{"entity":{"id":"her2-low-to-tdxd","kind":"pairing","name":"HER2-low scoring → T-DXd","aka":[],"tldr":"Reading the faint end of the HER2 stain decides who gets Enhertu.","summary":"This diagnostic-therapeutic pairing links Histopathology & immunohistochemistry scoring of HER2 to treatment with Trastuzumab deruxtecan (T-DXd): reading the faint end of the HER2 stain decides who gets Enhertu. The rationale is that the bystander payload needs only minimal antigen for uptake, so the immunohistochemistry cut-off is a delivery threshold rather than a driver threshold. In the phase 3 DESTINY-Breast04 and DESTINY-Breast06 trials, HER2-low (IHC 1+ or 2+) and HER2-ultralow (IHC 0 with faint staining) tumours predicted T-DXd benefit in HR-positive / HER2-negative breast cancer and Triple-negative breast cancer (TNBC). Reproducibility at the low end is poor, so AI-assisted HER2 scoring is being validated, as pursued in the idea AI quantification of HER2-low and HER2-ultralow.","asOf":"2026-09-04","links":[{"label":"ClinicalTrials.gov NCT03734029: DESTINY-Breast04","url":"https://clinicaltrials.gov/study/NCT03734029"},{"label":"ClinicalTrials.gov NCT04494425: DESTINY-Breast06","url":"https://clinicaltrials.gov/study/NCT04494425"}],"tags":[],"related":[],"cancers":["breast-hr-positive","tnbc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["her2-low"],"trials":["destiny-breast04","destiny-breast06"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"histopathology-ihc","b":"trastuzumab-deruxtecan","rationale":"Bystander payload needs only minimal antigen for uptake; IHC cut-off is a delivery threshold not a driver threshold.","evidence":"Phase 3 (DESTINY-Breast04/06).","pairingType":"diagnostic-therapeutic"},"route":"/pairings/her2-low-to-tdxd/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"term":[{"id":"her2-low","kind":"term","name":"HER2-low and HER2-ultralow","route":"/terms/her2-low/"}],"trial":[{"id":"destiny-breast04","kind":"trial","name":"DESTINY-Breast04","route":"/trials/destiny-breast04/"},{"id":"destiny-breast06","kind":"trial","name":"DESTINY-Breast06","route":"/trials/destiny-breast06/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"drug":[{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"idea":[{"id":"idea-ai-her2-low-scoring","kind":"idea","name":"AI quantification of HER2-low and HER2-ultralow","route":"/ideas/idea-ai-her2-low-scoring/"}]}}