More patients can benefit from highly effective breast cancer drugs that are already available, according to DNA sequencing studies by researchers at Washington University School of Medicine in St. Louis and other institutions.
The investigators found that some women with the HER2 negative subtype may benefit from anti-HER2 drugs even though standard tests don't indicate they are candidates for the drugs.
"These patients are going to be missed by our routine testing for HER2 positive breast cancer," says Ron Bose, MD, PhD, assistant professor of medicine. "Currently they're not going to receive a HER2 targeted drug because we don't have a way to identify them. And we predict they are going to have a more aggressive form of breast cancer."
Bose, who treats patients at Washington University's Siteman Cancer Center at Barnes-Jewish Hospital, will present the data Dec. 7 at the San Antonio Breast Cancer Symposium.
Today, a type of breast cancer known as HER2 positive is treated with drugs that inhibit the function of the HER2 protein. To be classified as HER2 positive, a patient must have more than the normal two copies of the HER2 gene. Too much HER2 drives tumor growth and some HER2 positive patients may have as many as 20 copies of the gene. Doctors test for this gene "amplification" in every patient diagnosed with breast cancer. It must be present for a woman to receive anti-HER2 drugs.
But instead of multiple copies of the gene churning out too much HER2, some patients deemed HER2 negative based on standard testing may have mistakes in just a few "letters" of the DNA in their two gene copies that result in excess activity of the protein. Bose and his colleagues estimate that these undetected HER2 mutations – rather than the HER2 amplification -- may be driving tumor growth in 1.5 to 2 percent of all breast cancer patients. With about 230,000 new cases of breast cancer diagnosed in the United States each year, even this modest percentage translates into more than 4,000 patients per year.
The study, led by senior author Matthew J. Ellis, MD, PhD, of Washington University, and published online Dec. 7 in the journal Cancer Discovery, analyzed data from eight DNA sequencing studies, which together included about 1,500 patients. Two of the sequencing studies were conducted by The Genome Institute at Washington University, in collaboration with study co-author Elaine R. Mardis, PhD, co-director of the genome institute.
Of the 1,500 patients, 25 were found to have HER2 mutations without gene amplification. Not all mutations appeared to have the same effect, however. After analyzing 13 of the mutations, seven were found to drive cancer growth. In the laboratory analysis, most of these mutations responded well to the anti-HER2 drugs lapatinib and trastuzumab, both approved by the U.S. Food and Drug Administration. Although two of the mutations were resistant to lapatinib in lab tests, they responded well to neratinib, a newer anti-HER2 drug that is currently in phase II clinical trials.
Bose also cautions that some mutations were found to be "silent," meaning they did not drive the tumor's growth and therefore would likely not respond to anti-HER2 drugs.
The study's findings have led directly to the launching of a phase II clinical trial to test whether patients with HER2 mutations (but not the amplification) will benefit from anti-HER2 drugs. The trial will include patients with stage IV breast cancer classified as HER2 negative. Their HER2 genes will be sequenced to look for mutations. If mutations are present, they will be treated with neratinib in addition to the standard treatment they would otherwise receive.
At Washington University, the trial will be led by Cynthia X. Ma, MD, PhD, associate professor of medicine. The other centers participating in the study are the Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cancer Center and the University of North Carolina, Chapel Hill.
Bose points to this study as an example of the potential value in sequencing the DNA of cancer patients, even when limited to a single gene of interest such as HER2.
"If we can identify mutations that we can act on, that information will help us better guide treatment," Bose says. "In this case, we don't even have to develop new drugs against HER2 mutations. It's just a matter of finding the patients."
Washington University School of Medicine: http://www.medicine.wustl.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
For the first time, researchers have tracked the spread of Ebola, almost in real time, during an outbreak. The virus is quickly changing its DNA. But it's still unclear what these mutations mean.
Think of all the adults you know. Think of your parents and grandparents. Think of the teachers you had at school, your doctors and dentists, the people who collect your rubbish, and the actors you see on TV. All of these people probably have little mites crawling, eating, sleeping, and having sex on their faces.
A trial vaccine against Ebola could be tested on healthy volunteers in the UK in September, says an international health consortium.
The ALS Association has raised more than $94 million in recent weeks via its online ice bucket challenge — compared with $2.7 million this time last year. Now what?
Implant attached to bone in pioneering technique that helps prevent infection and discomfort
A new method for removing allergens from peanuts means help could soon be on the way for the roughly 2.8 million Americans with a potentially life-threatening allergy to the popular food, the U.S. Department of Agriculture said on Tuesday.
Survey finds many social media users hesitate to express opinions unless they know their followers will agree with them
Ebola has a nasty reputation for damaging the body, especially its blood vessels. But when you look at the nitty-gritty details of what happens after a person is infected, a surprising fact surfaces.
You think bringing a new toothbrush to market is easy? The seven-year saga of two dental entrepreneurs struggling to bring their patented brush to consumers suggests otherwise.
Scholars have long tried to understand how culture affects communities. New research argues that the parking behavior of drivers may tell us something about the economic productivity of nations.