Doctors have long known that many early-stage breast cancer patients who get chemotherapy don't actually need it to prevent recurrence of the disease after surgery. But they haven't known exactly which patients might safely skip the toxic treatment.

A European study published Wednesday in the New England Journal of Medicine sheds new light on the issue, concluding that many such patients might be able to avoid chemo.

The key factor: Nearly half of the patients considered at high risk for recurrence might actually be low risk based on genetic factors, researchers found.

The study involved almost 6,700 patients with localized breast cancer that hadn't spread beyond three lymph nodes. Of those, about half were considered high risk based on clinical measures such as tumor size and patient age. Typically, all would have received chemotherapy as part of their treatment.

But a 70-gene test called the MammaPrint test found that about 1,500 of that group were low risk based on genomic factors. They were considered "discordant" -- high-risk patients based on clinical factors, but low risk based on gene-test results.

The 1,500 women then were put randomly into two groups, with one getting chemo and one not getting it. After five years, the survival rates of the groups were similar -- just 1.5 percentage points higher for the women who'd received chemo. The survival rate for the non-chemo group was close to 95 percent.

Given those findings, the researchers say, about 46 percent of women with breast cancer who are classified as high risk based on clinical factors might not need chemo.

Study co-author Laura van 't Veer, a molecular biologist and leader of the breast oncology program at the Helen Diller Family Comprehensive Cancer Center at the University of California at San Francisco, did the research that led to the gene test while working for the Netherlands Cancer Institute.

Van 't Veer, who is an officer in the company now marketing the test, said MammaPrint "looks under the hood of the tumor and into the engine of the cancer to show whether the biology is truly aggressive and has capacity to invade surrounding issue."

She said the 1.5 percentage-point difference in survival rates between women who got chemo and the ones who didn't was not statistically significant, especially considering the side effects of chemo, which can include fatigue, cognitive impairment and a prolonged disruption in schedule.

But Paul Kelly Marcom, a breast cancer oncologist at Duke Cancer Institute, said that whether that survival-rate difference is significant is a personal decision by a woman and her doctor.

He also noted that there are other genomic tests on the market and that physicians are in the early stages of learning how to use them. "It's not a quick or easy process," he said, adding that he thinks physicians need more data before making big changes in clinical practice.

Another test, called Oncotype DX, came on the U.S. market earlier and is more widely used. But it analyzes a smaller set of genes than MammaPrint and is used for only certain types of breast cancer.

Both Oncotype DX and MammaPrint cost about $4,000. In many cases, Marcom said, insurance covers the tests.

An accompanying editorial said the trial showed "how a well-coordinated and highly collaborative multinational team of investigators can efficiently conduct a potentially practice-changing study."

It said the results "could allow some doctors and patients to choose to avoid chemotherapy if they have carefully considered their own tolerance for toxicity, risk, and uncertainty." Yet such decisions are "highly individualized."

The European study was called MINDACT for Microarray for Node-Negative Disease May Avoid Chemotherapy Trial. Some of the information was released in April at the American Association for Cancer Research annual conference.