ERBB2 V842I is a mutation identified in breast cancer patients, located within the kinase domain, which increases kinase activity, in vitro, and increases the number of colonies formed in soft agar. Cells with this mutation display an invasive morphology, but tumor xenografts formed from these cells do not grow more rapidly than those with wild-type HER2. When assessing sensitization to HER2-targeted therapies in vitro, cells with this mutation are highly sensitive to neratinib but less sensitive to lapatinib, in a manner similar to wild-type HER2.

The ERBB2 p.V842I mutation has been previously reported in several cancer types and has been reported to be an activating mutation. The potential for these mutations to be used for selection of patients to targeted therapies continues to be evaluated.