A New Avenue In Breast Cancer Therapeutics

By Elizabeth Lamont, MD, MS, Senior Medical Director for Integrated Evidence at Medidata and Paolo Tarantino, MD, Breast Medical Oncologist at the European Institute of Oncology and Clinical Research Fellow at the Dana-Farber Cancer Institute

The FDA recently approved the first therapy targeting low levels of human epidermal growth factor receptor two (HER2), a major scientific advancement and promising news for those affected by breast cancer. This research, which was conducted as part of the DESTINY-04 clinical trial, published in the New England Journal of Medicine, and presented to a standing ovation at the June 2022 Annual Meeting of the American Society of Clinical Oncology (ASCO), could have a major impact on how we treat and understand breast cancer. HER2 is a protein that causes breast cancer cells to grow, and previously, patients were characterized as either “HER2 positive” or “HER2 negative.” However, new findings suggest that there is more nuance to HER2 since some HER2 negative patients may actually benefit from HER2-directed antibody-drug conjugates (ADCs). New classifications are being developed to acknowledge these findings, including the HER2-low (IHC 1+ or 2+/non amplified) and HER2-zero (IHC 0). HER2 low patients account for 50% or more of all metastatic breast cancer patients and are more common among patients with tumors co-expressing hormone receptors (i.e., estrogen receptors (ER) and/or progesterone receptors (PR)).

Results of the DESTINY-04 clinical trial show that even patients with low amounts of the HER2 protein on their tumor cells appear to benefit from treatment with the HER2-directed ADC trastuzumab deruxtecan (T-DXd) in the metastatic setting. This marks the entry of a promising therapeutic option for individuals with HER2 low breast cancer, including some patients who were formerly classified as having metastatic “triple negative breast cancer” (i.e., breast cancer that is ER, PR, and HER2 negative) and metastatic hormone resistant HER2 negative metastatic breast cancer. Now, a major shift in clinical practice and patient classification stands to create a wide range of opportunities and a handful of challenges in breast cancer clinical research, all of which could be aided by cutting-edge, artificial intelligence technology and advancements in biomarkers.