Geburtshilfe Frauenheilkd 2011; 71 - M_15
DOI: 10.1055/s-0031-1286432

Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay

FA Taran 1, A Hartkopf 1, H Seeger 1, M Zwirner 1, D Wallwiener 1, H Neubauer 1, TN Fehm 1
  • 1Department of Obstetrics and Gynecology, University of Tuebingen, Tuebingen, Germany

Introduction:

The NeoAzure study has demonstrated that the use of the bisphosphonate zole-dronate in the neoadjuvant setting increases the rate of complete response in primary breast cancer and therefore indicates direct antitumor activity (Coleman et al. 2010). The purpose of this study was to compare the antitumor effect of zolendronic acid with standard chemotherapy in primary breast cancer cells using ATP-tumor chemosensitivity assay (ATP-TCA).

Methods:

Breast cancer tissues were obtained from patients with breast cancer who underwent primary breast cancer surgery at our institution between 2006 through 2009. Antitumor effects of zoledronic acid (Zol), TAC (Docetaxel, Adriamycin, Cyclophosphamide) and FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide) were tested in 116 fresh human primary breast cancer specimens using ATP-TCA. ATP-TCA results were analyzed with different cut-off levels for the half maximal inhibitory concentration (IC50) and for IC90 and for the sensitivity index (IndexSUM). Each single agent or combination was tested at six doubling dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations (TDC) derived from the plasma peak concentrations determined by pharmacokinetic data. The assay was carried out in duplicate wells with positive and negative controls.

Results:

The median IndexSUM value was lower for Zol (170) than for the combined regimen FEC (296) and TAC (195), respectively, indicating increased direct antitumor activity of Zol in primary breast cancer cells. The difference regarding IndexSUM between Zol and FEC was significant (p<0.05). The median IC50 value for Zol (8.03% TDC) was significantly lower than the IC50 values for FEC (33.5% TDC) and TAC (19.3% TDC) treatment (p<0.05). However, the median IC90 value for Zol (152.5% TDC) was significantly higher than the IC90 value obtained with TAC (49.5% TDC; p<0.05), but similar to the IC90 value for FEC (180.9% TDC).

Conclusions: Zol has a direct strong antitumor effect on primary breast cancer cells in vitro which is comparable to the antitumor effect of commonly used chemotherapeutic regimens in breast cancer. The clinical consequences have to be discussed.