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Combination treatment stymies breast cancer growth

A combination of three different drugs that block the HER-2 receptor, a critical cellular growth signal for some breast cancers, eradicated aggressive breast tumors in mice and could point the way toward developing better treatments inpatients, said researchers from the Breast Center at Baylor College of Medicine in a report that appears today in the Journal of the National Cancer Institute.

"For the first time, we were able to cure mice of a very aggressive human breast tumor," said Dr. Rachel Schiff, assistant professor in the Breast Center at Baylor College of Medicine and senior author of the report.

In prior such studies, treatment only slowed or delayed the growth of tumors, she said. In this case, the tumors disappear and do not come back, even when treatment is stopped.

The treatment involved is a new approach known as "targeted" therapy because the protein (in this case, HER-2) driving a tumor to grow is first identified in a patient's tumor and then specific drugs are used to block that particular growth pathway in the cells, said Dr. Kent Osborne director of the Breast Center and the Dan L. Duncan Cancer Center with BCM. He is also an investigator on the study.

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"When you go after a specific target in a patient's tumor, the treatment is likely to be more effective and less toxic," said Schiff.

The tumors in question – nearly 25 percent of all breast cancers – have high levels of HER-2. While the HER-2 makes the tumors more aggressive, it also provides a target against which new drugs can act.

Previously, treatment for patients with HER-2 positive tumors was less effective.

"Now we have effective treatment, and survival is markedly improved," said Dr. Grazia Arpino, lead investigator of the study and a postdoctoral fellow at BCM.

"These tumors are initially highly sensitive to a drug known as trastuzumab or Herceptin, one of the drugs used in combination in the mouse study and which is approved by the FDA (U.S. Food and Drug Administration) for treatment," said Schiff.

However, the tumor is wily and can sometimes escape the drug's effects, resulting in resistance. Adding two other experimental drugs – gefitinib and pertuzumab -- that inhibit HER-2 in different ways can more completely block the growth signals in the tumor, causing it to die.

In one of the tumors studied in this report, blocking the stimulatory effects of estrogen on the tumor was also necessary for optimal treatment, said Schiff. Completely blocking the HER pathway is critical, she said. Leaving out just one of the three drugs was much less effective.

A clinical study using drug combinations in newly diagnosed patients with HER-2 positive breast cancer will start soon under the direction of physicians at BCM's Breast Center, said Osborne.

"We are very excited to see if our laboratory results can be translated to patients with the more aggressive types of breast cancer," he said.

Kimberlee Barbour | EurekAlert!
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