Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early-stage breast cancer receiving neoadjuvant palbociclib

Table 2 Thymidine kinase 1 activity, Ki-67 and thymidine kinase messenger RNA over time

Time point	Serum TK1		Tumor Ki-67		Tumor TK1 mRNA
Time point	Median (IQR) (Du/L) (number of cases < 20 Du/L)	No. of participants	Median (IQR) (%)	No. of participants	Median (IQR) (%)	No. of participants
Baseline (C0D1)	46 (25–73) (9 cases < 20 Du/L)	48	24.34% (12.91–34.87%)	45	0.315 (−0.178 to 1.128%)	16
Cycle 1, day 1 (C1D1)	42.55 (29–94.6) (8 cases < 20 Du/L)	49	5.37% (2.52–13.51%)^a	45	−0.42 (−1.19 to 0.47%)^b	33
Cycle 1, day 15 (C1D15)	<20 (<20 to < 20)^a (44 cases < 20 Du/L)	48	0.78% (0.24–1%)^a	45	0.98 (−1.89 to 0%)^b	29
Surgery without C5	143.96 (90.9–306.4)^a (3 cases < 20 Du/L)	31	10.63% (4.59–23.67%)^a	27	0.07 (−0.81 to 0.69%)	17
Surgery with C5	<20 (<20–21.5) (3 cases < 20 Du/L)	6	0.52% (0.16–1.66%)	7	−0.35 (−1.98 to −0.11%)	6

Abbreviations: Du/L DiviTum units per liter, mRNA Messenger RNA, TK1 Thymidine kinase 1
C1D1: after 28 days of anastrozole (with goserelin if premenopausal) monotherapy
C1D15: 2 weeks following the addition of daily palbociclib to anastrozole on cycle 1, day 1
Surgery without C5: surgery occurred after four cycles (each cycle is 28 days) of palbociclib plus anastrozole, followed by a washout of palbociclib for 3–5 weeks before surgery
Surgery with C5: cycle 5 (10–12 days of palbociclib) was administered immediately prior to surgery
^a p < 0.001 compared with the preceding time point using the Wilcoxon signed-rank test (a value of 20 Du/L was used to impute the measurements of TK1 under the detection limit of 20 Du/L)
^b p < 0.05 compared with the preceding time point using the Wilcoxon signed-rank test (a value of 20 Du/L was used to impute the measurements of TK1 under the detection limit of 20 Du/L)

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