[ Title ]
- Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients
[ Journal ]
- Int J Cancer
[ Author ]
- J. K. Madic, A.Bidard, F. C.Birzele, F.Ramey, G.Leroy, Q.Rio Frio, T.Vaucher, I.Raynal, V.Bernard, V.Lermine, A.Clausen, I.Giroud, N.Schmucki, R.Milder, M.Horn, C.Spleiss, O.Lantz, O.Stern, M. H.Pierga, J. Y.Weisser, M.Lebofsky, R.
[ Abstract ]
- Circulating tumor DNA (ctDNA) is a new circulating tumor biomarker which might be used as a prognostic biomarker in a way similar to circulating tumor cells (CTCs). Here, we used the high prevalence of TP53 mutations in triple negative breast cancer (TNBC) to compare ctDNA and CTC detection rates and prognostic value in metastatic TNBC patients. Forty patients were enrolled before starting a new line of treatment. TP53 mutations were characterized in archived tumor tissues and in plasma DNA using two next generation sequencing (NGS) platforms in parallel. Archived tumor tissue was sequenced successfully for 31/40 patients. TP53 mutations were found in 26/31 (84%) of tumor samples. The same mutation was detected in the matched plasma of 21/26 (81%) patients with an additional mutation found only in the plasma for one patient. Mutated allele fractions ranged from 2 to 70% (median 5%). The observed correlation between the two NGS approaches (R(2) = 0.903) suggested that ctDNA levels data were quantitative. Among the 27 patients with TP53 mutations, CTC count was >/=1 in 19 patients (70%) and >/=5 in 14 patients (52%). ctDNA levels had no prognostic impact on time to progression (TTP) or overall survival (OS), whereas CTC numbers were correlated with OS (p = 0.04) and marginally with TTP (p = 0.06). Performance status and elevated LDH also had significant prognostic impact. Here, absence of prognostic impact of baseline ctDNA level suggests that mechanisms of ctDNA release in metastatic TNBC may involve, beyond tumor burden, biological features that do not dramatically affect patient outcome.