Evidence-based Genetic Testing | Breast Cancer July 20, 2007Posted by ramunas in breast cancer, cancer genetics, genetic testing, MammaPrint, Oncotype DX, sporadic cancer.
On 18th of July, Blue Cross and Blue Shield Association, the Technology Evaluation Center (TEC), which is assessing medical technologies through objective, scientific evidence-based, comprehensive reviews of clinical evidence, has announced final decision on several genetic oncological tests.
The Medical Advisory Panel (MAP) concluded that:
The use of Oncotype DX™ to inform decision making about adjuvant chemotherapy meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria for women with estrogen receptor-positive, node-negative, tamoxifen-treated breast cancer;
- all other uses of Oncotype DX™ do not meet TEC criteria;
- use of MammaPrint® gene expression profiling does not meet the TEC criteria;
- use of the Breast Cancer Gene Expression Ratio gene expression profiling does not meet the TEC criteria.
- use of epidermal growth factor receptor (EGFR) mutation analysis to predict therapeutic sensitivity to erlotinib (Tarceva®) therapy (for non-small cell lung and pancreatic cancer) does not meet the TEC criteria. (via)
TEC five criteria are used to assess whether a technology improves health outcomes such as length of life, quality of life and functional ability.
On February a Dutch company Agendia’s DNA micro array-based in vitro diagnostic laboratory service MammaPrint® was approved by FDA for marketing in the U.S.. It determines the likelihood of breast cancer returning and metastasis within five to 10 years after a woman’s initial cancer. That was the first cleared molecular genetic expression test, already used in Europe from 2005. MammaPrint measures the expression (activity) of 70 genes that predict the chances of a relapse. Customized microarrays, manufactured by Agilent, are used. There is a nice open-access article on BMC Genomics describing its development and several covering articles on PubMed. Acctually, MammaPrint is commercialized version of a very known and depicted in most cancer genetics textbooks gene expression study by van’t Veer et al (2002).
However MammaPrint did not fit into TEC criteria. Could that because of a small sample size (clinical data from 302 patients)? We need to wait more for evidence data to accumulate and be sure for the relevance of this test.
Breast Cancer Gene Expression Ratio gene expression profiling, an approach developed by Massachusetts General Hospital (MGH) Cancer Center and Arcturus Bioscience, Inc., which is based on the ratio between the expression levels of two genes – HOXB13 and IL17BR, predicts the likelihood for a tumor to recur. The higher the expression level of HOXB13 and the lower the expression of IL17BR, the greater the chance of tumor recurrence (via). Unfortunately, this methodology also did not meet TEC criteria.
The same failure is for (EGFR) mutation analysis to predict response to tyrosine kinase inhibitors (TKI), like erlotinib, cause there are some data, that non-small cell lung and pancreatic cancer patients with a 15 bp exon 19 deletion could have a swift response on erlotinib (via).
Only Oncotype DX, a diagnostic multi-gene expression test from California based GenomicHealth company, that provides the likelihood of distant breast cancer recurrence in women with newly diagnosed, early stage invasive breast cancer and assesses the benefit from chemotherapy, has met quite strict TEC criteria. The assay is performed using formalin-fixed, paraffin-embedded (FFPE) tumor tissue and analyzes the expression of a panel of 21 genes using quantitative TaqMan® RT-PCR reactions in 384-well plates and the results are provided as a Recurrence Score™ (0-100) (via). They have done quite a lot of work on optimization and selection from 250 canditates genes (via).