Serum HER2 levels above 1000 ng/mL was an indicator that standard doses of Trastuzumab may be insufficient as reflected by low concentrations of serum Trastuzumab.53 Several studies now support the observation that a significant decrease in sHER2 levels from baseline to 30�C90 days after initiation of treatment is a predictor selleck kinase inhibitor of outcome to HER2-targeted therapies. In contrast, patients with increasing sHER2 levels, a persistently high sHER2 level or who do not achieve at least a 20% decline in sHER2 levels in the early weeks and months of HER2 targeted therapies may benefit from treatment with new HER2 inhibitors that are in clinical development.52,54 Since patients can have increases in sHER2 levels that occur earlier than actual clinical signs of recurrence, routine monitoring of sHER2 levels can be an early warning sign for physicians and patients to consider additive or alternative therapy strategies.

Earlier detection of cancer progression is an actionable event for the oncologist and one which can trigger intervention with the variety of therapies or combination of therapies that are now available for breast cancer patients. In theory, the sooner one attacks a tumor, particularly while the tumor burden is low, the better the probability of a positive patient outcome. Well-defined clinical studies are needed to test this hypothesis. Studies conducted thus far have collectively shown that patients treated with hormone therapy, chemotherapy, Trastuzumab, Lapatinib, or a combination of these therapies have serial changes in sHER2 levels that paralleled changes in the clinical course of disease; therefore, patients with HER2-positive breast cancer can greatly benefit from routine monitoring of thes HER2 level.

14�C17,21,22,25,52,54 Controversy Surrounding Serum HER2 Testing in all Breast Cancer Patients as a Prognostic Biomarker In contrast to the large number of publications that illustrate the clinical value of sHER2 testing, a handful of publications have reached negative conclusions regarding the clinical value of measuring this specific circulating biomarker for HER2-positive breast cancer. Articles by Lennon et al55 Leary et al56 and Leyland-Jones et al57 are the most notable. All three publications agreed with the 2007 ASCO guidelines and did not recommend sHER2 testing for clinical use.

The articles by Leary et al and Leyland-Jones et al primarily reviewed publications that used research use only assays that were not standardized or validated by acceptable diagnostic protocols and procedures. In general, the research use only assays listed in the data tables of these publications did not define the specificity of the capture and detection antibodies in the assay nor was there a definition of what constitutes a statistically significant change between 2 serial blood Anacetrapib samples.