Dr. Prat on HER2-Enriched Subtype as Strong Predictor of HER2-Targeted Treatment

Aleix Prat, MD, PhD, head of the Department of Medical Oncology, the August Pi i Sunyer Biomedical Research Institute, discusses the results of the open-label PAMELA trial, in which the HER2-enriched subtype predicted pathologic complete response (pCR) to targeted treatment in patients with HER2-positive, hormone receptor (HR)-positive breast cancer.

HER2-positive breast cancer is defined by immunohistochemistry and fluorescence in situ hybridization, but the disease is heterogenous, Prat explains. Prior studies defined 4 intrinsic subtypes of the disease. One of them, HER2-enriched, suggests that it has the highest activation of the HER2 pathway. The prospective PAMELA trial treated 151 HER2-posiitve patients with trastuzumab (Herceptin), lapatinib (Tykerb), and endocrine therapy if the patient was also HR-positive. After 18 weeks, patients underwent surgery.

Results showed that the overall pCR rate was 30%. Among the HER2-enriched subtype, the pCR rate increased to 40.6%. In the non-enriched HER2 subgroup, the pCR rate was 10%. This shows that for patients with the HER2-enriched subtype, there is a high likelihood they will elicit a pCR with HER2-targeted agents, Prat says. This could lead to further reseach that will evaluate the activity of these patients on de-escalating treatment regimens, such as chemotherapy.