HER-2 status predicts success of chemotherapy in breast cancer treatment

Researchers have found they can potentially target chemotherapy for breast cancer to only those women most likely to benefit, sparing the majority of patients from unnecessary side effects.

The multicenter study, led by University of Michigan Comprehensive Cancer Center researchers, found women whose breast cancer expressed a protein called HER-2 were most likely to benefit from adding the drug Taxol to the chemotherapy regimen, while women whose tumors were fueled by estrogen but did not express HER-2 did not get any benefit from the added Taxol. About 15 percent to 20 percent of breast cancers express HER-2, and as many as three-quarters of breast cancers are so-called estrogen-receptor-positive.

Results of the study appear in the Oct. 11 issue of the New England Journal of Medicine.

“In general, chemotherapy for breast cancer has been a one-size-fits-all approach. Our decision to recommend it is based on whether a woman is at high risk of the breast cancer recurring, without any idea of whether she would benefit from the additional therapy. With this data we hope we will be able to focus chemotherapy on patients whom it's most likely to help,” says lead study author Daniel Hayes, M.D., clinical director of the breast oncology program at the U-M Comprehensive Cancer Center. Hayes was the lead investigator on the study, which was run by the Cancer and Leukemia Group B through the Breast Cancer Intergroup of North America.

The study looked at tissue samples and data from 1,500 women who had previously participated in a study looking at the benefit of adding Taxol after four cycles of the drugs Adriamycin and Cytoxan, so-called AC chemotherapy. Cancer had spread to the lymph nodes in all of the women, which is a standard indication to recommend chemotherapy. All the women were given AC chemotherapy for four cycles, after which half the women received four cycles of Taxol and the other half did not receive any more chemotherapy. A previous analysis had shown that adding Taxol decreased the chances of cancer recurring and improved survival when all patients were considered, with no consideration of HER-2 status.

But, previous studies have also suggested that women whose tumors were estrogen-receptor-positive did not seem to benefit as much from chemotherapy as those women whose tumors do not need estrogen.

In this recent analysis, researchers found that the addition of Taxol improved survival rates in women who were HER-2-positive, regardless of their estrogen receptor status. But women whose tumors were HER-2-negative and estrogen-receptor-positive had no additional benefit from the Taxol. More than half of the patients in the study fell into this category.

The researchers do not recommend a change in treatment at this point, stating that more research must be done to confirm that Taxol does not benefit estrogen-receptor-positive breast cancer.

“This is the first such observation that's been made, and it was made retrospectively, meaning we looked backwards instead of forwards. We are not recommending at this time that women with positive lymph nodes, for whom we would currently recommend Taxol, but who are estrogen receptor positive and HER-2 negative not take the Taxol. We think the stakes are too high,” Hayes says.

“We've seen mortality from breast cancer dropping in recently years because we've applied these new and better therapies. But now we believe, if these results are confirmed and validated in other studies, that perhaps we could pull out half the patients in that study and save them from the toxicities and the cost of receiving a drug that might not do them any good,” he continues.

Doctors have been able to use newer drugs, such as tamoxifen, aromatase inhibitors or Herceptin, to treat only some women with breast cancer, based on whether their tumor expresses estrogen receptor or HER-2. But this method of targeting treatment had not been possible with traditional chemotherapy. This new study suggests doctors might be able to consider estrogen receptor status and HER-2 status together to determine what treatment will be most effective, sparing some women from the toxic side effects of drugs that are not likely to be effective.

“Determining who doesn't need chemotherapy and can be spared some portion of toxic therapy is one of the biggest issues facing breast cancer today,” says senior study author Donald Berry, Ph.D., professor and head of the Division of Quantitative Sciences at The University of Texas M. D. Anderson Cancer Center. “In oncology, we are very good at adding therapies to a patient's regimen, but we are not as confident subtracting treatment. Hopefully, in time, we'll be able to limit therapies to those that will truly benefit from the additional regimen.”