A new form of immunotherapy treatment — the first of its kind for breast cancer — is showing promising results in early research.
The treatment combines a technique called cryoablation, or freezing of the tumor, with an immunotherapy drug that has already proved effective in advanced melanoma, an aggressive form of skin cancer. The results of this early-stage investigation were presented yesterday at the American Society of Clinical Oncology ’s annual meeting in Chicago.
“Attempts have been made to harness the immune system as an anticancer mechanism for more than 100 years, but progress in this field has been relatively modest until recently,” says Heather McArthur, a Memorial Sloan Kettering breast oncologist who was the senior author of two studies reporting the findings. “However, given the recent successes in treating melanoma, we are looking at immune therapies in other types of solid tumors, including breast cancer.”
Making Tumors More Accessible to Treatment
The drug employed in this study is ipilimumab (Yervoy®), which was developed largely by Memorial Sloan Kettering investigators for the treatment of melanoma. Ipilimumab works by blocking a protein called CTLA-4, which normally puts the brakes on the immune system. If the brakes are turned off, the immune system is able to mount a robust response and ideally destroy tumor cells.
The role of ipilimumab is being actively investigated in a number of solid tumors “Our approach is unique, however, in that it combines tumor freezing with immune stimulation. The treatment is based on that idea that a tumor mass is difficult for the immune system to infiltrate and digest. But if you break the tumor mass down into tiny fragments, the immune system will have an easier time processing it,” Dr. McArthur explains.
In this technique, investigators use cryoablation to break the tumor into smaller pieces. Using MRI for guidance, a small needle is inserted into the tumor to create an ice ball, which freezes it and breaks it into tiny fragments.
The patients are also given a single dose of ipilimumab. The intent of the treatment is to enable the immune system to recognize breast cancer fragments, remember that information, and consequently seek out and destroy any tumor cells that may appear in the body if the cancer recurs months or even years after surgery.Back to top
Evaluating Safety with a Stepwise Approach
The women who participated in this pilot study had newly diagnosed, early-stage disease and had already decided to have a mastectomy.
The first group of six patients underwent cryoablation alone to make sure that it wouldn’t interfere with the ability to later undergo mastectomy, which is intended to cure the cancer. The second group of six underwent immune therapy alone, receiving a single dose of ipilimumab to ensure there were no unexpected side effects.
After confirming that the two approaches were safe on their own, six additional patients were given the full treatment of cryoablation and a single dose of ipilimumab before their surgery. The women were then followed for three months to measure their immune responses and to make sure the treatment did not compromise the standard of care.
“The primary goal of the study was to show that we can combine the two strategies of cryoablation and immune stimulation without compromising a woman’s ability to have her curative-intent surgery, and that’s what we were able to demonstrate in this study,” Dr. McArthur said.
“This was also a unique opportunity to be able to collect tissue samples from before any treatment had been given and then again afterward, and to compare the changes in the tumor cells,” she continued. “Based on the tissue and blood analyses, performed in partnership with [physician-scientist] Jedd Wolchok and our collaborators at the Immune Monitoring Facility, we found that there was indeed a signal of immune activity with the combination of cryoablation and immune stimulation.”
Based on those findings, Dr. McArthur expects a larger study to launch sometime in the fall.Back to top