Drug helps against certain breast cancers

In nearly one-third of breast cancer cases, a gene encoding a protein called HER2 runs amok. The resulting oversupply of HER2 makes the cancer more aggressive and prone to spread.

Scientists created a stir in 1998 when they reported preliminary findings that the drug trastuzumab, a bioengineered antibody, could prolong survival in some breast cancer patients by neutralizing excess HER2. Details of that study, now published in the March 15 New England Journal of Medicine, have rekindled the optimism sparked by the earlier report.

The drug–called Herceptin by its maker, Genentech in South San Francisco, Calif.–quells HER2 by binding to it. Physician Dennis J. Slamon of the University of California, Los Angeles School of Medicine and his colleagues targeted HER2 because it’s suspected of contributing to cell proliferation.

In 1995, the scientists randomly assigned 235 of 469 women with aggressive breast cancer to get standard chemotherapy drugs plus trastuzumab for several months. The length of the regimen depended on a patient’s progress. Meanwhile, the other 234 women in the study received chemotherapy alone.

All the women’s breast cancers had spread to their lymph nodes and at least one other organ. That’s an ominous development that leaves a patient with an average survival time of less than 2 years, despite current treatments, says Peter M. Ravdin of the University of Texas Health Science Center in San Antonio.

During the trial, 8 percent of the patients getting trastuzumab showed a complete response–all tumors disappeared at some point–and 43 percent showed partial improvement, meaning tumors shrank by more than half. Of patients getting just chemotherapy, only 3 percent responded completely and 28 percent had a partial improvement.

Patients stayed on therapies unless their disease worsened, at which time they were given a choice of other treatments, including trastuzumab if they weren’t getting it already. Patients who started the trial on trastuzumab lived an average of 25 months from the start of treatment, compared with 20 months for women who didn’t receive the drug or who only got it belatedly.

“This [study] is the first of what will be a very exciting new arena” of research, says oncologist Julie R. Gralow of the University of Washington in Seattle. Gralow notes that trastuzumab is the first therapy of its kind for breast cancer. It’s a monoclonal antibody, meaning it attacks a specific molecular target–in this case the HER2 protein. Unlike most chemotherapy drugs, Gralow says, “it targets what is unique about a tumor.”

On the basis of preliminary findings of this study, the Food and Drug Administration approved trastuzumab for treating patients with advanced breast cancer.

The drug does have side effects. Of the women receiving it with chemotherapy, 40 suffered heart failure, compared with only 9 of those getting chemotherapy alone. One in each of these groups died from the side effect. Two new trials of the drug will include regular heart tests for patients, including women whose cancer is confined to the breast and lymph nodes.