Uses and abuses of tumor markers in the diagnosis, monitoring, and treatment of primary and metastatic breast cancer.

Although breast cancer incidence continues to increase, mortality has been decreasing, principally as a result of earlier detection and improvements in adjuvant systemic therapy. Nonetheless, because antineo-plastic agents are associated with substantial morbidity and occasional mortality, efforts to individualize treatment strategies are desirable. In addition to classic histopathologic diagnosis, molecular and cellular tumor markers may help in establishing prognosis or prediction of benefit. Recommendations for routine use of tumor markers in breast cancer have been conservative. Although several studies have been reported, few are of sufficiently high level of evidence to permit solid conclusions. Three key issues in tumor marker evaluation are utility, magnitude, and reliability. Poorly conceived study designs cloud the issue of how the marker might be used. Reliance on p-values rather than the size of the differences in outcome between patients who are positive and those who are negative for the factor obscures the importance. Technical issues result in poor reproducibility and interpretability of assays. Analytical issues lead to poorly defined cutoff values for marker levels. Poor patient selection leads to difficulty interpreting results because of confounders such as differences in treatment regimens. This review focuses on these issues, with an emphasis on currently accepted tumor markers. Finally, new tumor marker reporting recommendations are discussed, the adoption of which may lead to improved design and publication of tumor marker studies in the future.