Abstract
BackgroundIn breast cancer current guidelines do not recommend the routine use of serum tumour markers. Differently, we observed that CEA-TPA-CA15.3 (carcinoembryonic (CEA) tissue polypeptide (TPA) and cancer associated 115D8/DF3 (CA15.3) antigens) panel permits early detection and treatment for most relapsing patients. As high sensitivity and specificity and different cut-off values have been reported for mucin-like carcinoma associated antigen (MCA), we compared MCA with the above mentioned tumour markers and MCA-CA15.3 with the CEA-TPA-CA15.3 panel.MethodsIn 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, ≥ 11 and ≥ 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In addition, we compared the MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels.ResultsDistant metastases occurred 19 times in 18 (6.7%) of the 268 patients who were disease-free at the beginning of the study. MCA sensitivity with both cut-off values was higher than that of CEA or TPA or CA15.3 (68% vs 10%, 26%, 32% and 53% vs 16%, 42%, 32% respectively). With cut-off ≥ 11 U/mL, MCA showed the lowest specificity (42%); with cut-off ≥ 15 U/mL, MCA specificity was similar to TPA (73% vs 72%) and lower than that of CEA and CA15.3 (96% and 97% respectively). With ≥ 15 U/mL MCA cut-off, MCA sensitivity increased from 53% to 58% after its association with CA15.3. Sensitivity of CEA-TPA-CA15.3 panel was 74% (14 of 19 recurrences). Eight of the 14 recurrences early detected with CEA-TPA-CA15.3 presented as a single lesion (oligometastatic disease) (5) or were confined to bony skeleton (3) (26% and 16% respectively of the 19 relapses). With ≥ 11 U/mL MCA cut-off, MCA-CA15.3 association showed higher sensitivity but lower specificity, accuracy and positive predictive value than the CEA-TPA-CA15.3 panel.ConclusionAt both the evaluated cut-off values serum MCA sensitivity is higher than that of CEA, TPA or CA15.3 but its specificity is similar to or lower than that of TPA. Overall, CEA-TPA-CA15.3 panel is more accurate than MCA-CA15.3 association and can "early" detect a few relapsed patients with limited metastatic disease and more favourable prognosis. These findings further support the need for prospective randomised clinical trial to assess whether an intensive post-operative follow-up with an appropriate use of serum tumour markers can significantly improve clinical outcome of early detected relapsing patients.
Highlights
In breast cancer current guidelines do not recommend the routine use of serum tumour markers
The organs initially involved in the relapse were: bone (8), viscera (8), soft tissue (1), bone and viscera (2)
These findings and our results suggest that, mucin-like carcinoma associated antigen (MCA) and CA15.3 recognise distinct epitopes on the same molecule [36], in metastatic breast cancer cells MCA expression almost completely overlaps that of CA15.3, while it partially occurs among Carcinoembryonic antigen (CEA), TPA and CA15.3
Summary
In breast cancer current guidelines do not recommend the routine use of serum tumour markers. Methods: In 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, ≥ 11 and ≥ 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In randomised trials and meta-analysis intensive post-operative follow-up has been shown to be useful only in early diagnosis but not in improving clinical outcome and/or quality of life [1,2,3,4] In these trials clinical-instrumental was compared with clinical only follow-up and neither any serum tumour marker panel nor appropriate criteria for its use were adopted. 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) [58]. 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
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