HER2-positive breast cancer—which accounts for about 20% of all breast cancers—grows at a much more rapid rate than other types of breast cancers. This is because it contains a protein, called the human epidermal growth factor receptor 2, which stimulates cells to grow faster than normal.
“This means the protein is overexpressed,” says Haythem Ali, M.D., a medical oncologist at Henry Ford Health. “Here’s an analogy: Instead of having, for example, just 10 antennas on the surface of its cells, the HER2-positive cell has 1,000 antennas on the surface of its cells. And if you have a lot of antennas, you’ll pick up growth signals a lot stronger.”
Because HER2-positive breast cancer grows so quickly, the median survival used to be somewhere between nine and 12 months. But thanks to a monoclonal antibody treatment that specifically targets the HER2 protein, the median survival for HER2-positive breast cancer is now around three and a half years. (Dr. Ali, however, has a patient who has been with him since 2005.)
“Monoclonal antibodies are copies of human antibodies, created in a lab, that bolster your immune system to fight off disease,” says Dr. Ali. “For HER2-positive breast cancer, these antibodies are specifically designed to attach themselves to the HER2 protein. By doing that, they make the HER2 protein inactive. They basically ‘jam’ the signal over the antenna, so the signal can’t be received anymore.”
But monoclonal antibody treatment isn’t effective for people who have HER2-low breast cancer—meaning they have lower levels of the HER2 protein. In fact, people with HER2-low breast cancer used to be categorized as HER2-negative, since treatment targeting the HER2 protein hasn’t worked for them.
Now, however, the Food & Drug Administration (FDA) has approved Enhertu, the first drug to treat HER2-low breast cancer.
Breakthroughs In Treating HER2 Breast Cancer
“Enhertu combines monoclonal antibody therapy with chemotherapy,” says Dr. Ali. “Here's how it works: A bit of chemotherapy is attached to an antibody. The antibody then delivers the chemotherapy to the HER2 cancer cells. Instead of just jamming the signal with antibodies, the antibodies deliver chemotherapy to kill the HER2 cancer cells.”
In a clinical trial, participants who received Enhertu lived about twice as long without their cancer growing as opposed to participants who received only chemotherapy. They also lived, on average, about six months longer.
Chemotherapy has historically been a systemic treatment, meaning it’s delivered into the bloodstream and circulates everywhere in the body—not just where the tumor is—so it can affect healthy cells as well as cancer cells. This is why it can cause side effects like nausea, fatigue, brain fog, neuropathy and an altered sense of smell and taste. But packaging chemotherapy so that it targets specific cancer cells not only creates a more potent treatment, but can also lead to lessened side effects.
“It’s delivering chemotherapy in a completely different way," says Dr. Ali. "It allows us to use chemotherapy drugs that we previously kept on the shelf because they were too toxic to use as systemic treatments. But now that we can use them as targeted treatments, they’re becoming useful again. Pairing monoclonal antibody treatment with chemotherapy—it could be game-changing and may pave the way for many cancer treatments in the future.”
Haythem Ali, M.D., is a medical oncologist who sees patients at Henry Ford Health Cancer—Brownstown Township and Henry Ford Health Cancer—Detroit.