Surgical Oncology

The use of the selective estrogen receptor modulator tamoxifen in the treatment of breast cancer is associated with adverse effects on the endometrium such as discharge, bleeding, and endometrial cancer. Angiogenesis in the endometrium is under hormonal control. One of the most potent inducers of angiogenesis is vascular endothelial growth factor (VEGF), a protein which is increased in breast cancer tumors. Tamoxifen is also associated with higher plasma VEGF levels in patients whose breast cancer is in remission. Vitamin E succinate (VES) has been identified as an inhibitor of VEGF expression in breast, melanoma, and prostate cell lines. The objective of this project is to test the hypothesis that the addition of vitamin E succinate (VES), a putative inhibitor of angiogenesis, to tamoxifen therapy further decreases the size of estrogen receptor-positive human tumors in xenografted nude mice. VES is expected to have a similar effect on VEGF expression in ER-negative breast cancers and, if so, may offer an alternative to tamoxifen as a form of maintenance therapy. Lastly, co-adminstration of VES and tamoxifen may decrease the potential carcinogenic effect of tamoxifen on the uterus. Having demonstrated that VES reduced tumor growth and angiogenesis in the subcutaneously engrafted tumor models, we established a murine model of breast cancer metastatic to bone by arterial injection of tumor cells. This model will in turn use the treatment groups described above to evaluate the role of VES in prevention and treatment of breast cancer metastasis, particularly as an alternative to tamoxifen in estrogen receptor-negative tumors. An affirmative result would motivate clinical trials addressing a major problem in the adjuvant treatment of breast cancer.

Surgical Oncology Research

1. Interaction of Vitamin E Succinate and Tamoxifen in the Modulation of Angiogenesis in Breast Cancer
2. SIU Surgery Subspecialty - Family Practice Telehealth Collaboration
3. A Prospective Study to Evaluate The Risk of Local Relapse in Sentinel Lymph Node Negative Patients With Breast Cancer

Recent Manuscripts

Peralta E.A, Bailey LJ, Litwiller AR, Rogers LQ, Verhulst SJ and Gary L. Dunnington, M.D. Increased BMI Raises Breast Cancer Rate in Women with Gail Score Over 1.7. Arch Surg; submitted.
Schwarz RE, Hillebrand G, Peralta EA, Chu DZ, Weiss LM. Long-term survival after radical operations for cancer treatment-induced sarcomas: how two survivors invite reflection on oncologic treatment concepts. Am J Clin Oncol. 2002 Jun;25(3):244-7.
Peralta E.A., Ellenhorn,JDI, Wagman L.D. , Andersen, J.D., Chu, D.Z. Contralateral Prophylactic Mastectomy Improves the Outcome of Selected Patients with Breast Cancer, Am J Surg 2000;180:439-445.
Liu, X.P., Peralta E.A., Ellenhorn, J.D.I.,Diamond, D.J.
Targeting of Human p53 Over-Expressing Tumor Cells by an HLAA*0201-Restricted Murine T-Cell Receptor Expressed in Jurkat T Cells, Cancer Res. 2000 60:693- 701
Peralta E.A., McCarty T.M., Liu X.P., Wilson, T.G., Diamond D.J., and Ellenhorn J.D.I. Immunotherapy of Bladder Cancer Targeting p53. J.Urol. 1999 162(5):1806-11.
Schwarz, R.E., McCarty T.M., Peralta E.A., Ellenhorn J.D.I., An Orthotopic in vivo model of Human Pancreatic Cancer, Surgery, 1999 126:562-567.
Peralta E.A. and Yarington C.T., Malignant Melanoma of the Head and Neck: Effect of Treatment on Survival. Laryngoscope 1998;108(2):200-203.
Traverso L.W., Peralta E.A.,Ryan J.R., Kozarek RA, Intraductal Neoplasms of the Pancreas, Am. J. Surg. 1998 175 (5):426-432.
McCarty, T.M., Liu X., Sun J., Peralta E.A., Diamond D. J., and Ellenhorn J.D.I, Targeting p53 for Adoptive T Cell Immunotherapy,
Cancer Res. 1998 58 (12):2601-2605.

Abstracts / Posters

Engle DL, Litwiller AR, Rao NS, Peralta E A, Vitamin E succinate decreases tamoxifen-induced proliferation and VEGF expression in mouse uterus and human endometrial carcinoma. San Antonio Breast Cancer Symposium, San Antonio, TX, December 2, 2003.
So MJ, Engle DL and Peralta E A, Vitamin E acetate supplementation may be detrimental to tamoxifen efficiency. San Antonio Breast Cancer Symposium, San Antonio, TX, December 13, 2002
Peralta EA, Engle DL Uterine effects of tamoxifen and vitamin E succinate in a murine model of breast cancer. Proceedings of the American Society of Clinical Oncology 38th Annual Meeting,
21:(2)57b. Orlando, FL, May 18, 2002.
Peralta EA, Liu XP, Diamond DJ, Ellenhorn JDI., Transfer of a p53 specific T cell receptor from murine to human T cells. SSO Cancer Symposium, Orlando, FL, March 4, 1999.
Liu XP, Peralta EA, Diamond DJ, Ellenhorn JDI., Specific recognition of human p53 overexpressing tumor cells by an HLA
A2.1-restricted murine T cell receptor expressed in Jurkat T cells. AACR Annual Meeting, Philadelphia, PA, April 10, 1999.

Current Funding

Illinois Department of Public Health Penny Severns Breast and Cervical Cancer Research Fund: Interaction of vitamin E succinate and tamoxifen in the modulation of angiogenesis in breast cancer, July 2001 to present $41,000.