Identification of a unique biological tumor marker in human breast cyst fluid and breast cancer tissue

Breast cyst fluid from 35 women was stratified into risk groups based on personal and family history of breast cancer. Mitogenic activity in breast cyst fluid of women at highest risk to develop breast cancer was significantly higher than the activity in the lowest-risk group. There was a direct dose-dependent relationship between mitogenic activity and increased risk of developing breast cancer. Size-exclusion chromatography showed that breast cyst fluid from women at highest risk contained two peaks of growth factor activity: less than 6 kilodaltons (kd), identified as human EGF (epidermal growth factor), and 6 to 18 kd. Moderate-risk group samples demonstrated only the single less than 6 kd peak, whereas the lowest-risk group had insignificant growth-promoting activity. Breast cancer tissue analyzed in a similar manner revealed a predominant 6- to 14-kd peak of mitogenic activity demonstrating the same acid- and heat-stability found in breast cyst fluid.
In spite of an increasing emphasis on mammography (X-ray of the breast to detect cancer at an early stage) and self-examination, breast cancer rates continue to rise. Early diagnosis remains the best method of increasing optimally effective treatment. Tumor cells from cancers confined to the breast grow more slowly than cells from tumors that have spread to the axilla (armpit) or to other organs. It is possible that growth factors in breast cyst fluid contribute to the spread of malignancy. To determine whether the fluid in breast cysts could serve as a biological marker for subsequent malignancy, samples were taken from 35 women, and tissue culture tests were performed. The women were grouped into three categories by risk of developing breast cancer as a result of personal and family history of that disease. The tissue culture test measured the extent to which the cyst fluid promoted mitosis (cell division) in a well-characterized cell line. Additional studies were performed to evaluate the mitogenic activity of malignant tumors removed from other subjects during cancer treatment. Results showed a direct relationship between risk category and mitogenic activity; the cyst fluid from women at highest risk for developing cancer had the greatest mitogenic activity. Moreover, the three groups had a marked difference in mitogenic activity of the cyst fluid. Analyses of the cyst fluid samples showed that substances of two molecular weights comprised the mitogens. One of these weights corresponded to the point of greatest mitogenic activity from the cancer tissue samples that were also analyzed. Identification of a growth factor in breast cyst fluid could aid in predicting malignancy, as well as in evaluation of treatment effectiveness. Other implications of the findings are discussed. (Consumer Summary produced by Reliance Medical Information, Inc.)