Significance of Breast Carcinoma-associated Antigens as a Monitor of Tumor Burden: Characterization by Monoclonal Antibodies1

Use of monoclonal antibodies (Me 3 and Me 8) prepared against human mammary-epithelial antigens of human milk fat globule mem branes has enabled characterization of breast carcinoma (BC) associated antigens (BCAA), antibodies, and circulating immune complexes (CIC). For this study, BC patients were grouped on the basis of measurable tumor burden: Group I patients with no evidence of disease at sampling time; Group II patients with tumor burden £5g; and Group III patients with known regional or distal métastases. In an in vitro simulation of tumor burden change, selected BC patients1 sera were admixed with Me 3 and Me 8 at optimal concentration. CIC reduction (dissociation) for Groups I and III and increment (formation) for Group II were noted. Unlike Group I sera, Groups II and III sera required 4to 16-fold dilution of Me 3 and 4-fold more concentrated Me 8 to achieve maximal CIC changes. Serum BCAA isolated by use of both Me 3 and Me 8 immunobead procedures showed apparent Vf, 33,000 monomer, 66,000 dimer, and 95,000 trimer. When BCAA were added to BC patients' sera, autologous combinations resulted in small (7.7S) CIC for Groups I and III, and medium (9 to 12S) CIC for Group II. Conversely, allogenic combinations resulted in mainly small CIC for Group I, and intermediate CIC for Group II and Group III. Evaluation of circulating BCAA concen tration by use of a three-step radioligand technique demonstrated signif icant discrimination between BC patients' sera (mean = 105 ng/ml) and normal control sera (=20 ng/ml). BCAA were found to be elevated in 31 of 46 (67%) Group I (mean = 70 ng/ml), 41 of 43 (95%) Group II (mean = 197 ng/ml), and 30 of 46 (65%) Group III (mean = 50 ng/ml) patients' sera, as compared to "background" levels in malignant melanoma and normal controls. Benign breast disease sera showed moderate BCAA increases (mean = 48 ng/ml) in 20 of 35 (57%) patients. Furthermore, serial sample determination of BCAA in 36 selected BC patients con firmed the above pattern, indicating that this assay can be used with some restriction to monitor tumor burden. Whereas in early breast carcinoma increase in BCAA concentration was concurrent with or ante dated clinical objective evidence of tumor burden increase, significant decreased BCAA concentration was observed with tumor burden reduc tion. Overall, increased BCAA levels were associated with limited tumor burden (Group II) while decreased BCAA levels were observed with no evidence of disease (Group I) and known regional or distal metastatic advanced disease (Group III) during patients' follow-up.