Abstract
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.
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Al-Sakere, B., F. Andre, C. Bernat, E. Connault, P. Opolon, R. V. Davalos, B. Rubinsky, and L. M. Mir. Tumor ablation with irreversible electroporation. PLoS ONE 2:e1135, 2007.
Al-Sakere, B., C. Bernat, F. Andre, E. Connault, P. Opolon, R. V. Davalos, and L. M. Mir. A study of the immunological response to tumor ablation with irreversible electroporation. Technol. Cancer Res. Treat. 6:301–305, 2007.
Bowman, H. F. Heat transfer and thermal dosimetry. J. Microw. Power 16:121–133, 1981.
Cady, B. Breast cancer in the third millennium. Breast J. 6:280–287, 2000.
Clough, K. B. Oncoplastic surgery allows extensive resections for conservative treatment of breast cancer. Eur. J. Cancer 4:S119, 2006.
Davalos, R. V., L. M. Mir, and B. Rubinsky. Tissue ablation with irreversible electroporation. Ann. Biomed. Eng. 33:223–231, 2005.
Davalos, R. V., B. Rubinsky, and L. M. Mir. Theoretical analysis of the thermal effects during in vivo tissue electroporation. Bioelectrochemistry 61:99–107, 2003.
Diller, K. R. Advances in heat transfer. In: Bioengineering Heat Transfer, edited by Y. I. Choi. Boston: Academic Press, 1992, pp. 157–357.
Dowlatshahi, K., D. Francescatti, and K. Bloom. Laser therapy for small breast cancers. Am. J. Surg. 184:359–363, 2002.
Edd, J. F., and R. V. Davalos. Mathematical modeling of irreversible electroporation for treatment planning. Technol. Cancer Res. Treat. 6:275–286, 2007.
Edd, J. F., L. Horowitz, R. V. Davalos, L. M. Mir, and B. Rubinsky. In vivo results of a new focal tissue ablation technique: irreversible electroporation. IEEE Trans. Biomed. Eng. 53:1409–1415, 2006.
Esser, A. T., K. C. Smith, T. R. Gowrishankar, and J. C. Weaver. Towards solid tumor treatment by irreversible electroporation: intrinsic redistribution of fields and currents in tissue. Technol. Cancer Res. Treat. 6:261–273, 2007.
Fedorcik, G. G., R. Sachs, and M. A. Goldfarb. Oncologic and aesthetic results following breast-conserving therapy with 0.5 cm margins in 100 consecutive patients. Breast J. 12:208–211, 2006.
Field, S. B., and C. C. Morris. The relationship between heating time and temperature: its relevance to clinical hyperthermia. Radiother. Oncol. 1:179–183, 1983.
Fisher, B., C. Redmond, R. Poisson, et al. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N. Engl. J. Med. 320:822–828, 1989.
Fitzal, F., M. Mittleboeck, H. Trischler, and W. Krois. Breast-conserving therapy for centrally located breast cancer. Ann. Surg. 247:470–476, 2008.
Franquet, T., C. D. Miguel, R. Cozcolluela, and L. Donoso. Spiculated lesions of the breast: mammographic-pathologic correlation. RadioGraphics 13:841–852, 1993.
Gautherie, M., Y. Quenneville, and C. M. Gros. Metabolic heat production, growth rate, and prognosis of early breast carcinomas. Biomedicine 22:328–336, 1975.
Giering, K., I. Lamprecht, O. Minet, and A. Handke. Determination of the specific heat capacity of healthy and tumorous human tissue. Thermochim. Acta 251:199–205, 1995.
Gomez-Iturriaga, A., L. Pina, M. Cambeiro, and R. Martinez-Monge. Early breast cancer treated with conservative surgery, adjuvant chemotherapy, and delayed accelerated partial breast irradiation with high-dose-rate brachytherapy. Brachytherapy 7:310–315, 2008.
Hibino, M., H. Itoh, and K. J. Kinosita. Time course of cell electroporation as revealed by submicrosecond imaging of transmembrane potential. Biophys. J. 64:1789–1800, 1993.
Janzen, N. K., K. T. Perry, K.-R. Han, B. Kristo, S. Raman, et al. The effects of intentional cryoablation and radio frequency ablation of renal tissue involving the collecting system in a porcine model. J. Urol. 173:1368–1374, 2005.
Jemal, A., R. Tiwari, T. Murray, et al. Cancer statistics 2004. CA Cancer J. Clin. 54:8–29, 2004.
