We are promoting routine monitoring of the serum HER2 biomarker in women with metastatic breast cancer. The usefulness of circulating biomarkers in breast cancer management has been studied and debated for years. Most of the attention has focused on CA 15-3 and CA 27.29, which are products of the MUC-1 gene. Serum HER2 is not mentioned in the NCCN guidelines, a preeminent resource for breast cancer management. A review of breast cancer biomarkers published by an ASCO committee in 2007 raised questions about the sHER2/neu test. Those concerns have been resolved by multiple investigators over the intervening years. More recently, mongraphs and recommendations from an expert AACC panel seem to support serum HER2 monitoring. The consensus of evidence indicates strong prognostic (disease free survival) and predictive (response to therapy) value.
Serum HER2 tests may be elevated at the time of initial Stage 2-4 diagnosis. But an elevated sHER2/neu value in the presence of a questionable tissue test may indicate a HER2 tumor missed by tissue testing. Months or even years later, a tumor originally classified as HER2 negative may give rise to HER2 metastases, and elevated sHER2/neu may be the first clue. Elevated serum HER2, at the time of biopsy or later, carries a poorer prognosis, but the prognosis improves considerably with effective HER2-targeted therapy.
An elevated serum HER2 falls quickly with effective treatment, often within three weeks. A 20% decline is considered a sign of effective treatment, whereas a 20% increase indicates treatment failure.
During routine sHER2/neu monitoring of women with metastatic breast cancer, an elevated value may appear and continue to rise for months before clinical symptoms or radiologic evidence of recurrence. Since physicians treat only upon clinical or radiologic evidence, serologic evidence may be considered problematic. However, we believe that detection of a continuously rising sHER2/neu serum level will improve monitoring and lead to earlier and more effective targeted therapy in this subset of patients.