Immunotherapy refers to treatments that use the body’s own immune system to combat diseases. While immunotherapy hasn’t yet had as big an impact on the treatment of breast cancer as it has on some other cancers, scientists agree on its potential to improve outcomes for many patients with breast malignancies.
Who can be treated with immunotherapy?
A major milestone came in 2019 when the U.S. Food and Drug Administration (FDA) authorized the first use of an immunotherapy drug, in combination with chemotherapy, for a type of breast cancer. In response to the results of a major clinical trial, the FDA approved the immunotherapy agent atezolizumab — plus the chemotherapy agent nab-paclitaxel — for patients with metastatic triple-negative breast cancer that tests positive for the PD-L1 protein and cannot be removed by surgery. (Triple-negative breast cancer, which accounts for about 10-15% of all breast cancers, lacks receptors for estrogen and progesterone and doesn’t carry excess amounts of the protein HER2.)
Atezolizumab is one of a new generation of immunotherapy agents called immune checkpoint inhibitors that unleash a potent immune system attack on cancer. Many cancer cells carry checkpoint proteins like PD-L1 that cause the immune system to withhold its attack. By blocking these proteins, atezolizumab and similar agents allow the attack to proceed. Like other checkpoint inhibitors, atezolizumab is administered intravenously.
What are researchers focusing on now?
While atezolizumab has so far been approved only for patients with advanced cases of triple-negative breast cancer, investigators are exploring whether it can also be helpful at an early stage of the disease.
Checkpoint inhibitors in different groups of patients with triple-negative breast cancer
Several ongoing studies are examining the effectiveness of checkpoint inhibitors in different groups of patients with triple-negative breast cancer. In late 2019, researchers leading the Keynote 522 trial reported that patients who received the checkpoint inhibitor pembrolizumab plus chemotherapy prior to breast cancer surgery had a significantly higher pathological complete response (no detectable cancer in their tissue samples) than those who received a placebo and chemotherapy. The results held regardless of whether patients’ tumor tissue tested positive for the PD-L1 protein, an encouraging finding.
Because some side effects, which may be reversible, were more common in the pembrolizumab group, the combination of immunotherapy and chemotherapy may be most appropriate for patients with more advanced stages of the disease, the researchers indicated.
The trial leaders have also reported early results on how long study participants survived before the disease recurred. They found fewer recurrences among those who received pembrolizumab, but not enough to be statistically significant. Researchers hope that as more time passes, the improvement will reach statistical significance.
Another trial, the KEYNOTE-119 study, found that patients with previously treated metastatic triple-negative breast cancer fared no better if they were treated with pembrolizumab than chemotherapy. But a deeper analysis of the results suggested that pembrolizumab may provide a survival benefit to patients whose tumors have high levels of PD-L1.
PARP inhibitors as immunotherapy agents
Laboratory research is also finding promise in immunotherapy as a form of breast cancer treatment. Scientists led by Dana-Farber’s Geoffrey Shapiro, MD, PhD, Jennifer Guerriero, PhD, and Constantia Pantelidou, PhD, and colleagues at Beth Israel Deaconess Medical Center have found that drugs known as PARP inhibitors, which inhibit cancer cells from repairing damage to their DNA, may also act as immunotherapy agents.
In experiments in triple-negative breast cancer, they found that the PARP inhibitor olaparib lures immune system cells called CD8+ T cells inside tumors, where they lead an attack against them. The discovery suggests that combining PARP inhibitors with checkpoint inhibitors may make them even more effective, researchers say. Studies are underway to determine if that is the case.
About the Medical Reviewer
Dr. Tolaney received her undergraduate degree from Princeton University in 1998 and her medical degree from UC San Francisco in 2002. She subsequently completed her residency in Internal Medicine at Johns Hopkins University, and fellowships in hematology and medical oncology at Dana-Farber Cancer Institute. She obtained a Masters in Public Health from the Harvard School of Public Health in 2007.
In 2008, she joined the staff of Dana-Farber Cancer Institute and Brigham and Women's Hospital, where she is a medical oncologist and clinical investigator in the Breast Oncology Center. Her research focuses on the development of novel therapies in the treatment of breast cancer.