Genetic Characteristics of HER2-Low Advanced Breast Cancers May Guide Treatment Selection

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Researchers have revealed significant differences in the genetic characteristics of HER2-low advanced breast cancers, which may lead to the development of novel therapeutics for patients, according to recent findings presented by Kahn et al at the 2023 San Antonio Breast Cancer Symposium (Abstract PO4-15-08).


The targeted antibody-drug conjugate fam-trastuzumab deruxtecan-nxki has been approved for the treatment of HER2-low advanced breast cancers.

“If genomic alterations that are particular to HER2-low [breast cancer] 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 [this] patient population,” highlighted lead study author Adriana Kahn, MD, Assistant Professor of Medicine (Medical Oncology) at the Yale School of Medicine and a member of the Yale Cancer Center.

Study Methods and Results

In the recent study, researchers used comprehensive genetic profiling to analyze the cancer cells of 2,086 patients with breast cancer. The patients were then divided into three groups: those with HER2-negative breast cancer, those with HER2-low breast cancer, and those with HER2-positive breast cancer.

The study authors reported that the patients with HER2-low breast cancer were generally older compared with those who had HER2-negative breast cancer, suggesting age might play a role in the genetic makeup of HER2-low breast cancers. Additionally, HER2-low breast cancers were more common among those with hormone receptor–positive breast cancer—demonstrating that the genetic characteristics of HER2-low breast cancers may differ depending on the presence of hormone receptors.

Although some genetic traits were similar across all three groups, the researchers identified differences in HER2-low tumors despite stratifying patients by their tumors' hormone receptor expression. They discovered that HER2-low breast cancers were less likely to have changes in the p53 gene when compared with HER2-negative breast cancers.


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

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.