The era of immunotherapy has ushered in dozens of new treatment options for some patients with a number of cancer types. The U.S. Food and Drug Administration (FDA) approved the first checkpoint inhibitor—ipilimumab (Yervoy®)—in 2011 to treat patients with metastatic melanoma. Today, six approved checkpoint inhibitors are being used to treat some of the most common cancers. But while patients with some types of lung, kidney, bladder and other cancers are taking these new drugs, most patients with breast cancer, the most commonly diagnosed non-skin cancer in the United States, are still waiting.
“ We get so many questions from patients asking us about immunotherapy and breast cancer. There are so many clinical trials, but so far, it is not an FDA-approved treatment.” - Sramila Aithal, MD -Hematologist-Oncologist and Medical Oncologist at our hospital in Philadelphia
Checkpoint inhibitors work by blocking signals that cancer cells use to hide from the immune system. Most of these drugs target the PD-1 or PD-L1 signal receptors, either on immune cells or cancer cells. Research shows that patients with triple-negative breast cancer, which accounts for up to 20 percent of all cases, appear to respond better to checkpoint inhibitors than patients with other types of breast cancer. Other studies indicate that some breast cancers may have high levels of PD-L1.
But scientists don't fully understand why some cancers respond to these drugs and others don't. "The question is: What makes the triple-negative cancer more prone to respond?" says Shayma Kazmi, MD, Medical Oncologist at our hospital in Philadelphia. "Not all lung cancers respond to immunotherapy. Not all melanomas respond. There is a subsection of cancers that tends to be responsive. And there are multiple ways to assess that sensitivity. PD-L1 is just one of them, and it's not perfect."
Triple-negative breast cancers also tend to have high levels of T-cells called tumor-infiltrating lymphocytes (TILs), which may become activated by a checkpoint inhibitor. In an article published in the Journal for ImmunoTherapy of Cancer, researchers theorized that "tumors with high TILs may also have increased PD-L1 expression, which might be the reason that triple-negative breast cancer seems to demonstrate the most robust clinical response to immune checkpoint inhibitor therapy, but further investigation is needed."
Still, some breast cancer patients may be treated with a checkpoint inhibitor in certain situations. For instance:
The patient qualifies for approved immunotherapy treatment because her tumor has a specific genetic feature. In May 2017, the FDA took the historic step of approving a cancer drug based not on a tumor's primary location but on a specific genetic feature found in the cancer’s DNA. The approval allows pembrolizumab (Keytruda®) to be used to treat patients with tumors that have one of two specific genetic features: microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). These gene mutations are more commonly found in gastric cancers, but are occasionally found in breast and other cancers.
Some patients may qualify for a clinical trial. Currently, dozens of trials are researching several checkpoint inhibitors as potential breast cancer treatments. The drugs are being tested by themselves, in combination with other checkpoint inhibitors and in addition to other treatments such as chemotherapy. A trial may allow a doctor to prescribe drugs as off-label treatment. This is the practice of prescribing the drug to treat a cancer type that has not approved for immunotherapy treatment by the FDA. Patients participating in the Targeted Agent and Profiling Utilization Registry (TAPUR) study, for instance, may be prescribed anti-cancer drugs by matching them to specific genomic mutations found in the patients’ tumors.
"The published data shows there seem to be more responses in triple-negative breast cancer than in other types, but the data is still premature," Dr. Aithal says. "We still need more time. But there are a ton of studies that are ongoing."