fbpx A New Drug for HER2-Low Breast Cancer Shows Promise
Three bottles of pills are lined up against a yellow and brown pattern of cancer cells.
Three bottles of pills are lined up against a yellow and brown pattern of cancer cells.

A New Drug for HER2-Low Breast Cancer Shows Promise

Enhertu significantly improves survival and cancer-progression rates for metastatic patients.
Stephanie Anderson Witmer
Written by

Stephanie Anderson Witmer

A new drug for metastatic breast cancer significantly improves survival and cancer-progression rates for patients with the newly defined subtype, HER2-low breast cancer, according to a July 2022 study published in the New England Journal of Medicine.

During the DESTINY-Breast04 clinical trials for the drug trastuzumab deruxtecan (T-DXd), which is sold under the brand name Enhertu, 557 participants with low levels of the HER2 protein in their tumors were randomized to receive either T-DXd or their physician's choice of chemotherapy.

The participants who received T-DXd lived almost twice as long without their cancer progressing and lived six months longer overall than their study counterparts who didn't receive the drug.

Until now, HER2-low cancer patients—who account for most of the cases of metastatic breast cancer—have had limited treatment options. Based on the results of this trial, the Food and Drug Administration (FDA) approved T-DXd in August for the treatment of HER2-low breast cancers that can't be removed with surgery or have spread in the body. Before receiving T-DXd, patients must have already undergone chemotherapy or had their cancer return during or within six months of finishing chemo.

"[T-DXd] is the first HER2-targeted therapy shown to provide clinically meaningful improvement in progression-free and overall survival compared with standard chemotherapy in people with HER2-low metastatic breast cancer," said the study's lead author, Shanu Modi, M.D., an oncologist at Memorial Sloan Kettering Cancer Center in New York City, at a June meeting of the American Society of Clinical Oncology.

Other cancer researchers and oncologists are excited by the study's findings.

"The results of this trial are practice-changing," said William R. Gwin III, M.D., an oncologist at Seattle Cancer Care Alliance and assistant professor at the University of Washington School of Medicine. "The results revealed that in patients with HER2-low metastatic breast cancer, T-DXd shrunk 50 percent of their tumors and helped patients live longer, ultimately proving to be much more effective than standard chemotherapy."

What is HER2?

"HER2 is a protein found on the surface of a variety of cancer cells, most notably in breast cancer," said Bonni Lee Guerin, M.D., an oncologist and director of the Breast Cancer Treatment and Prevention Center at Overlook Medical Center in New Jersey. "The HER2 protein is responsible for promoting the growth of breast cancer cells."

A gene mutation can cause an overabundance of this protein—which occurs in about 15 percent of breast cancers—that creates an aggressive form of the disease known as HER2-positive breast cancer. Cancer cells with a minimal amount of this protein are referred to as HER2-negative.

Two tests are performed to determine a patient's HER2 score; a score of 3+ or higher is considered HER2-positive, and 2+ or lower was called HER2-negative.

But the DESTINY-Breast04 study created a new category, HER2-low, for patients scoring a 1+ or 2+ on a test. About 60 percent of people put into the HER2-negative category have low levels of HER2, said Aisha Ahmed, M.D., an oncologist and researcher at Arizona Oncology in Tucson.

What does this mean for people with breast cancer?

Until now, more attention had been paid to developing treatments for patients with aggressive HER2-positive breast cancer, and those therapies have drastically improved those patients' prognoses, Guerin said.

But most people who get breast cancer don't have the HER2-positive subtype.

"Numerous drugs are FDA-approved to treat HER2-positive breast cancer, however, none have shown benefit in breast cancers with HER2 scores in the 1+ or 2+ range," Ahmed explained.

Doctors have not had effective HER2-targeted therapies to offer HER2-low patients until the recent introduction of a new generation of HER2 antibody drug conjugates, like T-DXd.

"More than half of what we call HER2-negative is now HER2-low, and these women are now eligible for an entirely new type of treatment, and one that would statistically improve their survival," Guerin said.

Patients should talk to their doctors about their HER2 scores, Ahmed recommended.

"If you have metastatic breast cancer that was previously identified as HER2-negative, talk with your doctor about your score, whether you were a 1+ or a 2+, as T-DXd might be an option for you," she said.

Guerin referred to the significance of the study's results as "far-reaching," and researchers are looking at the drug's potential benefits beyond advanced metastatic breast cancer.

"Given the promising results of this study, T-DXd is now being tested in patients with earlier-stage breast cancer to see if these results translate to an even larger number of patients," Gwin said. "In addition, as HER2 is present on many other types of cancer, T-DXd is now being tested in these other tumor types with the hopes it can be effective in these cancers as well."