Fol. Biol. 2012, 58, 185-192

https://doi.org/10.14712/fb2012058050185

Low Expression of NQO1 Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients Treated with TAC Regimen

Jiří Grim1, P. Jandík2, I. Slánská1, E. Doleželová-Brčáková3, L. Fuksa3, A. Ryška4, J. Knížek5, J. Petera1, S. Mičuda3, H. Hornychová4

1Department of Oncology and Radiotherapy, Charles University in Prague, Faculty of Medicine and University Teaching Hospital in Hradec Králové, Czech Republic
2Department of Surgery, Charles University in Prague, Faculty of Medicine and University Teaching Hospital in Hradec Králové, Czech Republic
3Department of Pharmacology, Charles University in Prague, Faculty of Medicine in Hradec Králové, Czech Republic
4Department of Pathology, Charles University in Prague, Faculty of Medicine and University Teaching Hospital in Hradec Králové, Czech Republic
5Department of Medical Biophysics, Charles University in Prague, Faculty of Medicine in Hradec Králové, Czech Republic

Received February 2012
Accepted May 2012

The aim of this study was to evaluate preoperative tumour expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) along with other biological markers as potential predictors of pathological complete response (pCR) to neoadjuvant docetaxel, doxorubicin, and cyclophosphamide-containing (TAC) chemotherapy in patients with primary breast cancer. Sixty-one patients who received neoadjuvant chemotherapy (NCT) with TAC regimen were enrolled in this prospective study. The preand postNCT expression of oestrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 and 2 (EGFR and HER2), NQO1, Ki-67 proliferation index, multidrug resistance protein 1 (MDR1), p53 and BCL2 were evaluated by immunohistochemistry. The pCR was reached in 14 patients (23 % of the study group). Multivariate analysis demonstrated that patients with ER-, PR-, NQO1negative, and Ki‐67‐positive tumours had a significantly higher chance to achieve pCR. Within the biological subtypes, the highest pCR rate (50 %) was seen in triple-negative (i.e. ER-, PR-, HER2-) tumours. Post-operative evaluation showed that in comparison to pre-operative tissue samples, NQO1 expression was significantly increased, while Ki‐67 and HER2 decreased, in the residual tissue after NCT. In conclusion, the present data suggests that NQO1 expression may be a novel diagnostic biomarker for the prediction of positive response to NCT in patients with breast cancer.

Funding

This study was supported by grant from the Ministry of Health of the Czech Republic IGA NS/10373-3/2009.

References

37 live references