Investigators say that they have narrowed down 50 genes that play a role in identifying the four subtypes of breast cancer. By measuring the expression level of these genes in the tumors, they were also able to determine how each individual will respond to chemotherapy.
Besides these four tumor types—luminal A, luminal B, HER2-enriched, and basal-like—a fifth breast cancer type known as normal-like has also been identified. According to the current research, the team says that the normal-like classification is really an indicator that a sample contains insufficient tumor cells to make a molecular diagnosis and that a new sample needs to be taken.
The scientists analyzed the gene activity of more than 1,000 breast tumors to identify and validate the genetic signature of each of the four types of breast cancer. Although the cancer types are distinguished by thousands of genetic differences, the researchers were able to pinpoint 50 genes that could identify each type.
The researchers also compared the activity of the 50-gene set to how well 133 breast cancer patients responded to standard chemotherapy. They found that their genetic test was highly sensitive and very predictive for chemotherapy response. The test was more predictive than typically used clinical molecular markers such as estrogen receptor status, progesterone receptor status, or HER2 gene expression status.
Luminal A was not sensitive to the chemotherapy, suggesting that patients with this good-prognosis type can forgo chemotherapy in favor of hormone-based therapy. Among poor-prognosis tumor types, basal-like breast cancer was the most sensitive to the chemotherapy and luminal B the least.
The group is currently designing prospective clinical trials using the test, which they call the Breast Bioclassifier. The researchers will investigate how each tumor type responds to the more than 20 drugs available to treat breast cancer.
The genomic test technology is patented and will be distributed through University Genomics, a company co-owned by Washington University, the University of Utah, and the University of North Carolina. University Genomics is working with Associated Regional and University Pathologists, a reference laboratory at the University of Utah, to provide a site where the 50-gene test will be available by this summer.
The study appeared February 9 in the advance online publication of the Journal of Clinical Oncology.
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