Low level limbo in HER2 breast cancer
August 2023—Seemingly channeling the inspiration of Magritte and his famous pipe, pathologists are painting a new picture of what has long been an everyday object in their own world: HER2. To paraphrase the master: Ceci n’est pas facile. For years, HER2 testing in breast cancer has seemed self-evident, ever since the HER2-targeted therapy trastuzumab and its companion diagnostic arrived on the scene a quarter of a century ago. Pathologists became comfortable using immunohistochemistry to identify 3+ cases and turning to in situ hybridization techniques to sort through less obvious ones. But early last summer, a variant of the drug, trastuzumab-deruxtecan (T-DXd), shook up that routine. When researchers presented results from the Destiny-Breast04 study at the 2022 ASCO annual meeting, showing that T-DXd significantly improves survival in so-called HER2-low metastatic breast cancer, attendees responded with a minutes-long standing ovation. They then returned from the meeting like evangelicals from the revival tent.