Cytokeratin-19 and mammaglobin gene expression in circulating tumor cells from metastatic breast cancer patients enrolled in North Central Cancer Treatment Group (NCCTG) trials, N0234/336/436/437
Menée sur des échantillons sanguins prélevés chez 86 patientes atteintes d'un cancer métastatique du sein et incluses dans 4 essais cliniques américains, cette étude évalue la faisabilité de mesurer le niveau d'expression de deux gènes, CK-19 et MGB1, dans les cellules tumorales circulantes avant le traitement pour prédire la réponse thérapeutique
Purpose:To investigate the associations between baseline and post-treatment circulating tumor cell (CTC) gene expression and outcome of patients enrolled in four NCCTG metastatic breast cancer (MBC) trials where specimens were shipped (at 4°C) from community-based sites to a reference laboratory (Mayo Clinic-Rochester, MN). Experimental Design:Blood was collected at treating sites from MBC patients before (baseline), during, and at end of treatment with erlotinib+gemcitabine (N0234), sorafenib (N0336), irinotecan+cetuximab (N0436), or paclitaxel-poliglumex+capecitabine (N0437). CTCs were enriched from 10 mls of EDTA blood using CD45-depletion, 24-30 hours post-blood collection. Reverse transcription/quantitative PCR was used to determine cytokeratin-19 (CK19) and mammaglobin (MGB1) mRNA levels in CTCs from up to 13 (N0234), 16 (N0336), 18 (N0436), and 39 (N0437) patients. The gene expressions were normalized to β2-microglobulin and calibrated to healthy blood using the 2-ΔΔCq algorithm; positivity was defined as ≥2. Results:CK19+mRNA cells were detected in 56%-75% and MGB1+mRNA cells in 23%-38% of 86 patients at baseline. CK19+mRNA cells were detected in 30%-67% and MGB1+mRNA cells in 14%-64% of 110 post-baseline serial samples. The presence of baseline CK19+mRNA cells (p=0.01) but not MGB1+mRNA cells (p=0.14) was significantly associated with shorter overall survival. A decrease in MGB1+mRNA levels (baseline-week 8) appeared to be associated with clinical response (p=0.05). Conclusions:CTC gene expression analysis performed by a reference laboratory is feasible when blood is collected from treating sites and processed 24-30 hours post-collection. The presence of baseline CK19+mRNA CTCs was associated with poor prognosis; a decrease in MGB1+mRNA CTCs may help predict response to therapy of MBC patients.
Clinical Cancer Research , résumé, 2011