Supplementary Material for: Brain metastases of a triple-negative breast cancer – A systematic literature review of the systemic treatment options

Background: The development of brain metastases (BM) is an increasing concern for patients with metastatic triple-negative breast cancer (mTNBC). This systematic review aims to summarize the current evidence regarding systemic treatment options for patients with mTNBC and BM. Methods: A systematic literature review was conducted by searching the database PubMed with the key words „metastatic triple-negative breast cancer“, ”therapy“ and “brain metastases”. Articles were screened and included if they focused on the treatment of mTNBC. Both prospective and retrospective clinical trials were eligible for inclusion. Results:The literature search identified 3,413 articles, of which eight met the inclusion criteria. These studies provided evidence for the treatment of patients with stable BM using Sacituzumab Govitecan (SG), Pembrolizumab combined with chemotherapy, Trastuzumab Deruxtecan (T-DXd), Nab-paclitaxel combined with Cisplatin, and Talazoparib. No evidence was found for active BM or leptomeningeal metastases. Conclusion: Based on the current evidence discussed in this review, testing for PD-L1, HER2, including immunohistochemistry (IHC) status as well as germline BRCA 1/2 mutation should be considered in all mTNBC patients with BM as the results have significant treatment implications.. Moreover, PD-L1 expression should be evaluated on primary tumor and (if tissue sample available) reevaluated on BMs if negative on primary BC, to maximize the opportunity for treatment with immune checkpoint inhibitors (ICI). Furthemore, if brain tissue available HER2 IHC should also be tested in order to evaluate the status switch and to assess the therapeutic effectiveness of treatment with T-DXd. Further targeted agents are urgently needed in order to improve the survival of patients with TNBC and BM