Breast Cancer DNA Study Yields New Targets for Therapy

Genetic mapping of hundreds of breast cancer tumors confirmed there are four main subtypes and discovered that one closely resembles ovarian cancer, suggesting the two may be attacked with similar therapies.

The study, in which the genomes of 825 breast tumors were sequenced, was the most comprehensive of its type involving the disease. It is part of a U.S. research project into the genetics of 20 types of cancers. Earlier this month, the group, called the Cancer Genome Atlas project, released a similar report on new DNA mutations affecting a type of lung malignancy.

The breast cancer findings were published yesterday in the journal Nature. They support the expanding medical view that cancers should be categorized by their genetic origins, rather than where they’re found on the body. The link between breast and ovarian cancer gives scientists added leverage to compare treatments and outcomes across both tumors.

“There are certain mutations you can find across cancers in different organs,” said Eric Topol, a professor at the Scripps Research Institute in La Jolla, California, who wasn’t involved in the research. “This is a real transition point, and we have to move toward more sequencing to give patients the best shot toward curing their cancer.”

The personalized medicine approach has fueled a move among drugmakers to identify treatments targeting genetic mutations, such as Roche Holding AG’s Zelboraf and Pfizer Inc.’s Xalkori.

Drug Targets

For years, doctors have classified breast cancers according to measures such as how they invade other tissues, their cellular variability, and their appearance when stained with certain chemicals, said Paul Billings, a geneticist who is medical director Life Technologies Corp., a maker of DNA sequencers in Carlsbad, California.

“That’s the old world,” Billings said. “The new world is a diagnostic system that will be based on targetable DNA mutations present in breast cancer.”

In the breast cancer study, a computer analysis suggests the form known as “basal-like,” named for its resemblance to basel skin cells, may be treatable with drugs that either cut off the tumor’s blood supply, prevent blood vessel growth or chemotherapy, according to a statement from the National Cancer Institute.

The research released yesterday backed up earlier work segmenting breast cancer into four groups according to genetic markers: HER2-enriched, Luminal A, Luminal B and basal-like.

72 Therapies

More than 72 gene-based therapies are available already, a fivefold increase from the 13 available in 2006, according to the Personalized Medicine Coalition, an industry advocacy group based in Washington.

Among these drugs are Zelboraf, from Basel, Switzerland-based Roche, the world’s biggest maker of cancer drugs, and Xalkori, from New York-based Pfizer, approved to treat a rare form of lung cancer.

“With this study, we’re one giant step closer to understanding the genetic origins of the four major subtypes of breast cancer,” Matthew Ellis, a lead author of the study and oncology professor at Washington University School of Medicine in St. Louis, said in a statement. “Now, we can investigate which drugs work best for patients based on the genetic profiles of their tumors.”

Therapies already exist that target some of these genetic markers. Roche’s Herceptin is aimed at patients whose tumors have the HER2 abnormality. An estimated 226,870 women will be diagnosed with breast cancer this year, and 39,510 women will die from the disease, according to the National Cancer Institute.

The breast cancer study, funded by the National Cancer Institute and the National Human Genome Research Institute, is the fifth report released by the Cancer Genome Atlas project.

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