Cathepsin D and prognosis in breast cancer

Article Abstract:

The ability to predict which patients with breast cancer are likely to be at high risk for recurrence of the disease could be important in planning the clinical treatment of these patients. In 1979 a glycoprotein (combination of protein and carbohydrate) was identified as being secreted by human breast cancer cells grown in laboratory tissue cultures. After purification the molecule, called cathepsin D, was identified as the precursor of an enzyme which acts to break down a protein (i.e., a protease). It was found that this compound is stimulated by the level of female hormones or estrogens, and its level was restricted by anti-estrogen drugs (which oppose estrogens). A classification system for the prognosis of breast cancer patients is related to the degree of cancerous involvement of the lymph nodes; no involvement indicates a better prognosis, and cancer spread to lymph nodes carries a poorer prognosis. In this experiment, tissues taken from 199 node-positive and 198 node-negative breast cancer patients were analyzed for the level of cathepsin D. The level of this compound was found to be a good predictor of the rate of recurrence in women who were node-negative, but not in those patients who were node-positive. In node-negative women the level of cathepsin D corresponded to the irregular number of chromosomes present within tumor cells (aneuploidy). Women with a high level of cathepsin D had a rate of recurrence which was 2.6 times greater than those having a low level. Cathepsin D may be useful in identifying women who have an elevated risk of cancer recurrence, and therefore require more aggressive therapy. (Consumer Summary produced by Reliance Medical Information, Inc.)

Measurement, Cathepsins

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Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry

Article Abstract:

In approximately half of the women diagnosed with breast cancer, the disease is restricted to the breast itself, with no evidence of cancer cells found in the neighboring lymph nodes. The availability of early breast cancer detection has made the diagnosis of more node-negative cancers. Even though the prognosis is good, 30 percent of the women with no nodal involvement die from the cancer. Treatment of node-negative breast cancers is controversial, and some practitioners give extra therapy. Factors influencing prognosis may help physicians select those patients who would benefit the most from such potentially toxic additional therapy. Diseased tissue in 395 frozen samples was analyzed for specific cell type and behavior by DNA flow-cytometry. Patients with aneuploid (cells with abnormal amount of chromosomes) tumors had five-year survival rates of 74 percent, compared with 88 percent among patients with diploid tumors (normal number of chromosomes). In the latter case, low S-phase fractions (a specific synthesis phase of a cell cycle) indicated 90 percent survival at five years and high values indicated a survival of 70 percent. This method of evaluating the characteristics of tumor cells is a meaningful indicator of survival of node-negative breast cancer patients. Patients with diploid, low S-phase tumors have good prognosis and may not be good candidates for adjuvant therapy.

Analysis, DNA, Flow cytometry

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Prognostic factors and treatment decisions in axillary-node-negative breast cancer

Article Abstract:

Of the estimated 186,000 cases of breast cancer that will be diagnosed in 1992, two-thirds will be node-negative; that is, the cancer will not have spread to the lymph nodes under the arm. Since 70% of these women can be cured without chemotherapy, this treatment should be limited to those who have a high risk of cancer recurrence. This can be determined using several prognostic factors. Several studies have shown that the smaller the tumor, the greater the long-term survival and duration of life cancer-free. Certain histologic types, such as ductal carcinoma in situ, also have a good prognosis. The presence or absence of estrogen receptors in the tumor may be useful when combined with other factors. Abnormal DNA content may or may not indicate a worse prognosis, but tumors that are actively proliferating have a worse prognosis. Excessive levels of the enzyme cathepsin D are associated with high cancer recurrence and poor survival. Once a woman's prognostic factors have been identified, treatment can be tailored accordingly.

Identification and classification, Tumors

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