CA15-3 is a useful serum tumor marker for diagnostic integration of hybrid positron emission tomography with integrated computed tomography during follow-up of breast cancer patients

Abstract

Background: The aim of this study was to evaluate the value of CA15-3 for the diagnostic integration of molecular imaging findings performed with hybrid positron emission tomography and computed tomography (PETCT) technology.

Methods: We retrospectively selected 45 patients with a median age of 60 years (range 39-85 years) and a previous history of breast cancer (BC) who had already been treated with surgery and other treatments. Three measurements of CA15-3 were collected within 1 year before PETCT examination, at 6-9 months 3-6 months and 0-3 months before PETCT. The prolonged clinical outcome or imaging follow-up was used to define disease relapse. An increase in tumor marker value was compared with PETCT findings and disease relapse. Sensitivity and specificity for both tests were calculated with respect to clinical outcome.

Results: Disease relapse was detected in 16 out of 45 BC patients. CA15-3 and PETCT showed 75% sensitivity with a specificity percentage of 76% for CA15-3 and 79% for PETCT. Serum CA15-3 expression levels were significantly higher in BC patients with multiple metastatic sites with hepatic involvement. Analysis of serial CA15-3 serum levels showed an increase in CA15-3 3-6 months before PETCT could identify BC patients at risk for relapse (AUC = 0.81). Moreover, patients receiving anti-hormonal or chemotherapy medications with negative PETCT and positive CA15-3 relapsed after a median time of 158 days compared to patients who were negative for both tests and who were free from disease for at least 1 year.

Conclusions: Our results showed that serial increases in CA15-3 can be used to predict positive PETCT results in BC patients during follow-up. Increased levels of CA15-3 may be considered an early warning sign in patients needing accurate molecular imaging investigations, as they are at higher risk of recurrence. In cases of elevated levels, multiple lesions or liver involvement may exist. Also, patients receiving chemotherapeutic or anti-hormonal treatment who have negative PETCT scans and increased CA15-3 serum levels should be considered at risk for relapse, because the CA15-3-linked biochemical signal of the presence of a tumor can predict positive metabolic imaging.

Figure 1

Correlation between the trend in serial CA15-3 measurements and PETCT findings. The bar plot shows the mean CA15-3 serum levels at 0–3, 3–6, and 6–9 months prior to PETCT. Dotted line indicates CA15-3 cut-off (25 UI/mL). The P-value was determined with an unpaired t-test.

Figure 2

Right side: example of a patient with negative PETCT findings (a: coronal view; b: transaxial view) and CA15-3 levels of 45.3 UI/mL; left side: the same patient 6 months later with positive PETCT findings (c: coronal view; d: transaxial view) as well as CA15-3 levels of 116.8 UI/mL. Arrows indicate the metastatic sites.