Circulating CA 15-3 levels in the postsurgical follow-up of breast cancer patients and in non-malignant diseases.

Circulating CA 15-3 antigen levels were evaluated in patients with benign diseases and breast cancer patients with no clinical evidence of disease after surgery (NED). Patients with breast cancer NED were followed for tumor recurrence or death during a median of 12.9 months (range 1 to 25 months). CA 15-3 and carcinoembryonic antigen (CEA) were compared in the same breast cancer NED patient population. Elevated CA 15-3 levels (greater than 40 U/ml) were observed in 38 of 1220 patients with benign diseases (3.1%) and in 25 of 350 breast cancer NED patients (7.1%). Elevations of CEA (greater than 5 ng/ml) were observed in 23 patients with breast cancer NED (6.5%). Benign diseases that produced significant elevations of CA 15-3 were chronic hepatitis (42.9%), liver cirrhosis (13.3%), sarcoidosis (16.7%), tuberculosis (9.7%), and systemic lupus erythematosus (6.7%). In breast cancer NED, initial elevations of CA 15-3 were observed in 12 of the 297 patients that remained free of disease during the follow-up, and in 13 of the 40 patients that relapsed (4.0% vs. 32.5%, p less than 0.001). Initial CEA levels were elevated in 16 patients that remained NED and in 7 patients that relapsed (5.3% vs. 17.5%, p less than 0.001). Serial determinations of CA 15-3 in patients continuously NED showed persistent elevations in 4 cases. Three of these exhibited concomitant benign diseases. In relapsing patients, serial tumor marker determinations showed that elevations of CA 15-3 before any other clinical evidence of recurrence occurred significantly more frequently than elevations of CEA (45% vs. 25%, p less than 0.001). Overall, two or more serial elevated values of CA 15-3 were observed in 7 cases, and 6 of them (85%) eventually relapsed. Median survival from study entry was 18.3 months in patients with breast cancer NED that had initial elevated CA 15-3, compared to 25+ months in those with negative CA 15-3 (p less than 0.0001). We conclude that circulating levels of CA 15-3 antigen can be elevated in some patients with non-malignant diseases, and that serial determinations of CA 15-3 may be useful in the postsurgical follow-up of patients with breast cancer when specific types of benign diseases that may cause elevations of the antigen are excluded. Additionally, CA 15-3 is more sensitive than CEA in the early diagnosis of breast cancer recurrences, and the simultaneous assay of CEA does not add information to that of CA 15-3 alone.