Correlation of selected molecular markers to in vitro chemo sensitivity of node-negative primary human breast cancer

Abstract

9667 Background: The present study explores the correlation of the erbB oncogenes family and c-myc average gene copy numbers (AGCN) determined by ddPCR, topoisomerase 2 alpha (topo2), PAI, erbB-2, uPA genes mRNA expression, determined by RT-PCR, and Her-2 protein expression (Hercept test) to the ex vivo chemo sensitivity of the tumor cells in four drug regimens: combination of epirubicin and cyclophosphamide (EC), mitoxantrone (Mit), combination of paclitaxel and epirubicin (ET), and docetaxel and epirubicin (EDoc). Methods: A group of 741 female primary breast cancer (BC) was assessed. Among them 442 patients were node-negative (N-) and 299 node-positive (N+). The cancer cell cultures were treated with EC, Mit, ET, and Edoc, each in six different drug concentrations in the modified ATP-CVA assay. AUC values were calculated using trapezoidal rule. Chemo sensitivity was defined as AUC of more then 18000. Results: No significant correlations were found between all studied parameters and chemo sensitivity to all tested drug combinations in the whole group of BC samples, regardless the nodal status. However, in the group of N- BC, PAI mRNA expression negatively correlates with chemo sensitivity to EDoc (Spearman rank test R=-0.39; p=0.005) and erbB-2 mRNA expression positively correlates to Mit (R=0.34; p=0.02) in the subgroup of estrogen/progesterone negative samples (tested by means of IHC). Conclusions: mRNA expression of PAI and erbB-2 may be important factors differentially related to adjuvant chemo responsiveness, at least in the node-negative and hormone receptors-negative BC patients. No significant financial relationships to disclose.