Abstract
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.
Original language | English (US) |
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Article number | 100335 |
Journal | Current Problems in Cancer: Case Reports |
Volume | 17 |
DOIs | |
State | Published - Mar 2025 |
Keywords
- BRCA1
- BRCA2
- Breast cancer
- Case report
- Case series
- HER2-positive
ASJC Scopus subject areas
- Oncology