A new study suggests that blood tests known as “liquid biopsies” can improve treatment for some people with metastatic breast cancer and help them maintain control of the tumor for more than a year.
For many, it has been here for a long time. More than a decade ago, researchers and investors predicted that a liquid biopsy sensitive enough to detect tumor cells and DNA in the blood would be a “game changer” in the field of cancer.
Liquid biopsies have not been replaced by standard cancer screening methods such as mammograms and colonoscopy, but new research shows that blood tests can help doctors monitor cancer and select the treatments that are most likely to work.
Liquid biopsies are so sophisticated that they can detect ultra-small bits of DNA leaking from tumor cells and floating freely in the blood. The most sensitive fluid biopsy, like the biopsy used in new research, goes a step further to detect ominous changes in the major proteins of cancer cells.
The study, published Sunday in the New England Journal of Medicine and at the American Society of Clinical Oncology’s annual meeting in Chicago, focused on people whose breast cancer is fueled by estrogen. The most effective treatments for this type of advanced disease include drugs designed to target specific proteins in breast cancer cells. Once these proteins are mutated, the drug will no longer function and it will only be a matter of time before the cancer will start to grow again.
By detecting these mutations, liquid biopsies act as an early warning system that people need another drug, said Dr. Nicholas Turner, research co-author and professor of molecular oncology at the UK Cancer Institute and Royal Marsden Hospital in the UK.
In a new study, those who changed treatment based on the results of a fluid biopsy were twice as likely to control tumors than those who did not change treatment.
Turner said the approach offers significant improvements compared to current practices.
Now, doctors are doing imaging tests, such as CT scans and PET scans every three months to find signs of cancer treatment not working. These scans allow doctors to check if the tumor is growing larger.
The study found that liquid biopsies could detect mutations up to nine months before the change was revealed on the scan, Turner said. This gives people the opportunity to abandon ineffective treatments as quickly as possible and switch to those who are more likely to control cancer.
About one in ten people in the study found that their cancer developed mutations that made current treatment more effective.
“We have a very effective treatment, but they can go away,” Turner said. “And once they wear out and the cancer starts to grow again, it can make people feel less concerned. If you have cancer in your bones, it can start to cause pain.”
Researchers mutated half of the 315 people to quickly change treatments, with the other half randomly assigned to continue with the medication as usual, said Dr. Massimo Cristofanilli, author of the study at Weill Cornell Medicine and Newyork-Presbyteran Hospital and author of breast oncology. One percent of study participants were male.
For those who changed treatment early, researchers replaced the hormone drug they were taking with an experimental cancer drug called Camizestrant, which has not yet been approved by the Food and Drug Administration. Kamisé Strant interferes with the ability of estrogens to stimulate cancer growth. AstraZeneca funded clinical trials built on early basic research funded by the National Institutes of Health, Christofanilli said.
Research shows that in study participants who switched to Camidestrand, the cancer remained stable with no tumor growth for 16 months. This compared to nine months of people who did not switch medication, according to the study.
One year later, 61% of study participants who switched to Camidestrand had a stable illness, compared to 33% of those who did not change treatment. Two years later, 30% of those who switched were still stable illnesses, compared to 5% who were not.
Study participants who switched treatment reported overall health and quality of life for 23 months compared to others in the study who reported a deterioration in health and quality of life after 6.4 months.
“If you switch treatments at the right time, you can put the cancer to sleep, prevent it from progressing, and keep the person in good condition,” Turner said. “Many of my patients go back to work and continue to live normal lives. They get time with their kids.”
Camizestrant is available only in clinical trials, while the similar drug Faslodex has been approved by the FDA.
Unanswered Questions
Kamisé Strant caused more side effects than hormonal medications, but most people continued to take it. Approximately 1.3% of participants stopped taking kamidestrant due to side effects, compared to 1.9% who discontinued treatment with hormonal medication.
Camidestroent side effects included a decrease in white blood cells and a slower than usual heart rate. Those taking the medication were more likely to see flashes and floating spots in peripheral vision.
Heather Parsons, a medical oncologist at the Dana Farmer Cancer Institute in Boston and an assistant professor of medicine at Harvard Medical School, said he was not involved in the study. “This is an important study, but the results are immature.”
“We need to understand whether it will help change treatments early or whether it will lead to more toxic treatments being used sooner,” Parsons said.
This study did not answer the major questions about whether new approaches would help patients live longer. Turner said he plans to follow participants to know if the new regimen improves survival.
Thanks to better treatment, people with metastatic breast cancer live around five years after the cancer spreads. That means it can take years to detect whether one treatment extends life over another, Turner said.
Doctors don’t know if all patients respond in the same way as the patients in the study. Most of the people in this study were white and few black participants were involved.
According to the American Cancer Society, in addition to 2,800 cases of men, approximately 317,000 cases of invasive breast cancer will be diagnosed in women in the US this year. Approximately 42,170 people die from the disease.
Dr. Kelly Shanahan, a doctor who has lived with estrogen-driven metastatic breast cancer since 2013, called the results “exciting” and “attractive.”
“If I’m in this situation, especially if the side effects of Camidestrand are accepted by me, I certainly want to talk about early switches,” said Shanahan, director of the research committee at Metavivore, an advocacy group for people with metastatic disease.
Other uses for liquid biopsy
Scientists are developing liquid biopsies to improve the treatment of many types of cancer.
In a study published in the Journal of New England Medicine in 2022, Australian researchers used tumor DNA in the blood to predict whether people with early colon cancer will need chemotherapy after surgery, and who could skip it without increasing the risk of recurrence. Many doctors currently use liquid biopsies when treating colon cancer patients, but the tests used in this study are not available in all countries, said Dr. Jeanne Tie, the first author of the study and a senior researcher in oncology personalized at the Elizahall Institute of Medical Sciences in Victoria, Victoria, Australia.
Liquid biopsies are being studied for screening healthy people for cancer.
For example, the FDA last year approved approval, called Shield, the first blood test, for screening for colorectal cancer. However, blood tests are not an alternative to colonoscopy, but they are still required as part of a definitive diagnosis, and neither the American Cancer Society nor the American Preventive Services Task Force have approved the Shield as a form of cancer screening. Shield tests correctly identified 83% of colon cancer, but have not been shown to be life-saving.
Doctors may one day use a liquid biopsy to provide further answers when mammogram results are unknown, especially for women with dense breasts. He hopes that blood tests will reduce the number of painful needle biopsies.
