ERBB2 mutations linked to longer T-DXd disease control in metastatic breast cancer
Published in Diseases!, Journals, Personalized medicine.
Published October 11, 2026.
An October 9 research update from Memorial Sloan Kettering highlights evidence that ERBB2 mutations may help identify metastatic breast cancers particularly sensitive to trastuzumab deruxtecan (T-DXd). The study was published online in Clinical Cancer Research on September 9, 2026.
Researchers examined 272 patients treated with T-DXd for HER2-nonamplified metastatic breast cancer. Twenty patients, or 7.3%, had ERBB2 mutations. Their median real-world progression-free survival was 11 months, compared with 6.2 months in patients without these mutations.
The association remained after adjustment for age, treatment line, estrogen-receptor status and HER2 immunohistochemistry. Laboratory models expressing activating ERBB2 mutations internalized T-DXd more rapidly and were more sensitive to its effects than models expressing wild-type HER2.
This suggests tumor sequencing could provide information beyond HER2 protein staining. However, the clinical comparison was observational, with a small mutation-positive group. It does not establish that mutation status causes better outcomes, nor demonstrate a change in overall survival or justify extending treatment eligibility by itself.
Sources: Clinical Cancer Research study, September 9, 2026; MSK update, October 9, 2026.