Dr Quiroga on the Emergence of HER2-Low in Breast Cancer

Dionisia Quiroga, DO, PhD, medical oncologist, assistant professor, Division of Medical Oncology, The Ohio State University Cancer Center–James, discusses the emergence of the HER2-low categorization in breast cancer as well as current treatment options for patients with HER2-low disease.

HER2-low breast cancer has emerged as a significant area of clinical interest in breast cancer research due to recent clinical updates in the space, Quiroga begins. Previously, HER2 status was often categorized as either HER2-positive or HER2-negative, she says. However, research has revealed that many patients who were previously classified as HER2-negative should be classified as having HER2-low disease, Quiroga details. This category now comprises approximately half of all diagnosed breast cancer cases, Quiroga adds.

Earlier attempts to target HER2-low breast cancer primarily utilized standard HER2-targeted agents, such as trastuzumab (Herceptin) and trastuzumab emtansine (Kadcyla; T-DM1), Quiroga says. Unfortunately, this population was not generally responsive to traditional HER2-targeted therapies, and did not experience benefit with T-DM1, Quiroga reports. However, a breakthrough emerged with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in the phase 3 DESTINY-Breast04 trial (NCT03734029).

In this trial, patients with hormone receptor–positive, HER2-low breast cancer who had previously been treated with at least one chemotherapy regimen in the metastatic setting experienced a significant survival benefit with T-DXd, Quiroga details. The agent improved both progression-free survival (PFS) and overall survival (OS) compared with the standard physician's choice of chemotherapy, Quiroga notes. The median PFS with T-DXd was 10.1 months vs 5.4 months with chemotherapy, while median OS was 23.9 months and 17.5 months with the respective regimens. Based on these data, the drug received FDA approval for the treatment of patients with unresectable or metastatic HER2-low breast cancer in 2022.

Overall, promising responses to T-DXd offer newfound treatment possibilities for a substantial number of patients, many of whom were previously considered to have limited therapeutic options. The recognition of HER2-low status also signals an opportunity to develop more precise, individualized therapeutic approaches through future research, Quiroga concludes.