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Increase of CA 15.3 level during adjuvant chemotherapy in breast cancer. Sign of treatment efficacy?
- V. Pusceddu, B. Frau, M. Murgia, M.T. Ionta, L. Minerba, B. Massidda (1 March 2007)
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V. Pusceddu, Medical Oncologist Medical Oncology Department, Clinic University, 09100 Cagliari, Italy, B. Frau, M. Murgia, M.T. Ionta, L. Minerba, B. Massidda
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Although the American Society of Clinical Oncology and the most recent National Comprehensive Cancer Network guidelines do not recommended the routine monitoring of Ca 15.3 for early detection of breast cancer recurrence, the study of Keshaviah and Coll. [1] renews interest in its clinical use. Our thought is that Ca 15.3 can be useful both in the patient follow up and in treatment monitoring of patients with advanced disease. Moreover, the preoperative serum concentration of Ca 15.3 has been used as a prognostic factor in patients with node-negative and node-positive breast cancer showing that higher pre-operative levels of Ca 15.3 are related to worse prognosis [2], which may be due to a bigger tumor burden. In advanced disease, different studies have demonstrated that there is a kinetic pattern in changing Ca 15.3 levels during treatment. Following initiation of anti -cancer therapies, a transient initial rise in Ca 15.3 level can be observed, followed by a dropping off, not joined to progressive disease, probably due to the cytotoxic drugs effects on the tumor [3,4]. Moreover, in patients with early breast cancer, analysis of peripheral blood may help to monitor the process of dissemination of metastatic cells into vital organs by detection of circulating epithelial tumor cells (CETC). The CETC coming from the primary tumor retain biological characteristics, such as ER status, same response to therapies [5] and, probably, the ability to express mucins like Ca 15.3. We believe that patients with high-risk early breast cancer, could have, more likely, higher numbers of CETC, and with their lysis, following chemotherapy, would come a Ca 15.3 rise. We have experienced, in our clinical practice, that in some patients with early breast cancer, during adjuvant chemotherapy, there is a transient increase of Ca 15.3 levels. Our suggestion is that it could be a predictive factor of therapy efficacy. We measured the Ca 15.3 serum levels, during adjuvant chemotherapy, in 70 consecutive patients with early breast cancer (stage I-IIIB) correlating it with recurrence. Median follow up has been 21.8 months (13 - 51.8 months). The accepted normal range for Ca 15.3 levels in our Laboratory was 0-25 U/ml. The median Ca 15.3 level at baseline has been 22.86 U/ml (6-54 U/ml), whereas the maximum median level has been 35.64 U/ml ( 10-106 U/ml). We measured the variation rate of Ca 15.3 (median variation 28.29%) and then, we correlated it with recurrence. Up to October 2006, 15/70 patients (21.4%) recurred. Disease free survival (DFS) expected for all 70 patients was 40.8 months. By Cox analysis, correlating the marker variation rate with recurrence, we found that high variation rate of Ca 15.3 is related to a protective effect of chemotherapy as to recurrence (HR 0.12,P=0.091; SE 1.257; CI 95%). In terms of DFS, we’ve compared patients with Ca 15.3 variation rate higher or slower than 10%. We found that median DFS were 49.32 months versus 35.16 months, respectively (P=0.0017). The results oberved, even if in a group of patients too small to make conclusive remarks, indicate that a transient Ca 15.3 level increase, in patients with early breast cancer, during adjuvant chemotherapy, might be a sign of therapy efficacy, associated, in our patients, with better DFS. Ca 15.3 is definitely a good predictor for breast cancer recurrence, and, because of its role in providing prognostic information during adjuvant chemotherapy has not been widely studied, should be largely tested in prospective studies, as DFS predictive factor for patients with early breast cancer on adjuvant chemotherapy . REFERENCES 1.KESHAVIAH A., DELLAPASQUA S., ROTMENSZ N. et al. CA 15.3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. 2007- Annals of Oncology., on line January 20. 2.DUFFY MJ, DUGGAN C., KEANE R. et al. High Preoperative CA 15.3 Concentrations Predict Adverse Outcome in Node-Negative and Node-Positive Breast Cancer: Study of 600 Patients with Histologically Confirmed Breast Cancer. Clin. Chem. 50:3 (559-563) 2004. 3.TAMPELLINI M., BERRUTI A., BITOSSI R. et al. Prognostic significance of changes in CA 15.3 serum levels during chemotherapy in metastatic breast cancer patients. Breast Cancer Res Treat 2006 Aug; 98(3): 241-8. 4.SJOSTROM J., ALFTHAN H. JOENSUU H. et al. Serum tumor markers CA 15.3, TPA, TPS, hCGbeta and TATI in the monitoring of chemotherapy response in metastatic breast cancer. Scand J Clin Lab Invest. 2001; 61(6): 431-41. 5.ROBERTSON JFR, AGRAWAL A., GUTTERIDGE E. et al. Correlation of CA 15.3 levels with clinical response in advanced breast cancer (ABC) patients receiving fulvestrant. 2006- 42nd Proc Am Soc Clin Oncol, 24:641. 6.PACHMANN K., CAMARA O., LOBODASCH K. et al. Circulating tumor cells: tools for monitoring and targets for therapy. 2006- Proc Am Soc Clin Oncol, 24 : 617. Conflict of Interest:None declared |
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