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Genetic Variations Identify Breast Cancer Types

Oncologists now know where to look in the genome to identify breast cancer, according to a study reported in the Journal of Clinical Oncology. Using a set of just 50 genes, they can reliably identify the four known types of breast cancer and potentially predict the best therapy for each tumor type.

Although the cancer types are distinguished by thousands of genetic differences, the researchers were able to narrow the field down to a set of 50 genes that could uniquely identify each type. These tumor types have been previously defined and are known as luminal A, luminal B, HER2-enriched and basal-like. The latter three types are generally considered types with a poor prognosis. Another genomic test commonly used in clinical practice, OncotypeDX, does not identify all four tumor types.

Breast cancer experts typically also identify a fifth breast cancer type known as normal-like. The 50-gene set also recognizes the normal-like type. But the researchers found that instead of being a fifth type of breast cancer, the normal-like classification is an indicator that a sample contains insufficient tumor cells to make a molecular diagnosis and that a new sample needs to be taken.

In this study, Matthew J. Ellis, MD, PhD, a medical oncologist at Washington University and the Siteman Cancer Center, and physicians from collaborating institutions were looking to develop a risk model that incorporates the gene expression–based “intrinsic” subtypes. 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.

The researchers plan to study tumor samples from breast cancer cases going back a decade or more. Since the patients in these cases have already been treated, the researchers can relatively quickly discover how well various therapies worked for each breast cancer type.

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.
Parker, JS, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. Journal of Clinical Oncology. 27, 1160-1167 (2009).
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