March 26 (Bloomberg) -- Genentech Inc.'s Herceptin, a drug for breast cancer patients who have a gene mutation, appeared to help women lower their risk of relapse even if they don't have the variation, researchers said.

A trial of 1,787 women with early stage breast cancer was a success because it showed Herceptin lowered the risk of relapse. On further analysis, researchers made a surprising finding. About 10.6 percent of patients with the HER2 gene mutation, which the drug blocks, had tumors spread. About 8.5 percent of women with a normal form of the gene, who aren't supposed to benefit, showed a worsening of their disease, according to research in this week's New England Journal of Medicine.

Herceptin, first approved in 1998, is designed to work by blocking excess HER2 proteins that amplify tumor growth. More recent studies have shown it can reduce the risk of relapse for women with an early stage of disease. The trial wasn't meant to show the drug can help women with normal HER2 genes, and it shouldn't be used to justify giving those women the drug until more evidence is gathered, researchers said.

``The results are intriguing,'' said Anne Blackwood- Chirchir, Genentech's group medical director, in a telephone interview. ``The number of patients are small, and whenever we work with small numbers, we need to question it a bit.''

Still, it may prompt another clinical trial to explore whether the drug can be used more widely. The benefits of the drug ``may not be limited to patients with HER2 amplification,'' said Soonmyung Paik, a researcher with the National Surgical Adjuvant Breast and Bowel Project, in a letter to the editor in the New England Journal.

About 182,000 women in the U.S. will be diagnosed with breast cancer this year, according to the Atlanta-based American Cancer Society. About one-fourth have the HER2 gene mutation.

Herceptin generated $1.29 billion in U.S. sales in 2007, according to Genentech. It's the company's third-biggest product behind Avastin and Rituxan.

The trial was intended to enroll only patients who test positive for a HER2 gene mutation at their hospital, although about 10 percent were found to have more normal tumor types upon further review by an expert pathologist, Blackwood-Chirchir said.

The study found that 86 of 804 women, or 10.6 percent, with the mutation had tumors spread after taking Herceptin and chemotherapy. That compares with 7 of 82, or 8.5 percent, of women with the normal HER2 genes whose disease worsened after getting Herceptin, researchers said. Other women in the trial, who took chemotherapy alone, had higher rates of relapse.

More work needs to be done to confirm that Herceptin helped women with the normal genetic profile, Blackwood-Chirchir said. Results of the analysis, expected by the end of the year, could lead to a larger clinical trial to answer whether Herceptin can benefit more women.

`Gray Zone' of Women

It's possible Herceptin may be working because there is a ``gray zone'' of women whose HER2 genes are amplified in part of the tumor, not throughout, so they aren't detected in tumor samples. Another idea is that women with early disease have small tumors, called micrometastases, and Herceptin may recruit the immune system to kill tumors, instead of blocking excess HER2 proteins, she said.

Genentech, based in South San Francisco, rose $1.64, or 2 percent, to $82.01 at 4 p.m. in New York Stock Exchange composite trading. The stock fell 1.3 percent in the last year.

Genentech's Avastin, which cuts blood flow to tumors, was approved for marketing by the U.S. Food and Drug Administration in February for women who lack the HER2 mutation.

To contact the reporter on this story: Luke Timmerman in San Francisco at ltimmerman@bloomberg.net

Last Updated: March 26, 2008 17:00 EDT