Set of Genes Identifies Four Known Breast Cancer Types

A set of 50 genes can be used to reliably identify the four known types of breast cancer thus enabling oncologists to predict the most effective therapy for each tumor type and to personalize treatment for all patients.

Breast cancer results from genetic abnormalities in breast tissue, but not all breast cancers have identical genetic alterations. Matthew Ellis, MD, PhD, a member of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University (St Louis, MO, USA) and colleagues 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 investigators were able to narrow the list down to a set of 50 of these genes that could uniquely identify each type.

The tumor types were 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 also identify a fifth breast cancer type known as normal-like. The 50-gene set also recognizes the normal-like type. But the investigators 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.

"Our test is the first to incorporate a molecular profile for the basal-like type breast cancers," said Professor Ellis. "That's important because these breast cancers are arguably the most aggressive yet the most sensitive to chemotherapy. By identifying them we can ensure they are treated adequately."

In their study, the scientists also compared the activity of the 50-gene set to gauge 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 genomic test technology will be distributed through University Genomics, a company co-owned by Washington University, the University of Utah and the University of North Carolina.

The study was reported through advance online publication in the March 2009 Journal of Clinical Oncology.

Related Links:
Siteman Cancer Center at Barnes-Jewish Hospital