Utility of a Serum Tumour Marker Panel in the Post-Operative Follow-Up of Breast Cancer Patients with Equivocal Conventional Radiological Examinations

Abstract

Objective: To assess the value of the serum carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and breast cancer-associated antigen CA15.3 (CEA-TPA-CA15.3) tumour marker panel in selecting from a group of patients with equivocal bone scintigraphy, chest X-ray or liver echography, those with skeletal, thoracic or liver metastases. Clinical data of 427 breast cancer patients submitted to an intensive follow-up after mastectomy between January 1986 and December 2000 were retrospectively reviewed. Methods: Among the 427 patients operated on for breast cancer, 221 patients with a total of 332 equivocal instrumental examinations (bone scintigraphy, n = 286; chest X-ray, n = 29; liver echography, n = 17) were reviewed. All 221 patients were followed up clinically, biochemically and instrumentally until there was a clear definition of their condition, metastatic or not, for an average time of 35 months. Positive and negative predictive values of the tumour marker panel in patients with equivocal bone scintigraphy, chest X-ray and liver echography were evaluated; concomitant clinical symptoms were also taken into consideration. Results: Among the 221 patients with equivocal bone scintigraphy, chest X-ray and liver echography, tumour markers showed a positive predictive value of 69, 93 and 83% and a negative predictive value of 98, 86 and 91%, respectively, for the indication of the metastatic or benign origin of the equivocal instrumental imaging. Clinical symptoms were not helpful in predicting metastatic disease (sensitivity, specificity and accuracy of 60, 53 and 54%, respectively). Conclusions: These data suggest that a short monitoring with the CEA-TPA-CA15.3 tumour marker panel is an important tool to confirm or exclude metastatic disease in those patients who are suspected to have metastases following common instrumental investigations, and it is particularly important to avoid false positive diagnoses.

Intensive post-operative follow-up of breast cancer patients with tumour markers: CEA, TPA or CA15.3 vs MCA and MCA-CA15.3 vs CEA-TPA-CA15.3 panel in the early detection of distant metastases

“…With regard to CEA, TPA and CA15.3, CA15.3 (with MCA cut-off value ≥ 11 UI/mL) and TPA (with MCA cut-off value ≥ 15 UI/mL) were more sensitive than both remaining indicators. However, only with ≥ 11 U/mL MCA cut-off value, sensitivity increased slightly (from 53% to 58%) after the association of MCA with CA15.3, while as we [4,7,9-11] and others [22,26,33] previously reported, it occurred significantly when TPA was associated with CA15.3 and CEA (Tables 1, 2). In other studies a range of MCA sensitivity similar to CA15.3 and no significant increase in sensitivity when MCA was combined with CA15.3 were found [14,27,34,35].…”

“…As previously reported [9-11] in our clinical practice only patients with CE or PI in one or more tumour markers, clearly unexplained by any other condition, are considered suspected of tumour relapse.…”

“…The reason for serial BS, LE and CXR examinations, even if more prolonged, was to detect asymptomatic relapses falsely negative with serum tumour markers, which as we have previously reported [4,7,9-11] are about 15–25% using CEA-TPA-CA15.3 tumour marker panel.…”

“…Different studies appropriately using serum tumour markers within an intensive post-operative follow-up showed that in many relapsing patients clinical-instrumental diagnosis was anticipated and that this anticipation permitted an earlier treatment which significantly prolonged disease-free survival (DFS) and/or overall survival (OS) [5-8]. Moreover we showed that this type of follow-up strongly reduced need for conventional radiological examinations [9-11]. Therefore, unlike current guidelines, it is routine practice in our center to carry out an intensive post-operative follow-up of breast cancer patients using both serum tumour markers and imaging techniques.…”

Biomarkers in breast cancer

“…Among them, only CA15.3 are considered clinically relevant. However, the last updated guidelines of the American Society of Clinical Oncology (ASCO) (30) do not recommend the use of any circulating tumour marker post-operatively as they are not considered sufficiently accurate to be used routinely. However, the last updated guidelines of the American Society of Clinical Oncology (ASCO) (30) do not recommend the use of any circulating tumour marker post-operatively as they are not considered sufficiently accurate to be used routinely.…”