Activating ERBB2 (HER2) mutations can be seen in breast cancer without amplification of the gene in 1-3% of cases, but can be higher in patients who have been treated with hormonal therapy for hormone receptor-positive disease at a higher rate, perhaps 5% or even as high as 10% being reported in lob...

ERBB2 mutation is one of the upcoming new therapeutic strategies, especially in ER+ breast cancers. While only 1.6% of primary non-HER2-amplified ER+ breast cancers harbor HER2 mutations, 6-10% of all metastatic breast cancers can have HER2 mutations, suggesting their causal role in contributing to ...

Typically, a HER2+ result either by IHC and/or FISH irrespective of the site of biopsy acquisition for histologic diagnosis, dictates medical decision making. HER2 mutations are associated with accelerated internalization of the receptor (Li et al., PMID 32213539), and, to that end, I would anticipa...

I would consider treatment with T-DXd in this patient. The DESTINY-Breast04 study permitted enrollment of patients with breast cancers that were HER2-low on primary or metastatic breast cancer samples, and so this patient would have qualified for the study. The DAISY trial demonstrated that HER2 0 b...

ERBB2 mutations are different from gene amplification, hence they may not result in protein expression. There is probably tumor heterogeneity in this case. I would consider using a TKI (Neratinib, Tucatinib) at some point during the course of therapy based on efficacy data of ERBB2 TKIs in ERBB2 mut...