Mafalda Oliveira, MD, PhD

Identifying new therapeutic options for a subgroup of advanced hormone receptor (HR)-positive breast cancer patients.

Impact

While hormone receptor (HR)-positive breast cancers tend to have a good prognosis and respond well to therapy, a subset of HR-positive breast cancers tend to be more aggressive. In this subtype, the HER2 gene is activated but HER2 protein (which is the target of HER2-targeted therapies) is not detected. These are therefore distinguished from HER2-postive breast cancer with the classification of HER2-enriched (HER2-E) and comprise about one in five patients with HR-positive/HER2-negative advanced disease. Clinically, these breast cancers have a poor survival rate and are resistant to both endocrine therapy and CDK4/6 inhibitors. The androgen receptor—a primary target in the treatment of prostate cancer—is present on many HR-positive breast cancers, and HER2-E tumors appear to exhibit an addiction to AR. Dr. Oliveira and her team are conducting a clinical trial in patients with HR-positive/HER2-E metastatic breast cancer to see if AR-inhibiting drugs can improve treatment response in these patients.

Progress Thus Far

The team uses the PAM50 diagnostic assay to identify patients with metastatic breast cancer whose tumors are classified as HR-positive/ HER2-E. The trial is testing if the AR-targeting drug, enzalutamide, can stop tumor cell growth in these patients after two weeks, and then patients will continue on therapy for as long as it is successful. As of the last report, 34 patients have been enrolled and the trial includes patients with HER2 enriched breast cancer, whose treatment response will be compared to those with Luminal A/B-type breast cancer.

What’s next

With recruitment now completed, data analysis is ongoing. The results of the study will be presented at the San Antonio Breast Cancer Symposium in SABCS 2023, and a manuscript is in preparation.