BCRF Researcher Plays Key Role in New Genomic Test for Breast Cancer

Fifty-Gene Test Personalizes and Improves Treatment

In February, BCRF researcher Charles Perou, PhD, of the University of North Carolina-Chapel Hill, saw more than a decade's worth of scientific work come to fruition. A 50-gene molecular profile of breast cancer that he began working on as a postdoctoral fellow at Stanford University in 1997 has now become a viable screening test that can be used by clinicians to identify the four known "intrinsic subtypes" of breast cancer. "This new genomic test is a collaboration among four investigators and four institutions," says Perou. "It is also the culmination of about 10 years worth of work."

Breast cancer is a result of genetic abnormalities in breast tissue, but not all breast cancers have identical genetic alterations. Perou, along with his colleagues Matthew Ellis, MD, PhD, of Washington University, St. Louis (also a BCRF grantee), Torsten Neilsen, MD, PhD, of The University of British Columbia, and Philip S. Bernard, MD, of the University of Utah, analyzed the gene activity of more than 1000 breast tumors. They found that they could reliably separate the genetic signatures of these tumors into four groups that correspond to the four known subtypes of breast cancer: luminal A, luminal B, HER2-enriched and basal-like. The new, 50-gene test also recognizes normal-like tissue, which is an indicator that a new sample needs to be taken to make a more accurate molecular diagnosis. Prior to this, the sole genomic test that is widely accepted applied only to lymph-node negative, estrogen-receptor positive breast cancer. The new genomic test developed by Perou, Ellis, Neilsen and Bernard is broadly applicable for all women diagnosed with breast cancer.

The new test helps cancer doctors in several ways. By identifying all the known breast cancer subtypes, it helps doctors treat them adequately. Before this test, for example, there was no molecular profiling tool for basal-like breast cancers, which are highly aggressive, but sensitive to chemotherapy. By knowing that they are dealing with a basal-like type, doctors can more confidently proceed with chemotherapy as an effective treatment for patients with this subtype.

In this study, Perou and his colleagues compared the activity of the 50-gene set to how well a group of patients responded to chemotherapy. They found that their test was highly sensitive and predictive for chemotherapy response. Luminal A tumors were not sensitive to chemotherapy, for example. This finding suggests that patients with this type of breast cancer may forego chemotherapy in favor of hormone-based therapy. After Luminal A tumors, Luminal B cancers were also not very responsive to chemotherapy. Because luminal B cancers are a very poor prognosis group, and none of the conventional therapies are particularly effective against it, the ability to identify luminal B tumors makes it possible to home in on it and develop better therapies for it.

With more than 20 drugs available to treat breast cancer, the team is now investigating how each tumor type responds to these drugs in order to determine the best treatment for each, a step forward in personalized medicine.

The genomic test technology will be distributed through University Genomics, a company co-owned by the University of North Carolina, Washington University and the University of Utah. University Genomics is working on establishing a reference laboratory site where the 50-gene test will be supported.