Dr Elkhanany on Biological Drivers of Progression in ER+ Metastatic Breast Cancer

Ahmed Elkhanany, MD, assistant professor, medicine, Division of Hematology & Oncology, School of Medicine, associate scientist, O’Neal Comprehensive Cancer Center, associate scientist, Center for Clinical and Translational Science, The University of Alabama at Birmingham, discusses biological drivers of disease in patients with estrogen receptor (ER)–positive breast cancer who have disease progression shortly after initiating first-line therapy, as well as the importance of performing comprehensive genetic testing in these patients to determine subsequent treatment approaches. 

When patients with ER-positive metastatic breast cancer experience disease progression shortly after starting first-line therapy, the next step in their treatment is to determine the biological driver behind this early progression, Elkhanany says. Some of these known drivers include CCND1 amplifications, which can cause resistance to CDK4/6 inhibitors, as well as ESR1 mutations and PIK3CAmutations, Elkhanany explains. Other less actionable drivers include TP53 mutations, which, though rare in ER-positive breast cancer, do occur, according to Elkhanany. It is also important to test for rare yet actionable drivers such as NTRK fusions, many of which have FDA-approved therapies, Elkhanany notes. For instance, entrectinib (Rozlytrek) is approved in patients with solid tumors harboring NTRK fusions who have metastatic disease or a known acquired resistance mutation.

Since ER-positive metastatic breast cancer is a heterogeneous disease, genomic testing is necessary to try to identify actionable mutations that are driving primary resistance in patients who progress on their frontline therapies and determine potentially effective targeted therapies for these patients, Elkhanany emphasizes. This testing is typically conducted through tissue or liquid biopsy. Although liquid biopsy can reveal a holistic view of a patient’s actionable mutations across different metastatic foci, it may not detect mutations with low allele ratios, Elkhanany says. Performing both liquid and tissue biopsy in the same patient can provide a clearer and more comprehensive assessment of that patient’s genomic profile, Elkhanany concludes.