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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
HER2-low is not a new kind of breast cancer but a new way of reading an old test: tumours once called HER2-negative that carry a little HER2 protein. That trace is enough for the antibody-drug conjugate trastuzumab deruxtecan to deliver its chemotherapy payload, and since 2022 it has been the standard for these patients after endocrine therapy or a first chemotherapy.
HER2 status was binary for two decades: 3+ by immunohistochemistry or amplified by in situ hybridisation meant trastuzumab, anything less meant nothing. Trastuzumab deruxtecan changed that because its payload, a topoisomerase I inhibitor carried eight to an antibody with a cleavable linker, is released inside the cell and diffuses into neighbours, so tumours with only a few receptors per cell still respond. HER2-low is defined as 1+ or 2+ without amplification, and HER2-ultralow as a score of 0 with membrane staining in 10 percent of cells or fewer; the 2023 ASCO and CAP testing update recognised the categories, and because expression varies between the primary and metastases and between blocks, retesting a metastatic biopsy is recommended before ruling a patient out.
DESTINY-Breast04 randomised 557 patients with HER2-low metastatic breast cancer after one or two chemotherapy lines to trastuzumab deruxtecan or the physician's choice of chemotherapy. In the hormone receptor-positive cohort progression-free survival rose from 5.4 to 10.1 months (hazard ratio 0.51) and overall survival from 17.5 to 23.9 months (hazard ratio 0.64), with the small hormone receptor-negative cohort pointing the same way. Adjudicated interstitial lung disease occurred in about 12 percent and was fatal in under one percent, and the FDA approved the indication in August 2022, the first time a HER2-directed drug had been licensed for HER2-negative disease.
| Setting | Approach | Guideline |
|---|---|---|
| Hormone receptor-positive, after endocrine therapy, chemotherapy-naive | Trastuzumab deruxtecan ahead of chemotherapy for HER2-low or ultralow disease (DESTINY-Breast06). | not mapped |
| After one or two lines of chemotherapy | Trastuzumab deruxtecan for HER2-low disease of either hormone receptor status (DESTINY-Breast04). | not mapped |
| Triple-negative HER2-low disease | TROP2 antibody-drug conjugates first (ASCENT, TROPION-Breast02), trastuzumab deruxtecan as a later option. | not mapped |
| Lung toxicity | Baseline and interval CT, prompt corticosteroids and permanent discontinuation for grade 2 or higher interstitial lung disease. | not mapped |