By Erin Allday
A large percentage of women with early-stage breast cancer who have been identified as having a high risk of recurrence should consider forgoing chemotherapy based on the biological makeup of their tumor, according to research published Wednesday.
Nearly half of early breast cancer cases that meet traditional criteria for high risk can be treated just as effectively without chemotherapy as with it, according to the study, which used genetic testing to analyze tumors. Those patients can instead be treated with surgery and, as needed, hormone therapy, researchers said.
The findings, published in the New England Journal of Medicine, are among the strongest to demonstrate how personalized medicine — applying treatments based on the genetic makeup of individuals or their disease — can be used to refine cancer therapies and, in this particular case, avoid over treating individuals, doctors said.
“Many breast cancer patients are over treated by chemotherapy. That’s been known,” said Dr. Laura van ‘t Veer, a UCSF molecular biologist who co-wrote the new paper. “However, we needed more precise measurements to tell us who are the ones who can really forgo chemotherapy.”
The study used a test called MammaPrint, developed by van ‘t Veer and colleagues from the Netherlands Cancer Institute, where she worked before joining UCSF in 2010. Van ‘t Veer co-founded a company, called Agendia, that markets MammaPrint.
The MammaPrint test looks at 70 genes known to be associated with risk of cancer recurrence. The test, which has been widely used throughout Europe, was approved by the U.S. Food and Drug Administration in 2007, but it has been slow to catch on with American physicians, said van ‘t Veer and other doctors.
The new report is a landmark study that should have immediate implications for breast cancer care, said Dr. Laura Esserman, director of UCSF’s Carol Franc Buck Breast Care Center, who works with van ‘t Veer but was not part of the MammaPrint research.
“This kind of study 100 percent tells us that biology matters. It’s a huge step forward,” Esserman said. “We’re moving more and more into one size doesn’t fit all for cancer. This solidifies our ability to act on that.”
The study involved 6,693 women in Europe who were diagnosed with early-stage breast cancer. The risk of recurrence for each woman was determined two ways: by the MammaPrint test and by a more traditional clinical test that looks at the patient’s age, whether she’s gone through menopause and the size of the tumor, among other things.
Women who fell into a high-risk category on both tests received chemotherapy; women who were low risk in both did not. The rest of the women — about a third of the total, for whom the two tests did not match — were randomly assigned to either receive chemotherapy or not.
The study found that for the 1,550 women who were identified as high risk by traditional tests but low risk by genetic testing, the chance of recurrence — about 5 percent after five years — was almost identical whether they received chemotherapy or not. Women who received chemotherapy had a somewhat smaller chance of recurrence, but the result was not statistically significant.
In the United States, about 230,000 women are diagnosed with breast cancer every year, the majority of them with early-stage cancer, meaning it’s located only in the breast and, in some cases, the lymph nodes.
Without chemotherapy, roughly 25 percent of women with early-stage cancer will develop an invasive tumor in another part of their body — what’s known as metastasizing — after 10 years, van ‘t Veer said. But because there hasn’t been a good way to determine who is at risk of metastasizing, about 80 percent of those women receive aggressive chemotherapy treatment in the United States, she said.
That matters because chemotherapy involves toxic drugs that can have immediately unpleasant side effects — including hair loss, nausea and cognitive impairment — and cause long-term problems like heart disease and even secondary cancers. Some women may be unable to work or stick to their usual routine during the many months of chemotherapy treatment.
It can be tough to persuade doctors and patients to skip a treatment like chemotherapy that has become a standard of care, van ‘t Veer said. But given the drawbacks of chemotherapy, she expected many people to take note of the new research and consider scaling back care appropriately.
“To do less is always a difficult step. The mantra ‘less is more’ is not so easy to implement,” she said. “I think people have been waiting for this — they needed this level of evidence.”
Karuna Jaggar, executive director of the patient advocacy group Breast Cancer Action, said she welcomed any strong research that allows women to make informed decisions about their own care.