-positive patients, high TK levels were related only to a n increased rick of LRI. Conclusion: High TK values am an important rick factor in node-negative pat ients and seem rp be associated with a beneficial effect of adjuvant FAC or FEC in patients who received adjuvant chemotherapy, The rationale of chemo therapy for patients with slowly proliferating tumors has to be discussed f rom a risk-benefit point of view.