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Predictive factors in breast cancer

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In the processes of malignant transformation, tumor cell growth regulation, angiogenesis and metastasis, and the development of drug resistance, a large number of oncogenes, suppressor genes, proteases and their inhibitors are involved. In addition to the classical clinical prognostic factors, many of these molecular biological parameters are increasingly used as prognosticator and predictive factors for response to therapy, and recently also as targets for new biologic therapeutic strategies.

In nearly 2800 patients with primary breast cancer and in 830 patients with recurrent disease we investigated by univariate and multivariate analysis the prognostic and/or predictive value of a large series of more than 20 molecular biological factors. In patients with primary breast cancer c-myc amplification, TP53 mutation and increased expression of cathepsins and/or components of the urokinase-type plasminogen (UPA) activator system showed clear prognostic value. The most powerful predictive factors for a favorable response to endocrine therapy are ER, PgR, and PS2, while HER2-neu, EGF-R, TP53 mutation and expression, uPA and TK are associated with a poor response to tamoxifen. Mainly TP53 mutations, TS and MRP expression were associated with type of response to chemotherapy. Germ-line mutations in the breast cancer genes 1 and 2 (BRCA1/2) were associated with a similar prognosis as observed in patients with sporadic breast tumors in spite of different tumor characteristics (Verhoog et al, Lancet 1998 and J Clin Oncol 1999). Recently a new gene associated with tamoxifen resistance, located at human chromosome 16q, was detected in over 97 patients. High BCRA1/p130Cas protein levels were associated with poor prognosis (ES van der Flier et al, J Natl Cancer Inst 2000, 92:120-127).

In conclusion, an increasing number of cell biological factors such as HER2-neu appear to be of clinical importance because of their predictive value and their role as (potential) targets for therapy.

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Klijn, J., Berns, E., Dorssers, L. et al. Predictive factors in breast cancer. Breast Cancer Res 2 (Suppl 1), S.32 (2000).

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