We found functional circulating Her-2-reactive T cells in 97% of the patients, almost all of whom possessed antigen-reactive CD4+ T cells.
This observation suggests that circulating HER-2/neu level not only is a marker of tumor over-expression but also is indicative of the degree of receptor activation.
Aliquots of the same serum samples were previously used to measure changes in serum troponin levels and in circulating HER-2 receptor domain during preoperative therapy (Buzdar et al, 2005; Mazouni et al, 2007).
However, trastuzumab elimination seems to depend on high serum levels of circulating HER-2 extracellular domains, which can be cleaved from the surfaces of cancer cells by matrix metalloproteinase and released into the serum.
In a 1999 report [ 26], using the same enzyme-linked immunosorbent assay based on mAb 4D5, baseline serum concentrations of the circulating HER-2/neu were below the detectable concentration in 73 out of 191 patients (38%).
Before the decision by the FDA to clear the serum HER-2/neu test with a standardized cutpoint of 15 ng/ml, many reports used different research assays with various, uncharacterized antibody specificities, calibrators, and cutoff values to measure circulating HER-2/neu level.
Recently, there has been an increasing interest in detecting the circulating HER-2 protein in serum samples for use as a complementary assay to IHC and FISH analysis for diagnosis, but also for use as a prognostic marker for breast cancer recurrence [ 46, 47].
In a study published in 1998 [ 25], using a homebrew HER-2/neu assay and mAb 4D5 as the capture reagent, it was reported that 259 out of 443 (58%) patient sera did not have measurable circulating HER-2/neu levels.
As she circulated her proposal, she said, "even council members are saying that they use it to their wives".
