Some early-stage, post-operative breast cancer patients meeting a certain genetic profile can avoid potentially dangerous and expensive chemotherapy with only a slightly lower survival rate, and without the cancer spreading, a major study published in The New England Journal of Medicine Wednesday has found.
The study said that 46 percent of subjects who were classified as high-risk by traditional clinical criteria but low-risk according to their genetics could skip chemo and expose themselves to just a slightly greater risk – 1.5 percent -- of the cancer metastasizing after five years.
Those who received chemo had a 95.9 percent rate of success after five years, compared to 94.4 percent of those who did not get the treatment.
In other words, the difference between opting for chemo or not is so small that "You would have to treat 100 of those [patients] with chemotherapy for the benefit of one," said Dr. Laura van't Veer, one of the leaders of the breast oncology program at the University of California, San Francisco, who helped develop the test that the researchers used to determine the genetic risk level of recurrence for each patient.
That still may be enough of a difference for some patients and their doctors to choose chemo. In an editorial that accompanied the study in the NEJM, Dr. Clifford A. Hudis, chief executive officer of the American Society of Clinical Oncology, and Dr. Maura Dickler, a researcher who also treats breast cancer patients at Memorial Sloan Kettering Cancer Center in New York City, said the decision whether to undergo chemo or not won't be a slam dunk, even with the new information provided by the test.
"(A) difference of 1.5 percentage points, if real, might mean more to one patient than to another," they wrote. "Thus, the stated difference does not precisely exclude a benefit that clinicians and patients might find meaningful."
Dr. van't Veer said, nevertheless, many whose risk is low according to the test would opt out: "It doesn't mean you should not acknowledge [the risk], but it's such a low benefit that many breast cancer patients will decide not to take chemotherapy."
Dr. Fatima Cardoso, the study's lead author and a breast cancer specialist at the Champalimaud Clinical Center in Lisbon, Portugal, said that women at her clinic shown to be at low genetic risk through MammaPrint usually choose to forego chemo.
"But there always [are] some patients for whom 1 percent benefit is enough — and you need to respect the wishes of each individual patient."
Side effects from chemotherapy can include hair loss, mouth sores, diarrhea, early menopause, dental issues and in rare cases leukemia and other diseases.
MammaPrint is priced at $4,200 and is covered by some insurance in the U.S.
The phase 3 study, called MINDACT, enrolled 6,693 breast cancer patients, recruited from 2007 to 2011 from 112 hospitals in nine European countries. Patients were between 18 and 70.
The point of the study was to compare a 70-gene risk-assessment test called MammaPrint to a risk classification system that ignores genetics but takes into account clinical characteristics like a patient's age, tumor diameter, and whether the cancer has spread to the lymph nodes. The researchers wanted to know whether patients who were classified as high-risk according to the clinical criteria but low-risk according to MammaPrint had better or worse outcomes if they did not receive chemo.
Dr. van’t Veer and other researchers in the study are part of a company, Agendia, that has sold MammaPrint commercially in the U.S. since 2008.
A total of 1,550 patients fell under a group with either high clinical and low genetic risk profiles or low clinical and high genetic risk profiles. Those patients were then randomized into either receiving chemo or not. After five years, those who had not received the treatment were 1.5 percent more likely to avoid seeing the cancer spread into distant areas than those who had received the treatment.
The study focused on women with stage 1, stage 2 and operable stage 3 breast cancer, with up to three affected lymph nodes.
About 246,660 patients will receive an invasive breast cancer diagnosis in 2016, according to the American Cancer Society. Of that group, van't Veer estimated that MammaPrint could flag 35,000 to 40,000 breast cancer patients as being in a position not to pursue chemotherapy and still experience a statistically small chance of recurrence.
Karuna Jaggar, the executive director of Breast Cancer Action, a breast cancer advocacy organization, thought the study was significant, and a win for what's known as precision medicine -- tailoring treatments according to the individual characteristics of patients.
"We know that there are harms that come with any treatment, whether it's surgery, radiation or chemotherapy. And it's very important for patients to be able to weigh the risks and benefits when making their own treatment decisions."
Jaggar said the financial fallout from receiving chemotherapy can be significant. Besides the cost of treatment, which she said can reach well over $100,000, "There's a lot of data that shows even several years after treatment, women who have undergone chemotherapy are more likely to be un- and underemployed."
NPR contributed to this report.