Abstract
Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. 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 tumours 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 oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.
Highlights
Keywor: breast cancer, hormonal therapy: oestrogen receptor status: ki 67: epidermal growth factor receptor; c-erbB-2: p53: ras p21
Patients were assssed for complete response, partial response, static disease and progression according to Union Against Cancer (UICC) criteria (Hayward et al, 1977)
ER negativity, progesterone receptor (PR) negativity, a high Ki67 labelling index and positive epidermal growth factor receptor (EGFR) staining all correlated with progression of disease on hormonal therapy
Summary
1260 Human c-erbB-2 encodes for a receptor-like transmembrane glycoprotein, p185, which has tyrosine protein kinase activity and shares homology with the EGFR. Overexpression of c-erbB-2 protein in the primary tumours of patients with positive lymph nodes has been confirmed in a number of studies to be a marker of poor prognosis (Anbazhagan et al, 1991; Lovelin et al, 1991; O'Reilly et al, 1991; Gullick et al, 1991; Gusterson et al, 1992). C-erbB-2 has been reported to be a marker of poor prognosis in breast cancer patients with negative lymph nodes (Gullick et al, 1991; Wmstanley et al, 1991), in other studies the difference did not reach statistical significanc (Lovekin et al, 1991; O'Reilly et al, 1991; Gusterson et al, 1992). We studied the relationship between immunostaining for ras p21, p53 and c-erbB-2 and dinical outcome in a group of patients with advanced breast cancer who received hormonal therapy as their first- line treatment. We aseed staining of the more established ER (Nicholson et al, 1991), progesterone receptor (PR), the proliferative marker Ki67 (Nicholson et al, 1991) and EGFR (Nicholson et al, 1993, 1994) in the same patients
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