Serum human epidermal growth factor 2 extracellular domain as a predictive biomarker for lapatinib treatment efficacy in patients with advanced breast cancer, Lee CK, et al (2016) J Clin Oncol, 34(9):936-944. This paper found serum HER2 to be a more reliable indicator of lapatinib efficacy than tissue testing.

Serum HER-2 predicts response and resistance to trastazumab treatment in breast cancer. Peterson ERB, Sorensen, PD, Jacobsen, EH, Madsen, JS and Brandslund, I, Clin Chem Lab Med (2013) 47:1117-1123These authors describe decreasing sHER2/neu values greater than 20% during successful Herceptin treatment and rising values in progressive disease.When comparing women judged to be free of disease to women alive with recurrence, there was a dramatic shift in median sHER2/neu values.

Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial. Witzel I, Loibl S, von Minckwitz G, Mundhenke C, Huober J, Hanusch C, Henschen S, Hauschild M, Lantzsch T, Tesch H, Latos K, Just M, Hilfrich J, Barinoff J, zu Eulenburg C, Roller M, Untch M, Muller V, Breast Cancer Res Treat (2010) 123:437-445. This paper, summarizes data from a large German trial involving 175 patients. The authors looked at sHER2/neu during neo-adjuvant treatment, when chemotherapy is given before surgery to reduce tumor size and spare breast tissue at surgical removal. Monitoring sHER2/neu was helpful in predicting clinical response. This paper discusses an as yet unresolved issue—some sHER2/neu values in the range of “normal”, maybe as many as half, may still indicate the presence of a HER2 tumor and merit monitoring during treatment. ​

Human epidermal growth factor 2 (HER2) extracelluar domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving laptinib monotherapy. Lipton A, Leitzel K, Ali SM, Carney W, Platek G, Steplewski K, West P, Lund R, Gagnon R, Martin A, Maltzman J, (2011) Cancer. The most reliable way to evaluate the utility of a sHER2/neu test during treatment is to study women treated with only one HER2-targeted drug. This article evaluated patients receiving only the HER2-targeted drug lapatinib. They observed a greater than 20% fall in sHER2/neu, often as early as four weeks, in patients responding clinically. These doctors, as have others, published very similar results with single drug trastuzumab treatment in a 2008 report. As the number of HER2-targeted drugs increases and the cost of treatment increases, a tool to detect early evidence of drug failure takes on new meaning.​​​

Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma, Frigola X, Inman BA, Lohse CM, Krco CJ, Cheville JC, Thompson RH, Leibovich B, Blute ML, Dong H, Kwon ED, (2011) Clin Can Res, 17:1915-1923.A careful evaluation of soluble PD-L1 in Mayo Clinic patients.

Soluble programmed cell death ligand 1 as a novel biomarker for nivolumab therapy for non-small-cell lung cancer, Okuma Y, Waku H, Utsumi H, Sagawa Y, Hosomi Y, Kuwano K, Homma S (2018) Clin Lung Cancer, 19:410-417, 2018.32 patients with non-small-cell lung cancer had elevated serum PD-L1 levels. Those with very high values were most frequently unresponsive to immunotherapy.

Here are a few references and comments:

Over100 articles supporting serum HER2 (sHER2/neu) monitoring have been published during the past ten years. These articles have been written by teams of clinical researchers either reviewing medical records or conducting prospective studies structured to follow women during and after treatment. Most articles support sHER2/neu testing of women with metastatic breast cancer, repeating the test during treatment and periodically thereafter to detect any failure in treatment or progression. Several recent articles support the prognostic value of soluble PD-L1 as a serum biomarker.