When is it safe for a woman with breast cancer to skip chemotherapy?
A new study helps answer that question, based on a test of gene activity in tumors. It found that nearly half of women with early-stage breast cancer who would traditionally receive chemo can avoid it, with little risk of the cancer coming back or spreading in the next five years.
The so-called genomic test measures the activity of genes that control the growth and spread of cancer, and can identify women with a low risk of recurrence and therefore little to gain from chemo.
“More and more evidence is mounting that there is a substantial number of women with breast cancer who will not need chemotherapy to do well,” said Dr. Rachel A. Freedman, a breast cancer oncologist at the Dana-Farber Cancer Institute in Boston. She was not involved in the study.
The researchers estimated that their findings, published Wednesday in The New England Journal of Medicine, would apply to 35,000 to 40,000 women a year in the United States, and 60,000 to 70,000 in Europe. They are patients with early disease who because of tumor size, cancerous lymph nodes and other factors would normally be prescribed chemo.
Genomic tests, which doctors have been using for about 10 years in some breast cancer patients, are part of a growing effort to spare women from chemo and its harsh side effects whenever it is safe to do so. But the decision to forgo a potentially lifesaving treatment is never taken lightly, and doctors have been eager for more data to make sure they are on the right path.
The new study is one of the largest and most rigorous trials of genomic testing, and offers reassurance to doctors and patients that the technology can be trusted to help identify patients who do not need chemo. But an editorial accompanying the report said the study was not the final word, and additional research now underway would provide more clarity. Although women who skipped chemo had low recurrence rates, their rates were slightly higher than those of women who had chemo.
The results of the study will be of most use for cases that have fallen into a gray zone, when the disease is in an early stage but has some anatomical features that suggest it may be aggressive. But the genomic test says it is low risk.
“We all see these patients in our practice all the time,” Dr. Freedman said. “What do you do with that person?”
The study involved women with early cases of the most common type of breast cancer: hormone-sensitive tumors that test negative for a receptor called her2. In the United States, about three quarters of breast cancers are that type.
Early stage in the study referred to Stage 1 or 2, meaning the tumors were generally no bigger than five centimeters and had spread to no more than three lymph nodes. The study was done in Europe, where “early stage” includes somewhat larger tumors than would be included in the United States.
More than half of the breast cancers in the United States are diagnosed at early stages.
The research involved 6,693 women with early-stage breast cancer at 112 hospitals in nine European countries. The study was paid for by grants from governments, drug companies and charitable groups. Agendia, the company that markets MammaPrint, did the testing at no cost.
The women had the usual initial treatments — surgery, hormonal therapy and radiation. Then, researchers determined whether each woman had a high or low risk of recurrence based on genomic testing and on clinical features like tumor size and number of positive lymph nodes. Sometimes, the clinical and genomic risks did not match.
MammaPrint looks at the activity of 70 genes. In a low-risk tumor, 50 genes are turned off and 20 are active, according to Laura J. van ’t Veer, a molecular biologist at the University of California, San Francisco who was an author of the study and a developer of the test. In high-risk cases, 50 genes are on and 20 off.
The researchers were especially interested in the women — about a quarter of those in the study — who seemed to have a high clinical risk but a low genomic risk.
Dr. Fatima Cardoso, an author of the study and a breast oncologist at Champalimaud Clinical Center in Lisbon, said that traditionally, women with early cancer but a high clinical risk were usually given chemotherapy. She said that doctors knew that not all would benefit from it, but gave it to all anyway to err on the side of caution, because they could not identify which women did not really need it.
The main goal of the study was to find out whether women with a high clinical risk but a low genomic risk could safely forgo chemo.
There were 1,550 women with high clinical risk and low genomic risk. They were assigned at random to be treated according to their genomic risk or their clinical risk. So some received chemotherapy, and others did not. Then the researchers watched to see if any had distant spread of the cancer to other organs, which is often fatal.
After five years, among those who did not receive chemotherapy, 94.4 percent had no distant spread. Those who received chemo fared slightly better: 95.9 percent had no distant spread.
“We have to continue to follow these patients and see what happens at 10 years,” Dr. Cardoso said.
But given the small difference so far, the researchers said that it was safe for women with early disease and high clinical risk, but low genomic risk, to skip chemotherapy. The findings, they said, mean that 46 percent of women with early-stage disease who are thought to be at high clinical risk may be able to skip chemo.
An editorial accompanying the article praised the research but sounded a note of caution. The authors, Dr. Clifford A. Hudis and Dr. Maura N. Dickler, from Memorial Sloan Kettering Cancer Center in New York, said that the study was not large enough to be sure that the 1.5-percentage-point difference would hold up statistically.
The editorial also noted that other studies of genomic tests had identified groups of women in whom the five-year recurrence risk was only 1 percent, and asked what level of risk was acceptable. Patients’ attitudes also differ.
Dr. Freedman said some women wanted no part of chemo, even if it offered a significant benefit. But, she added, “others line up at the door for almost no benefit, just so they can have peace of mind.”