Can thymidine kinase levels in breast tumors predict disease recurrence?

Abstract

Background: Our previous study of thymidine kinase (TK) levels in the serum of breast cancer patients demonstrated a statistically significant positive correlation with cancer stage. In postsurgical follow-up studies of 20 patients with primary breast cancer, total serum TK levels rose with disease recurrence and continued to rise with disease progression but decreased with treatment response.

Purpose: This study was designed to examine whether TK levels in primary breast tumors can be used to predict recurrence and to establish the relationship between TK levels and estrogen receptor (ER) status and recurrence.

Methods: Eighty-six patients with breast cancer were entered in this study. Tumors were assessed for ER status and TK levels, and the patients had follow-up for recurrence over a period of 41 months. By calculating the percent of TK activity in the presence of adenosine triphosphate (ATP) or cytidine triphosphate (CTP), we estimated the relative contributions of TK isozymes TK1 and TK2 to total TK activity.

Results: Total TK (TK1 plus TK2) levels in tumors were significantly (P < .001) elevated in patients who subsequently had recurrence compared with levels in those who did not. Calculations of the percent of TK activity in the presence of ATP or CTP showed that this elevation was due to increased TK1 isozyme levels. ER-negative (ER-) patients had significantly (P < .001) increased TK1 levels relative to those in ER-positive (ER+) patients. ER- patients with recurrence had significantly (P < .001) elevated total tumor TK levels compared with levels in those who did not have recurrence, and calculation of percent of TK activity with ATP or CTP indicated elevated TK1 levels. A similar pattern of increased levels of total tumor TK and TK1 was observed in ER+ patients with recurrence.

Conclusions: The results indicate that total tumor TK levels were significantly higher in breast cancer patients who subsequently had recurrence than levels in those who did not. This finding appears to be largely caused by higher levels of TK1.

Implications: Higher TK1 levels in tumors in patients who subsequently had disease recurrence almost certainly indicate a high rate of proliferation in such tumors at the time of excision. It appears that TK is a potentially useful marker in the management of breast cancer. With measurement of levels of TK, particularly TK1, in breast tumors and serum, it may be possible to predict recurrence of breast cancer.