The relative prognostic significance of total cathepsin D and HER-2/neu oncogene amplification in breast cancer. The South Australian Breast Cancer Study Group.
Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients diagnosed between 1989-1991. In 581 of these patients, tumor HER-2/neu oncogene amplification was simultaneously determined. In a "training-set" of 313 patients, "high" TCD was associated with significantly shorter disease-free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of axillary nodes with tumor deposits, tumor size, histologic type and grade, or hormone receptor levels. In the node-positive group, high TCD level was associated with HER-2/neu amplification. After a median follow-up duration of 31 months, univariate analysis indicated that high TCD level was significantly associated with shorter DFS only in node-positive patients. The shorter DFS in association with high TCD levels was observed in both estrogen-receptor-positive and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was predictive of shorter DFS in node-positive patients only. Because of the short duration of follow-up, the significance of TCD in overall survival was not determined. We conclude that high tumor TCD in node-positive patients is predictive of shorter DFS, and is often associated with HER-2/neu amplification. The possibility exists that high tumor TCD may act in combination with HER-2/neu amplification to promote dissemination of metastases.
Seshadri
R
R
Department of Hematology, Flinders Medical Centre, Bedford Park, South Australia.
Horsfall
D J
DJ
Firgaira
F
F
McCaul
K
K
Setlur
V
V
Chalmers
A H
AH
Yeo
R
R
Ingram
D
D
Dawkins
H
H
Hahnel
R
R
D000328:Adult; D000368:Aged; D001940:Breast / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000401:mortality; D002402:Cathepsin D / Q000032:analysis*; D016009:Chi-Square Distribution; D003600:Cytosol / Q000737:chemistry; D005260:Female; D005784:Gene Amplification; D006801:Humans; D015993:Life Tables; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009857:Oncogenes / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013021:South Australia / Q000453:epidemiology; D014904:Western Australia / Q000453:epidemiology
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D002402:Cathepsin D