THE RELATIVE PROGNOSTIC-SIGNIFICANCE OF TOTAL CATHEPSIN-D AND HER-2 NEU ONCOGENE AMPLIFICATION IN BREAST-CANCER/

Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cance r patients diagnosed between 1989-1991. In 581 of these patients, tumo r HER-2/neu oncogene amplification was simultaneously determined. In a ''training-set'' of 313 patients, ''high'' TCD was associated with si gnificantly shorter disease-free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of a xillary nodes with tumor deposits, tumor size, histologic type and gra de, or hormone receptor levels. In the node-positive group, high TCD l evel was associated with HER-2/neu amplification. After a median follo w-up duration of 31 months, univariate analysis indicated that high TC D level was significantly associated with shorter DFS only in node-pos itive patients. The shorter DFS in association with high TCD levels wa s observed in both estrogen-receptor-positive and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was pre dictive of shorter DFS in node-positive patients only. Because of the short duration of follow-up, the significance of TCD in overall surviv al was not determined. We conclude that high tumor TCD in node-positiv e patients is predictive of shorter DFS, and is often associated with HER-2/neu amplification. The possibility exists that high tumor TCD ma y act in combination with Her-2/neu amplification to promote dissemina tion of metastases. (C) 1994 Wiley-Liss, Inc.