Molecular biomarkers for breast cancer prognosis: Coexpression of c-erbB-2and p53

Objective To assess the prognostic significance of molecular biomarkers, pa rticularly c-erbB-2 and p53, through study of prospective clinical data and archival breast cancer tissues for women accrued to the Alabama Breast Can cer Project. Summary Background Data Defining molecular abnormalities in breast cancer i s an important strategy for early detection, assessment of prognosis, and t reatment selection. Evidence is strong that selective biomarkers, including c-erbB-2 and p53, have prognostic significance in breast cancer. Few studi es have analyzed the prognostic significance of coexpression of biomarkers. Methods Study patients were those accrued to the Alabama Breast Cancer Proj ect (1975-1978) who had archival breast cancer tissues available for analys is, Criteria for entrance into the Alabama Breast Cancer Project were T1-3 breast cancer with MO status. Age, nodal status, and histologic grade were also documented. Patients were randomized to radical versus modified radica l mastectomy, and node-positive patients were also randomized to adjuvant c hemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]) vers us melphalan. Archival breast cancer tissues were studied for c-erbB-2, TGF -alpha, p53, cathepsin D, bcl-2, and estrogen and progesterone receptor exp ression using immunohistochemistry. Survival curves were developed using th e Kaplan-Meier method. Univariate analysis was performed using the log-rank test, multivariate analysis using a rank regression model. Results Three hundred eleven patients were accrued to the Alabama Breast Ca ncer Project, and paraffin-embedded breast cancer tissues for 90 patients w ere available for immunohistochemical analysis of molecular biomarkers. Uni variate analysis showed nodal status, c-erbB-2 expression, and p53 expressi on to have prognostic significance, Coexpression of c-erbB-2 and p53 was al so found to have prognostic significance by the log-rank test, Multivariate analysis showed T stage, nodal status, c-erbB-2 expression, and p53 expres sion to have independent prognostic significance. Conclusions These data suggest that c-erbB-2 and p53 expression in breast c ancer have prognostic significance. After median follow-up of 16 years, coe xpression of c-erbB-2 and p53 may have more prognostic significance than tr aditional prognostic factors such as T stage and nodal status, Prospective study of large numbers of patients with breast cancer is encouraged to vali date these findings.