Hope in Herceptin

Seattle Cancer Care Alliance oncologists find breast-cancer drug helps block deadly overexpression of cell-regulation protein
patient Joy Tseng and SCCA nurse Heather Bybee
Joy Tseng (left), a patient from Montana, chats with SCCA nurse Heather Bybee while receiving Herceptin. The breast-cancer drug helps control production of a protein involved in the regulation of cell growth. Photo by Dean Forbes

When the breast-cancer drug Herceptin hit the market in 1998, federal health officials welcomed it as a turning point in the fight against one of the deadlier forms of the illness. Today, researchers, including doctors at the Seattle Cancer Care Alliance (SCCA), are still working to understand Herceptin, the results it has produced and how it can best benefit future breast-cancer patients.

As with most cancer drugs, Herceptin was first used to treat late stages of breast cancer, but now there is research showing the drug's impact on earlier stages of the disease.

Herceptin helps control the production of HER2, or human-epidermal growth factor receptor 2, which is a protein found on the surface of every healthy breast cell. When all goes normally, the protein helps to regulate cell growth. But if the cell has too many copies of the HER2 gene, too much protein is produced, or overexpressed. Researchers believe the overexpression of the protein may turn a healthy cell into a cancerous one.

For years, a HER2 positive diagnosis was devastating news. "We've seen that patients who overexpress this certain protein do worse. They die faster, they metastasize earlier, and they have higher mortality rates," said Heather Bybee, a registered nurse who helps coordinate clinical trials for breast-cancer patients at the SCCA. But since Herceptin was introduced, Bybee said, a HER2-positive diagnosis isn't such bad news for patients, as Herceptin actually blocks the overexpression of HER2.

SCCA doctors agree that the drug is helping take important steps toward winning the breast-cancer battle. "For a tumor type that used to be very dangerous, this is actually a relatively positive diagnosis," said Dr. Julie Gralow, an oncologist. One of the unique qualities of Herceptin is that it targets the specific genetic defect that allows overexpression of HER2, which occurs in about 20 percent to 25 percent of breast-cancer patients. "Herceptin has made a dramatic difference in that subpopulation of patients," Gralow said. In early analyses of four large randomized adjuvant Herceptin trials, breast-cancer recurrence rates dropped by an average of 50 percent.

Less toxic treatment

Another advantage is the lack of side effects for Herceptin patients. "It's not a chemotherapy, so it doesn't have the same toxicity profile, meaning nausea and vomiting," Bybee said. "You don't get the irritation of all the fast-growing cells in your body, so you don't lose your hair, your fingernails aren't affected, things like that."

Patients do face a slight risk of heart problems when using the drug, but providers say they monitor closely for any indication of complications, and the potential for problems is very small. "In terms of toxicity, it seems to be a better tolerated drug overall," said Dr. Georgiana Ellis, an SCCA oncologist.

Herceptin is taken intravenously once a week or once every three weeks. It takes about half an hour to complete the treatment, and patients are well enough to leave the clinic immediately afterward. Ellis said that this treatment could be used in more locations. "All you have to watch out for are allergic reactions, and the risk of those is pretty low. I think family practitioners and general internists ought to be able to give this, and it shouldn't need to be confined to oncology offices."

Currently, patients take Herceptin for one year, but that might change soon, Ellis said. A recent study suggested that the drug is nearly as effective in a nine-week timeframe as in a yearlong trial.

"If you don't need a full year, it's certainly cheaper, and there's a lower chance of heart failure," Gralow said.

But the work is far from finished, Ellis said. "Researchers are still working to fine-tune treatment to give patients maximum benefit. The drug is still so new that it's hard to really gauge just what an impact it will have in the long run," she said.

Despite the positive early results and the enthusiastic reception by patients, it will likely be awhile before the capabilities of Herceptin are fully understood. In adjuvant studies, the relapse rate has been cut and mortality rates have been falling overall, but most people are cautiously watching the results. "I think what we're hoping for in our heart of hearts is a true breakthrough drug that will cure the problem, but we haven't gotten to that by adding this drug," Ellis said.

While Herceptin may just be one step toward progress, it's unknown how far that step will stretch in the big picture. "We'll have to see five years from now whether this is a bigger than usual small step that's been made by the addition of this drug," she said. "This could prove quite substantial, but we'd still like to see every last case eradicated."

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