Aim of study was to summarize six-year institutional experience with serial evaluation of circulating CA15-3 antigen as a method of early detection of breast cancer relapse.
Material and methods: CA15-3 concentrations were assayed immuno-enzymatically in the sera of 733 women with breast carcinoma: in 707 cases marker was analyzed serially (every 4 months during follow-up after completion of radical treatment and when the relapse of breast cancer was clinically suspected) and in 26 patients--at diagnosis of locoregional relapse and\or breast cancer dissemination; 5493 assays of the CA15-3 antigen were performed in total. The cut-off limit was established at 30 u/ml. Results of CA15-3 tests were analyzed in relation to clinical status of the disease and dominant site of breast cancer relapse.
Results: 1) in patients with distant metastases (N = 149), mean serum CA15-3 values and the percentage of positive results were significantly higher as compared to cases with locoregional relapse and carcinoma of the contralateral breast (N = 54; p < 0.0001) and those without clinical evidence of relapse (N = 530; p < 0.0001), in agreement with previous studies; 2) the highest mean values of CA15-3 were observed in patients with liver and multiple metastases, lower in those with bone or lung secondaries, and the lowest when the metastatic involvement of supraclavicular nodes was noticed; 3) the CA15-3 sensitivity rates were higher in patients with liver or bone metastases (91.7% and 91.4%, respectively), as compared to those with multiple (79.5%) and lung (72.4%) secondaries, and the lowest when metastases in supraclavicular nodes (40.0%) or other organs (60.0%) were diagnosed; 4) the comparison of subjects with liver secondaries and those with other sites of breast cancer dissemination indicated statistically significant difference in the mean CA15-3 values (p < 0.0001) and the number of positive results of the test (p < 0.05); 5) the sensitivity rates of CA15-3 antigen for one, two, three and more skeletal metastases detected by bone scintigraphy were 50%, 100% and 100%, respectively (N = 30); 6) in 84 out of 116 (72.4%) patients with distant metastases, the increased CA15-3 concentration preceded the clinical diagnosis of the relapse with the median lead time 9 months (range: 1-40); 7) the highest positivity rates of the lead time were observed in patients with liver or lung metastases (93.8% and 81.0%, respectively) and the lowest one in those with multiple sites of metastases (43.0%).
Conclusion: The study confirmed the validity of serial CA15-3 assays in the early diagnosis of breast metastatic disease. It is worth to emphasize the high sensitivity of the CA15-3 test in detecting bone metastases (100% in patients with scintigraphically diagnosed two or more metastatic lesions), but the group of patients was too small to make our observation conclusive. In none of the studies published previously, the beneficial impact of serial CA15-3 assays during follow-up on survival and quality of life in breast cancer patients was clearly demonstrated. Thus, modifying treatment based solely on increasing marker levels is not recommended.