EXPRESSION OF RAS P21, P53 AND C-ERBB-2 IN ADVANCED BREAST-CANCER ANDRESPONSE TO FIRST LINE HORMONAL-THERAPY

Several oncogenes and tumour-suppressor genes have been identified tha t may have an important role in the development of human breast carcin oma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumour s with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncop roteins and clinical outcome in 92 patients with either locally advanc ed or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hor mone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured acco rding to UICC criteria after 6 months of treatment and all patients we re followed for time to progression and overall survival. As shown pre viously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progre ssion and overall survival. However, no statistically significant rela tionship existed between expression of ras p21, p53 or c-erbB-2 and re sponse to treatment, time to progression or overall survival. We concl ude that staining for these three oncoproteins has no role in therapeu tic decision-making in patients with advanced breast cancer. The negat ive finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variat ions in growth characteristics of advanced breast cancer may be influe nced by other factors.