Cynthia Ma, MD, PhD, Discusses HER2-Targeted Therapy for Patients with HER2-Mutant Breast Cancer

An expert in treating breast cancer discusses potential therapy options for patients with HER2-mutant.

During the American Association for Cancer Research Annual Meeting, CancerNetwork® spoke with Cynthia Ma, MD, PhD, from Washington University in St. Louis, about treating HER2-mutant breast cancer with neratinib (Nerlynx) plus fulvestrant (Faslodex) in a phase 2 clinical trial (NCT01670877). Patients who had HER2 mutations and metastatic disease demonstrated promising responses with the combination.


We all know that HER2 is an established therapeutic target. For example, we routinely test breast cancer for HER2 amplification. We have so many, HER2 targeted agents that are very effective, however, over 70% or 80% of breast cancers are actually HER2-nonamplified or not overexpressed. In those patients, the current HER2-targeted agents are not considered effective. They’re treated with, for example, hormonal therapy or chemotherapy depending on the [estrogen receptor] status. Because of the success of HER2-targeted agents, we’re looking at whether we can expand this to additional people [who may] be eligible to receive them.

Recently, based on genomic sequencing data, studies have found that about 2% to 3% of breast cancers that occur [and are HER2] nonamplified actually have mutations in HER2. Subsequent studies indicate that these mutations actually drive the protein tyrosine kinase activity [that] drives tumor growth, demonstrating that HER2-targeted agents, especially with the HER2 inhibitor neratinib, will be able to inhibit tumor growth. Therefore, we decided to look at neratinib activity in the HER2-mutated, HER2-nonamplified breast cancer. [To] do this will provide another targeted approach for these patients.


Ma C, Luo J, Freedman R, et al. A phase II trial of neratinib (NER) or NER plus fulvestrant (FUL) (N+F) in HER2 mutant, non-amplified (HERmut) metastatic breast cancer (MBC): Part II of MutHER. Cancer Res. 2021;81(suppl 13):CT026. doi:10.1158/1538-7445.AM2021-CT026

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