Diagnostic ability of different human milk fat globule antigens in breast cancer

Abstract

Human mammary epithelial antigens (HME-Ags) are released into the circulation by breast tumors and not by normal breast tissue (Proc. Natl. Acad. Sci. USA 74: 582-586, 1977). This characteristic made them valuable, together with other breast cancer related antigens later identified, to develop immunoassays useful in the follow-up of breast cancer. Assays for these antigens in serum have less than complete sensitivity and partial specificity, and as a result of this have not been totally successful in studying the relapsing breast cancer patient. In the present work, correlations are made among 3 assays available for breast cancer disease follow-up. They detect HME-Ags, CEA, and the heavy molecular weight mucin of the human milk fat globule (HMFG). Values for sensitivity and specificity for the 3 assays were obtained from approximately 300 samples of patients whose clinical diagnosis at the time of blood drawing was rigorously established. A small but definite advantage in sensitivity is demonstrated for the HME-Ags assay over the other two. A similar advantage is also demonstrated in the sequential follow-up of breast cancer patients, where HME-Ags respond more rapidly in most instances to changes in tumor burden. Further, the ability of increases in levels of these assays to predict relapse was studied in 15 patients who relapsed. HME-Ags demonstrated a predictive value of 73%, while CEA and the heavy molecular weight mucin remained at 47%. The present study exemplifies the search for novel antigens (Ags) with maximal ability to detect breast cancer relapse and with improved sensitivity to monitor tumor burden changes. Here, assays for different antigens to be compared are tested in the same serum samples obtained from carefully staged patients. The results suggest a role as breast cancer markers for antigens of lower molecular weight than the epithelial mucin-like components studied previously.