The Feasibility of Irreversible Electroporation for the Treatment of Breast Cancer and Other Heterogeneous Systems
- 508 Downloads
Developments in breast cancer therapies show potential for replacing simple and radical mastectomies with less invasive techniques. Localized thermal techniques encounter difficulties, preventing their widespread acceptance as replacements for surgical resection. Irreversible electroporation (IRE) is a non-thermal, minimally invasive focal ablation technique capable of killing tissue using electric pulses to create irrecoverable nano-scale pores in the cell membrane. Its unique mechanism of cell death exhibits benefits over thermal techniques including rapid lesion creation and resolution, preservation of the extracellular matrix and major vasculature, and reduced scarring. This study investigates applying IRE to treat primary breast tumors located within a fatty extracellular matrix despite IREs dependence on the heterogeneous properties of tissue. In vitro experiments were performed on MDA-MB-231 human mammary carcinoma cells to determine a baseline electric field threshold (1000 V/cm) to cause IRE for a given set of pulse parameters. The threshold was incorporated into a three-dimensional numerical model of a heterogeneous system to simulate IRE treatments. Treatment-relevant protocols were found to be capable of treating targeted tissue over a large range of heterogeneous properties without inducing significant thermal damage, making IRE a potential modality for successfully treating breast cancer. Information from this study may be used for the investigation of other heterogeneous tissue applications for IRE.
KeywordsElectropermeabilization Cancer therapy Minimally invasive surgery Non-thermal ablation Bioheat transfer Tissue electroporation Tumor ablation Breast carcinoma Electrical conductivity
This work has been supported by The Coulter Foundation. We acknowledge the assistance of Erin Bredeman, Paulo Garcia, and Chris Arena and the technical help of Ravi Singh.
- 5.Clough, K. B. Oncoplastic surgery allows extensive resections for conservative treatment of breast cancer. Eur. J. Cancer 4:S119, 2006.Google Scholar
- 30.Lee, R. C., D. Zhang, et al. Biophysical injury mechanisms in electrical shock trauma. In: Annual Review of Biomedical Engineering, edited by M. L. Yarmish, K. R. Diller, and M. Toner. Palo Alto: Annual Review Press, 2000, pp. 477–509.Google Scholar
- 32.Miklavcic, D., D. Semrov, H. Mekid, and L. M. Mir. In vivo electroporation threshold determination. In: Proceedings of the 22nd Annual EMBS International Conference, Chicago, IL, 2000.Google Scholar
- 39.Preda, L., G. Villa, S. Rizzo, and L. Bazzi. Magnetic resonance mammography in the evaluation of recurrence at the prior lumpectomy site after conservative surgery and radiotherapy. Breast Cancer Res. 8:2006.Google Scholar
- 42.Sapareto, S. A. Thermal dose determination in cancer therapy. Radiother. Oncol. 10:787–795, 1984.Google Scholar
- 43.Sickles, E. A., and K. A. Herzog. Intramammary scar tissue: a mimic of the mammographic appearance of carcinoma. Am. J. Roentgenol. 135:349–352, 1980.Google Scholar
- 48.Weaver, J. C. Electroporation of biological membranes from multicellular to nano scales. IEEE Trans. Dielect. Elect. Ins. 754–768, 2003.Google Scholar