HER2-low and HER2-ultralow
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: IHC 1+ or 2+/ISH-negative (~50% of breast cancers, ~35% of TNBC). HER2-ultralow: IHC 0 with membrane staining in ≤10% of cells. DESTINY-Breast04 and -06 showed T-DXd benefit in both, redefining 'HER2-negative' and putting pressure on pathology to score the low end reliably.
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.
Pages like this
not linked directly; found by shared links- TermImmunohistochemistry (IHC)
Shares Calibrated reference slides so every lab scores HER2-low the same way, Re-test the metastasis, not the old primary, before every change of treatment, Overexpression, HER2-positive (IHC 3+ or ISH-amplified).
- IdeaPublish each laboratory's biomarker proficiency results
Shares Calibrated reference slides so every lab scores HER2-low the same way, Companion diagnostics, Histopathology & immunohistochemistry, Biomarkers are not validated or standardised.
- PersonJoohyuk Sohn
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, HR-positive / HER2-negative breast cancer.
- TermHormone receptor status (ER / PR)
Shares HER2-positive (IHC 3+ or ISH-amplified), Histopathology & immunohistochemistry, Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer.
- PersonSeock-Ah Im
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, Triple-negative breast cancer (TNBC), HR-positive / HER2-negative breast cancer.
- PersonKan Yonemori
Shares DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer, Trastuzumab deruxtecan, HR-positive / HER2-negative breast cancer.
- IdeaA fund for prospective validation of academic biomarkers and companion diagnostics
Shares AI quantification of HER2-low and HER2-ultralow, Companion diagnostics, Biomarkers are not validated or standardised.
- IdeaDrug labels must state which biomarker assays were validated and how they compare
Shares Companion diagnostics, Knowledge reaches practice too slowly, Biomarkers are not validated or standardised.