Our sHER2 Monitoring Algorithm
The graph below provides an optimal HERTEST® algorithm. This simple plan begins with a baseline value at the time of initial diagnosis. This strategy helps to manage therapies in HER2 positive women and uncover HER2 tumors in women with primary tumors that originally tested negative.
QUANTITATIVE SERUM HER2/NEU ELISA
CPT Code 83950
A GUIDE FOR HERTEST® MONITORING
We suggest that a woman with a positive breast cancer biopsy receive a baseline HERTEST® prior to surgical or drug intervention. Followed by:
For women with known HER2 positive tumor:
Repeat HERTEST® every two cycles during neoadjuvant and adjuvant therapy
Quarterly for three years, then annually
For women with presumed HER2 negative tumor:
Annually for three years
Upon clinical evidence of recurrence
Reference Range: 0–15.0 ng/ml (95% of women without detectable cancer)
HERTEST® values often and rapidly fall 20% or more with successful therapy.
Increased levels of HERTEST® are associated with a poor prognosis and are consistently associated with shorter time to progression and/or overall survival.
HERTEST® values may rise 3-24 months before clinical or radiological evidence of recurrence.
Simple methods to detect and follow metastatic tumors
HER2 is a cell membrane-spanning protein with functional extracellular and intracellular domains. Although HER2 is only one of several proteins capable of stimulating tumor cell growth, it is one of the few where targeted therapeutics have been developed that specifically interfere with extracellular protein interactions and intracellular cell growth signaling. Some of these drugs (HerceptinTM, for example) block interaction of the extracellular domain of HER2, thereby preventing HER2-driven cell division. Others, such as TykerbTM, enter the cell and directly inhibit the tyrosine kinase signaling pathway that triggers cell growth.
The external portion of HER2 found in serum is referred to as the extracellular domain (ECD). Enzymes in the blood cleave the ECD at the cell surface, and small amounts of ECD are present in all sera. When HER2 is overproduced, higher amounts of ECD are present. This is the rationale for HERTEST®. Many HER2 breast tumors result in serum levels above the normal range. A 20% rise from one test to the next is considered evidence of HER2 tumor growth, while effective drug therapy results in a 20% decrease in as little as three weeks. Martell now provides HERTEST® at our Minnesota-based, CLIA-certified reference laboratory.
Lung and Kidney Cancer
We are introducing a second blood test, CHECKMARK®, to measure another marker, soluble PD-L1. High blood levels indicate a poorer prognosis in patients with lung, kidney and several other cancers. But we are collaborating with clinical researchers to evaluate additional utility--can CHECKMARK® measure the effectiveness of the immunotherapy drugs called checkpoint inhibitors?
Over 100 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.
Circulating levels of HER-2/neu oncoprotein in breast cancer, Molina R, et al (2012) Clin Chem Lab Med, 50:5-21.
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.
Serum HER-2 predicts response and resistance to trastuzumab treatment in breast cancer, Petersen ER, et al (2013) Clin Chem Lab Med, 51(7):1483-92.
Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial, Witzel I, et al (2010) Breast Cancer Res Treat, 123:437-445.
Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma, Frigola X, et al (2011) Clin Can Res, 17:1915-1923.
Soluble PD-L1 as a biomarker in malignant melanoma treated with checkpoint blockade, Zhou J, et al (2017) Cancer Immunol Res, 5(6):480-492.