HER2-positive breast cancer in patients with BRCA1/2 pathogenic variants: Case series and literature review

Research purpose

HER2-positive breast cancers are uncommonly reported in patients with BRCA1/2 pathogenic variants. The purpose of this case series is to describe three patients with BRCA1/2 pathogenic variants who developed HER2-positive breast cancers and their treatment courses along with that of a patient from a previously published case report, and describe existing literature exploring associations between HER2-positive breast cancers and germline variants.

Key findings

HER2-positive breast cancer is uncommon in patients with BRCA1/2 pathogenic variants. The patients in our case series had hormone receptor positive and HER2-positive breast cancers. HER2 FISH was commonly utilized for the confirmation of HER2 status in our case series. All patients responded well to HER-2 directed therapies.

Conclusions & clinical implications

While the interactions between BRCA1/2 pathogenic variants and the HER2 pathway are unclear, our case series and existing literature suggest that HER2-positive breast cancer occurrence is mainly HER2 oncogenic pathway driven. But the interplay between the DNA repair pathway and the HER2 oncogenic pathway could impact HER2 gene expression and play a potentially important role in treatment resistance and therapy options. Combining olaparib and trastuzumab could be considered for off-label use in patients with BRCA 1/2 mutations with HER2-positive breast cancer who failed HER2-targeted therapy.

Limitations

This study is limited by small sample size (n = 4). Since it is a retrospective study, it is also limited by selection bias, lack of control group for comparison purposes, and potential influence of confounding variables.