Loading
Created a new category of breast cancer, HER2-low, by showing Enhertu works in tumours previously called HER2-negative.
DESTINY-Breast04, trial NCT03734029 sponsored by Daiichi Sankyo and AstraZeneca and published in the New England Journal of Medicine in 2022, created a new category of breast cancer, HER2-low, by showing that trastuzumab deruxtecan works in tumours previously called HER2-negative after chemotherapy. It randomised 557 patients to trastuzumab deruxtecan or chemotherapy, met its primary progression-free survival endpoint in the HR-positive cohort and showed an overall survival benefit in all patients, with an exploratory HR-negative cohort pointing the same way, and it drew a standing ovation at ASCO 2022 as roughly half of all breast cancers became eligible for a HER2-directed drug. Whether pathologists can score HER2-low reproducibly is the open question.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
557 enrolled.
Exploratory cohort
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survival, HR+ cohort (BICR)primary | Trastuzumab deruxtecan | 331 | 10.1 months | 0.51 (0.4 to 0.64) | <0.001 | link |
| Chemotherapy (TPC) | 163 | 5.4 months | ||||
| Overall survival, all patients | Trastuzumab deruxtecan | 373 | 23.4 months | 0.64 (0.49 to 0.84) | 0.001 | link |
| Chemotherapy (TPC) | 184 | 16.8 months | ||||
| Progression-free survival, HR-negative (TNBC) cohort | Trastuzumab deruxtecan | 40 | 8.5 months | 0.46 (0.24 to 0.89) | - | link |
| Chemotherapy (TPC) | 18 | 2.9 months |
A second publication from the DESTINY-Breast04 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
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.
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 HER2-low scoring → T-DXd, Calibrated reference slides so every lab scores HER2-low the same way, AI quantification of HER2-low and HER2-ultralow, HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH).
Shares HER2-low eligibility for trastuzumab deruxtecan, and TROP2 ADCs without a test (triple-negative disease), Palliation in advanced triple-negative breast cancer: brain, bone, pleura, skin and end of life, TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line, A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer.
Shares Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer, Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan, HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2-low and HER2-ultralow metastatic breast cancer.
Shares AI quantification of HER2-low and HER2-ultralow, HER2-low and HER2-ultralow metastatic breast cancer, Daiichi Sankyo, Trastuzumab deruxtecan.
Shares TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line, A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer, HER2-low and HER2-ultralow metastatic breast cancer, Daiichi Sankyo.
Shares Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer, HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group, HER2-low and HER2-ultralow metastatic breast cancer.
Shares Calibrated reference slides so every lab scores HER2-low the same way, HER2-low and HER2-ultralow metastatic breast cancer, HER2-low and HER2-ultralow, Daiichi Sankyo.
Shares TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line, A randomised trial of antibody-drug conjugate sequence in metastatic triple-negative breast cancer, ADC roadmap: from Mylotarg to bispecific and dual-payload ADCs, Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem.