Preoperative CA 15.3 and prognosis in primary breast cancer

Abstract

CA15.3 is a breast cancer-associated antigen encoded by the MUC-1 gene. The clinical applications of CA 15.3 are the monitoring of response in advanced breast carcinoma and the early detection of recurrences. We have investigated the prognostic value of CA 15.3 in primary breast cancer. Preoperative serum CA 15.3 was measured in 478 patients with early breast cancer. Positive CA 15.3 was defined as > 30 U/ml. CA 15.3 positivity was correlated with patient outcome in terms of disease-free survival (DFS). Seven per cent of patients had elevated serum CA 15.3. A positive association was found between CA 15.3 positivity and tumour size. Twenty-one per cent of the patients with T3 and T4 tumours had high serum concentrations of CA 15.3; while only six per cent of patients with T1 and T2 tumours had elevated concentrations of CA 15.3 (p < 0.0001). There was no correlation between CA 15.3 serum levels and menopausal status, axilary lymph node status, estrogen receptor status, p53 and erbB-2 status, and CEA serum levels. With a median follow-up of 24 months, we found that elevated CA 15.3 levels predicted a poor clinical outcome. The probability of disease-free survival at two years was 73% in patients with high preoperative CA 15.3 compared with 90% in patients with normal CA 15.3 levels (logrank p = 0.003). The association of CA 15.3 with DFS was also analysed with a Cox analysis, and was found to be independent of tumour size. The multivariate analysis showed that poor disease-free survival was significantly associated with high CA 15.3 (p = 0.04), large tumour size (p = 0.001), estrogen receptor negative status (p = 0.008), overexpression of erbB-2 (p = 0.04), and overexpression of p53 protein (p = 0.03).Preoperative serum CA 15.3 is significantly related to clinical outcome in patients with early breast cancer. High CA 15.3 indicates a poor prognosis and this is independent from tumour size. Whether the poor prognosis associated with CA 15.3 is related with the role of mucins in the adhesion of cancer cells needs to be investigated.