Amir Kashefi

INTRODUCTION: Breast Cancer is the most common cancer in Iranian women. This study aims to demonstrate the characteristics of breast diseases- and especially breast cancer- according to pathologic records in Tehran, Iran. METHODS: In this cross-sectional study, all records of pathologic specimens (biopsy or mastectomy) categorized as "breast diseases" from 1996 to 2000 in five teaching hospitals in Tehran were studied. For each patient, sex, age, breast pathology, pathological staging of malignant lesions, side and location of the tumor and the type of surgery were reviewed by a trained general practitioner. SPSS version 10 was used for statistical analysis. RESULTS: The mean age of women with breast cancer was 48.8. The highest frequency of malignancies was observed in the 40-49 age group (31.8%). Twenty-three percent of breast cancers were observed in women younger than 40 years. About 83 percent of malignant lesions in women were in T2, T3 or T4 at diagnosis. Only about 4 percent of women with breast cancers had tumors in stage I or in-situ carcinomas. Nearly 70 percent of the cancers were detected only after lymph node involvement. Only 4.3 percent of our female cases had the chance of conservative mastectomy. Twenty-eight percent of specimens from biopsies in women were malignant. DISCUSSION AND CONCLUSION: In Iran, breast cancer affects women at least one decade younger than their counterparts in developed countries. A considerable proportion of our cases (96%) were in stage II or III at diagnosis. These results show advanced cases at presentation in Iran which further mandate a national cancer detection program involving more effective public education and encouragement of women for breast self-examination and participation in screening campaigns.

This study used integrin alpha v beta3 as a target for tumor-specific delivery of tumor necrosis factor-alpha (TNF). The fusion protein RGD4C-TNF bound specifically to alpha v beta3 as evidenced by cell receptor binding assay and noninvasive micro-positron emission tomography imaging. 64Cu-DOTA-RGD4C-TNF had significantly higher activity accumulation in integrin-positive tumors (U87MG and MDA-MB-435) but not in integrin-negative tumors (C6) compared with 64Cu-DOTA-TNF. The magnitude of tumor uptake of 64Cu-DOTA-RGD4C-TNF correlated well with the alpha v beta3 level (U87MG > MDA-MB-435 > C6). Tumor accumulation of 64Cu-DOTA-RGD4C-TNF could be effectively blocked by c(RGDyK) peptide in alpha v beta3-positive tumor models, suggesting alpha v beta3 specificity of RGD4C-TNF fusion protein in vivo. Furthermore, although the fusion of RGD4C moiety to TNF had little effect on the bioactivity and cytotoxicity of RGD4C-TNF compared with TNF in cell culture, RGD4C-TNF was significantly more potent than TNF in inhibiting orthotopic MDA-MB-435 tumor growth. Ex vivo tissue staining confirmed specific cytotoxicity of RGD4C-TNF against integrin-positive tumor cells and tumor vasculature.