Study: Patient’s Genetic Characteristics May Help Differentiate HER2-Low Advanced Breast Cancers and Guide Treatment Selection

The targeted therapy trastuzumab deruxtecan (T-Dxd), an antibody drug conjugate, is now an approved treatment of HER2-low advanced breast cancers. In a new study led by Yale Cancer Center researchers at Yale School of Medicine, their findings revealed important differences in the genetic makeup of HER2-low advanced breast cancers — a discovery that could lead to better treatment options for patients.

“If genomic alterations that are particular to HER2-low tumors were to be found, this could potentially aid in patient selection for trastuzumab deruxtecan and also for the development of novel agents or combinations of therapies targeting the HER2-low patient population,” said first author of the study Adriana Kahn, MD, a member of Yale Cancer Center and an assistant professor of medicine (medical oncology) at Yale School of Medicine

Researchers examined 2,086 breast cancer cases and used a method called comprehensive genetic profiling to look at the entire set of a person’s cancer cells. Patients were divided into three groups: HER2-negative, HER2-low, and HER2-positive.

The study showed that that HER2-low patients were generally older than those with HER2-negative breast cancer, suggesting that age might play a role in the genetic makeup of HER2-low cases. HER2-low cases were also more common in breast cancers that were positive for hormone receptors. Researchers say it’s an important finding because it shows that the genetic characteristics of HER2-low cases can be different depending on the presence of hormone receptors.

“The genomic differences we have encountered that are particular to HER2-low patients should be further confirmed and explored in prospective trials to hopefully allow us to better understand and treat our patients,” Dr. Kahn added.

While some genetic traits were similar across all three groups, researchers identified differences in HER2-low cases despite stratifying patients by their tumor’s hormone receptor expression, including how HER2-low cancers were less likely to have changes in the p53 gene when compared to HER2-negative cases.

Maryam Lustberg, MD, the director of the Center for Breast Cancer at Yale Cancer Center and Smilow Cancer Hospital joined Dr. Kahn as the study’s senior author. Lajos Puztai, MD, was also a Yale co-author. The research team will present their findings at the San Antonio Breast Cancer Symposium (SABCS) on December 7.