Dr Gadi on Challenges in Identifying HER2-Low Breast Cancer in Community Settings

VK Gadi, MD, PhD, deputy director, University of Illinois Cancer Center, professor, Department of Medicine, Division of Hematology/Oncology, director, Medical Oncology, University of Illinois College of Medicine Chicago, discusses challenges associated with identifying patients with HER2-low breast cancer in community settings and the importance of open communication between pathologists and medical oncologists in the diagnostic process.
HER2 classifications have come under increased focus following results from the phase 3 DESTINY-Breast06 trial (NCT04494425) investigating treatment with fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) in patients with hormone receptor (HR)–positive, HER2-low and -ultralow breast cancer. Findings from the study demonstrated that treatment with T-DXd led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with physician’s choice of chemotherapy in patients with HER2-low disease, and data were consistent in a small subset of patients with HER2-ultralow disease. In the intention-to-treat (ITT) population, which included patients with HER2-low or -ultralow disease, the median PFS was 13.2 months with T-DXd vs 8.1 months with chemotherapy (HR, 0.63; 95% CI, 0.53-0.75; P < .0001). An improvement in PFS was also observed with T-DXd in the HER2-low group (HR, 0.62; 95% CI, 0.51-0.74; P < .0001).

The identification of HER2-low disease remains inconsistent, posing a significant challenge in clinical practice, Gadi notes. In academic medical centers, direct communication between oncologists and pathologists facilitates accurate HER2 readouts, where it is easier to ask pathologists to check for varying HER2 levels, Gadi explains.

However, in community settings, where such direct communication between oncologists and pathologists may be less frequent, identifying patients with HER2-low disease becomes more challenging, Gadi explains. Many pathologists do not routinely report HER2-low status, which can lead to missed opportunities for optimal treatment, he says. This gap underscores the need for better integration and communication between pathologists and oncologists in these settings, Gadi concludes.