Prognostic value of total cathepsin D in breast tumors

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Abstract
Evaluation of prognostic factors for breast cancers is important for therapeutic decisions both at the time of surgery and during postoperative surveillance. In 1979, H. Rochefort described an induced protein with a molecular weight of 52,000 Daltons identified as procathepsin D. Total cathepsin D (TCD) (52K + 48K + 34K), expressed in pmol/mg protein, can be measured by an immunoradiometric method commercialized by Cis-Biointernational. Total cathepsin D was assayed in 413 breast cancer tumors from patients who underwent surgery between January 1, 1978, and December 31, 1985. Using a cut-off of 35 pmol/mg protein, patients with an elevated level had a significantly poorer survival than those with a low level (p=0.03). This difference was not found for node-negative patients but was very significant for node-positive patients (p<0.008). The survival of node-positive patients with a low total cathepsin level was not statistically different from that of node-negative patients. Analysis of the N+ subgroup of patients who did not receive adjuvant chemotherapy revealed that TCD no longer had any prognostic value, whereas it was still important for the N+ subgroup who received an adjuvant treatment. Cox multivariate analysis of prognostic value for survival placed total cathepsin D in third position, after nodal invasion and progesterone receptor status, for the entire population, and in first position before progesterone receptor status for the node-positive population. The association of a low cathepsin level and positive progesterone receptors characterized the subgroup of patients with the longest survival. TCD levels played the same role for prediction of the outcome of metastasis. In conclusion, assays of total cathepsin D in tumor cytosols provide valuable prognostic information for breast cancer patients with nodal involvement at the time of diagnosis.