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Tumours with a little HER2 (IHC 1+ or 2+ without amplification), or a trace (ultralow), which older HER2 drugs ignored but Enhertu can attack.
HER2-low describes tumours with a little HER2, scored IHC 1+ or 2+ without gene amplification, and HER2-ultralow describes a trace, scored IHC 0 with faint membrane staining in a small fraction of cells. Older HER2 drugs ignored these tumours, but Trastuzumab deruxtecan can attack them, as DESTINY-Breast04 and DESTINY-Breast06 showed in HR-positive / HER2-negative breast cancer and Triple-negative breast cancer (TNBC). The result redefined what 'HER2-negative' means and put pressure on pathology to score the low end reliably, hence the links to Histopathology & immunohistochemistry, Companion diagnostics, the pairing HER2-low scoring to T-DXd and the idea on AI quantification of HER2-low. It also appears in the bottleneck on biomarker validation and the Giuseppe Curigliano entry.
Ball-and-stick model from PubChem 2D record (no 3D conformer available). PubChem record
Showing the molecule this term concerns: Trastuzumab deruxtecan.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.
Patients with hormone-receptor-positive metastatic breast cancer that has stopped responding to endocrine therapy can be offered trastuzumab deruxtecan as their first chemotherapy-type treatment if the tumour shows any HER2 staining, rather than waiting until after conventional chemotherapy. Whether to use it before or after chemotherapy is now a choice, since overall survival was not shown to differ and the drug carries a risk of lung inflammation.
Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.
The trial-grade HER2-low share for TNBC is about a third, and the survival difference hints that HER2-zero triple-negative disease is the more aggressive group.
HER2-low is a drug eligibility label, not a biological subtype, in triple-negative disease; because a third of patients qualify for trastuzumab deruxtecan on a score pathologists disagree about, re-scoring and digital assistance for HER2 0 versus 1+ is a practical gap.
Shares Overexpression, Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status, Re-test the metastasis, not the old primary, before every change of treatment, Calibrated reference slides so every lab scores HER2-low the same way.
Shares HER2 IHC 1+, HER2 IHC 0 (HER2-negative, including ultralow), HER2-ultralow (IHC 0 with membrane staining), HER2 IHC 2+ (equivocal, reflex to ISH).
Shares ER and PR negative under 1 percent (the triple-negative threshold, and ER-low), HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP, Receptor conversion: when the receptors change between the primary and a recurrence, Breast cancer (all types).
Shares DESTINY-Breast04, DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group, Trastuzumab deruxtecan, HER2.
Shares HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP, HER2 IHC 2+ (equivocal, reflex to ISH), HER2-low (IHC 1+ or IHC 2+/ISH-negative), HER2-positive (IHC 3+ or ISH-amplified).
Shares Receptor conversion: when the receptors change between the primary and a recurrence, HER2-positive (IHC 3+ or ISH-amplified), Histopathology & immunohistochemistry, Breast cancer (all types).
Shares DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer, DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group, Trastuzumab deruxtecan, HER2.
Shares Overexpression, HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease), TROP2 expression, A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer.