Dr Hoda on Characterizing HR–Positive, HER2-Low, -Ultralow, and -Null Metastatic Breast Cancer

“We found that really a remarkable number of patients would be eligible for HER2- targeted antibody therapy. We found that [53.9% of patients had] HR-positive and HER2-low [disease]. We found that another [16.2% of patients] were HR positive and ultralow for HER2. [Therefore, 70.1%] of patients would be eligible for this [type of] therapy, which is outstanding.”

Raza Hoda, MD, FASCP, assistant professor, pathology and laboratory medicine, Cleveland Clinic Lerner College of Medicine, discusses findings from a retrospective analysis characterizing hormone receptor (HR)–positive, HER2-low, -ultralow, and -null breast carcinoma in the metastatic setting.

The study evaluated 130 metastatic breast carcinoma samples from 124 patients, with a median age of 67 years (range, 35-86). Most samples were HR positive/HER2 low (53.9%), followed by HR-positive/HER2 ultralow (16.2%) and HR-positive/HER2 null (6.1%). The majority of metastatic samples were obtained from bone (56.2%), followed by liver (18.5%), lung (7.7%), and soft tissue (6.2%).

HER2 and HR concordance between primary and metastatic tumors was assessed in 66 paired samples, with 71.2% of samples showing consistent HER2 status. However, 15.2% of HR-positive/HER2-low primary tumors had HR-positive/HER2-ultralow metastases, whereas 71.4% of HR-positive/HER2-ultralow and HR-positive/HER2-null primary tumor samples had discordant HER2 statuses in metastatic sites.

Hoda highlights that 53.9% of patients with HR-positive/HER2-low metastatic breast cancer and an additional 16.2% of patients with HER2-ultralow disease could be candidates for HER2-targeted antibody-drug conjugates (ADCs). Although guidelines from CAP and ASCO state that HER2-low and -ultralow classifications lack prognostic or predictive value, this study emphasizes the therapeutic potential of recharacterizing HER2 status in metastatic disease, particularly for identifying candidates for novel HER2-targeted therapies, according to Hoda.

The study also underscores the dynamic nature of HER2 expression, Hoda notes. Changes in HER2 status between primary and metastatic tumors indicate that retesting at disease progression may refine treatment decisions, he says.

The findings align with the growing need to integrate HER2 characterization into clinical workflows for metastatic breast cancer, Hoda explains, concluding that the study provides valuable insights into the clinicopathologic landscape of HR-positive, HER2-low, -ultralow, and -null metastatic breast cancer and supports further exploration of HER2-targeted therapies for this population.