After breast cancer tumors are removed, many women undergo chemotherapy to eradicate any remaining cancer cells and reduce the risk that the disease will recur. The drugs can make them nauseous and anxious and lead to hair loss.
But a blood test under development at the Johns Hopkins University could reduce the number of women who need chemotherapy significantly by revealing who has residual cancer cells after surgery to remove the tumors.
"Oncologists are over-treating breast cancer because they don't know who to treat" after surgery, said Dr. Ben Ho Park, a Hopkins associate professor of oncology working on the test. "Wouldn't it be great if we could tell patients they're actually free of their cancer?"
This is one of many avenues researchers are following in the hunt for simple, useful blood tests for breast cancer, the most common kind for women after skin cancer, according to the U.S. Centers for Disease Control and Prevention. Every year more than 200,000 women are diagnosed and 40,000 die.
Most tests remain many years away, if they ever become commercially available. Eventually they may be able not only to reliably predict if breast cancer is likely to return, but to diagnose the disease before there are symptoms and track the effectiveness of treatment.
Most testing now isn't so simple. Just to differentiate the type of breast cancer a patient has, for example, surgeons must examine a small piece of the tumor under a microscope.
A blood test widely used now only identifies the small number of women with inherited gene mutations that increase the risk of eventually developing breast cancer. There are some blood tests to show if cancer has recurred, but they are often inaccurate.
Park's test seeks to identify with certainty the 30 percent of early-stage breast cancer patients who will have a recurrence so they can get additional therapies such as chemotherapy, while those not expected to get the disease again can be spared the toxic and expensive treatment.
The test would look for DNA molecules that cancer cells shed into the blood. In early trials, the test was able to tell the difference between these cancerous DNA molecules and normal ones. Now a larger trial at several medical centers is planned.
Park said the test could be easy, quick and cheap to perform in a lab — eventually.
"A lot of companies may jump the gun and begin offering blood tests, but it's still all research," Park said. "We need to prove this is as good as we think it is."
Beth Thompson said making treatment decisions without knowing her chances of recurrence was among the toughest parts of her breast cancer diagnosis nine years ago.
A nurse researcher fairly new to Baltimore, the Phoenix mother of four was shocked during her first mammogram at 40 to learn she had a tumor. She was told twice she probably didn't need chemotherapy; then another small invasive tumor was spotted that could have been trouble.
Doctors estimated she had a 20 percent chance of cancer returning after surgery, 10 percent with chemotherapy and 5 percent if she also took a drug that was still fairly new called Herceptin that targeted specific proteins in cell membranes.
"It's scary to make decisions without all of the information you would like," Thompson said. "As a young person with young children, your knee-jerk reaction is to be as aggressive as possible."
Ultimately, Thompson decided on both treatments, though her doctor told her a young patient had just died after taking the Herceptin, a pill Thompson would need to take for a year. The weeks of chemotherapy meant hours at a time in a chair with an IV in her arm, hair loss and increasing fatigue and nausea.
She also decided on a bilateral mastectomy to prevent a recurrence or a new cancer, though research shows no better outcomes.
Nine years later, she is cancer-free, but she doesn't know if she actually prevented a recurrence. She discusses her decisions routinely now that she has become a nurse navigator at Hopkins' LiveWell Center for young women with breast cancer.
"If someone was able to say I could have definitely skipped chemo, I would have been delighted," she said. "Or that the Herceptin wasn't necessary? We're just not there yet."
Knowing with certainty which treatments would help which patients would be a huge advance, said Dr. Eric P. Winer, director of breast oncology in the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute in Boston and a spokesperson for the American Association for Cancer Research.
Breast cancer is a set of diseases, he said, and generally doctors know the most advanced treatments for some kinds are ineffective for others.
For example, aromatase inhibitors, developed by a University of Maryland researcher, lower levels of the hormone estrogen that fuels tumors in some breast cancer. But they don't work on breast cancer lacking estrogen receptors.
Winer said other new tests could show specific gene defects to target, or if there are no good targets, which is the case in some breast cancers and some recurrent, or metastatic, cancers.
"We need to develop predictive tests that tell us who will benefit and who would not, so we don't waste drugs and dollars," he said. "We need to target [therapies] to people who will benefit most."
That's a goal of the National Cancer Institute's Cancer Diagnosis Program, which funds research in labs at Dana-Farber, as well as Hopkins and the University of Maryland and other cancer centers.
The hope is to find new, targeted drugs, including for the minority of cases that are so-called triple negative, which don't respond to hormonal or other new treatments, said Tracy G. Lively, associate chief of the program's Diagnostics Evaluation Branch.
Her program funds research based on its promise and feasibility. She said early detection tests would be the hardest to develop because the DNA shed by small new tumors would be diluted in large volumes of blood. Tests would need to be what researchers call "sensitive and specific," or reliably able to identify those with the disease and those without.
Developing blood tests to track the effectiveness of treatment and disease recurrence would be less difficult, she said, because doctors would know what they were looking for after breast cancer is confirmed.
"People are really pressing ahead on all of these fronts," Lively said. "But everything has to be tested. It may seem like it has promise, but it might be disappointing."
Despite the challenges, the search continues for a variety of blood tests, including diagnostic ones.
The primary method of testing for breast cancer now is the mammogram, imaging that is uncomfortable and sometimes inconclusive. That leads to more tests to confirm or rule out disease, potentially causing unwarranted alarm in patients.
A new test under development at the University of Maryland likely wouldn't replace mammograms but could augment them or allow less frequent imaging. The test looks for a certain protein called GP88 that is associated with estrogen-receptor positive breast cancer, the most common type.
Past studies suggest GP88 can predict who will have a disease recurrence, said Dr. Katherine Tkaczuk, professor of medicine and head of the breast evaluation and treatment program at Maryland's Greenebaum Cancer Center.
Tkaczuk and partners at Columbia-based A&G Pharmaceutical Inc. are launching a trial to see if it can be used to help diagnose early breast cancer just by its existence in a patient's blood.
They will test 700 women with no history of breast cancer at the time of their annual mammograms. If the test reliably detects cancer, it could more easily and less expensively screen large groups of women with no access to imaging.
The test could also aid women whose images weren't clear because of dense breasts or another condition, or who avoided the test because of discomfort or inconvenience. Or women in general may be able to have mammograms less frequently, Tkaczuk said.
"This test has potential, if it's sensitive and specific enough," she said. "For certain patients, maybe it wouldn't be used exclusively, but maybe every other year. Or you go for a screening mammogram only if the test finds something abnormal. I think a lot of women would welcome that."