Johns, P. C., and M. J. Yaffe. X-ray characterisation of normal and neoplastic breast tissues. Phys. Med. Biol. 32:675–695, 1987.
Jossinet, J. Variability of impedivity in normal and pathological breast tissue. Med. Biol. Eng. Comput. 34:346–350, 1996.
Kontos, M., E. Felekouras, and I. S. Fentiman. Radiofrequency ablation in the treatment of primary breast cancer: no surgical redundancies yet. Int. J. Clin. Pract. 62:816–620, 2008.
Krassowska, W., G. S. Nanda, M. B. Austin, and S. B. Dev. Viability of cancer cells exposed to pulsed electric fields: the role of pulse charge. Ann. Biomed. Eng. 31:80–90, 2003.
Lee, R. C. Cell injury by electric forces. Ann. NY Acad. Sci. 1066:85–91, 2005.
Lee, E. W., C. T. Loh, and S. T. Kee. Imaging guided percutaneous irreversible electroporation: ultrasound and immunohistological correlation. Technol. Cancer Res. Treat. 6:287–293, 2007.
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.
Maor, E., A. Ivorra, J. Leor, and B. Rubinsky. The effect of irreversible electroporation on blood vessels. Technol. Cancer Res. Treat. 6:307–312, 2007.
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.
Mir, L. M. Therapeutic perspectives of in vivo cell electropermeabilization. Bioelectrochemistry 53:1–10, 2000.
Mir, L. M., and S. Orlowski. Mechanisms of electrochemotherapy. Adv. Drug Deliv. Rev. 35:107–118, 1999.
Mir, L. M., S. Orlowski, J. J. Belehradek, J. Teissie, and M. P. Rols. Biomedical applications of electric pulses with special emphasis on antitumor electrochemotherapy. Bioelectrochem. Bioenerg. 38:203–207, 1995.
Ng, E. Y. K., and N. M. Sudharsan. An improved three-dimensional direct numerical modeling and thermal analysis of a female breast with tumor. Proc. IME. H. J. Eng. Med. 215:25–37, 2001.
Onik, G., P. Mikus, and B. Rubinsky. Irreversible electroporation: implications for prostate ablation. Technol. Cancer Res. Treat. 6:295–300, 2007.
Perez, C. A., and S. A. Sapareto. Thermal dose expression in clinical hyperthermia and correlation with tumor response/control. Cancer Res. 44:4818s–4825s, 1984.
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.
Rubinsky, B., G. Onik, and P. Mikus. Irreversible electroporation: a new ablation modality—clinical implications. Technol. Cancer Res. Treat. 6:37–48, 2007.
Sabel, M. S., C. S. Kaufman, P. Whitworth, H. Change, L. H. Stocks, R. Simmons, and M. Schultz. Cryoablation of early-stage breast cancer: work-in-progress report of a multi-institutional trial. Ann. Surg. Oncol. 11:542–549, 2004.
Sapareto, S. A. Thermal dose determination in cancer therapy. Radiother. Oncol. 10:787–795, 1984.
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.
Singletary, S., B. Fornage, N. Sneige, et al. Radiofrequency ablation of early-stage invasive breast tumors: an overview. Cancer J. 8:177–180, 2002.
Skinner, M. G. A theoretical comparison of energy sources—microwave, ultrasound and laser—for interstitial thermal therapy. Phys. Med. Biol. 43:3535, 1998.
Surowiec, A. J., S. S. Stuchly, J. R. Barr, and A. Swarup. Dielectric properties of breast carcinoma and the surrounding tissues. IEEE Trans. Biomed. Eng. 35:257–263, 1988.
Weaver, J. C. Electroporation: a general phenomenon for manipulating cells and tissue. J. Cell. Biochem. 51:426–435, 1993.
Weaver, J. C. Electroporation of biological membranes from multicellular to nano scales. IEEE Trans. Dielect. Elect. Ins. 754–768, 2003.
Weaver, J. C., and Y. A. Chizmadzhev. Theory of electroporation: a review. Bioelectrochem. Bioenerg. 41:135–160, 1996.
Werner, J., and M. Buse. Temperature profiles with respect to inhomogeneity and geometry of the human body. J. Appl. Physiol. 65:1110–1118, 1988.
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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.
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Neal, R.E., Davalos, R.V. The Feasibility of Irreversible Electroporation for the Treatment of Breast Cancer and Other Heterogeneous Systems. Ann Biomed Eng 37, 2615–2625 (2009). https://doi.org/10.1007/s10439-009-9796-9
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DOI: https://doi.org/10.1007/s10439-009-9796-9