Serum Ferritin as a Novel Predictive Marker for Breast Cancer Metastasis and Correlation with Metastasis-Associated Burden

Background: Breast cancer became the most common cancer worldwide, Early detection of metastatic events is vital for improving survival. Currently, the serum tumor markers for monitoring metastatic breast cancer in clinic practice are carbohydrate antinegen (CA15-3) and carcinoembryonic antigen (CEA) based on the 2007 edition of American Society of Clinical Oncology (ASCO) guidelines. More specific, sensitive, and cost-effective tumor markers need to be identified to improve the accuracy of predicting distant metastasis of breast cancer. Methods: A total of 468 breast cancer patients including 170 patients with distant metastasis and 298 without metastasis were retrospectively reviewed. The levels of the serum tumor markers ferritin, CA15-3, and CEA in both the metastasis and non-metastasis groups, in subgroups of different pathologic types, different metastatic sites and different tumor burden were analyzed via One-way analysis of variance and the receiver operating characteristics (ROC) curve. compare the differences between ROC curves using paired comparison method. Results: High levels of serum ferritin predict distant metastasis of breast cancer with the highest specificity and sensitivity among all the three markers, especially in HR−/HER2+ and HR−/HER2− molecular subtypes. The prediction accuracy for metastasis increased when a combination of two or all three markers, and the combination of ferritin and CA15-3 could be the optimal choice to maximize the efficiency and predictive ability for metastasis. The baseline levels of all the three markers were associated with metastasis tumor burden and could be more sensitive in predicting patients with liver metastasis than patients with lung and bone metastases. Conclusions: the findings obtained from this study suggest that serum ferritin is a putative candidate to be a non-invasive biomarker for monitoring breast cancer metastasis which is even more sensitive and specific than the traditional breast tumor markers CA153 and CEA. However, further studies including a larger set of patient data are needed to validate the conclusions