https://orcid.org/0000-0002-4106-409X
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ABSTRACT
Introduction
Neoplastic meningitis (NM), also known as leptomeningeal carcinomatosis, is characterized by the infiltration of tumor cells into the meninges, and poses a significant therapeutic challenge owing to its aggressive nature and limited treatment options. Breast cancer is a common cause of NM among solid tumors, further highlighting the urgent need to explore effective therapeutic strategies. This review aims to provide insights into the evolving landscape of NM therapy in breast cancer by collating existing research, evaluating current treatments, and identifying potential emerging therapeutic options.
Areas covered
This review explores the clinical features, therapeutic strategies, recent advances, and challenges of managing NM in patients with breast cancer. Its management includes multimodal strategies, including systemic and intrathecal chemotherapy, radiation therapy, and supportive care. This review also emphasizes targeted drug options and optimal drug concentrations, and discusses emerging therapies. Additionally, it highlights the variability in treatment outcomes and the potential of combination regimens to effectively manage NM in breast cancer.
Expert opinion
Challenges in treating NM include debates over clinical trial end points and the management of adverse effects. Drug resistance and low response rates are significant hurdles, particularly inHER2-negative breast cancer. The development of more precise and cost-effective medications with improved selectivity is crucial. Additionally, global efforts are needed for infrastructure development and cancer control considering the diverse nature of the disease.
Abbreviations
| PFS | = | Progression free survival |
| JAK | = | Janus Kinase |
| MTD | = | Maximum Tolerated Dose |
| ORR | = | Objective Response Rate |
| AE | = | Adverse Events |
| DFS | = | Disease Free Survival |
| DLT | = | Dose Limiting Toxicity |
| MTX | = | Methotrexate |
| NM | = | Neoplastic meningitis |
| LM | = | Leptomeningeal metastasis |
| BC | = | Breast cancer |
| CNS | = | Central Nervous System |
| CSF | = | Cerebrospinal fluid |
| HDMTX | = | High-dose methotrexate |
| OS | = | Overall survival |
| IT | = | Intrathecal chemotherapy |
| RT | = | Radiation therapy |
| SC | = | Systemic chemotherapy |
| MTX | = | Methotrexate |
| IT Mtx | = | intrathecal methotrexate |
| TNBC | = | Triple-Negative Breast Cancer |
| BBB | = | Blood Brain Barrier |
| RT | = | Radiotherapy |
| LP | = | Lumbar puncture |
| WBRT | = | Whole-brain radiation therapy |
| SRS | = | Stereotactic radiosurgery |
| SRT | = | Stereotactic radiotherapy |
Declaration of interest
MS Ahluwalia has received grants from Seagen and has consulted for Bayer, Novocure, Kiyatec, Insightec, GlaxoSmithKline, Xoft, Nuvation, Cellularity, SDP Oncology, Apollomics, Prelude, Janssen, Tocagen, Voyager Therapeutics, Viewray, Caris Lifesciences, Pyramid Biosciences, Varian Medical Systems, Cairn Therapeutics, Anheart Therapeutics, Theraguix, Menarini Ricerche, Sumitomo Pharma Oncology, Autem therapeutics, and GT Medical Technologies. M. S. Ahluwalia is also on Scientific Advisory Boards for Cairn Therapeutics, Pyramid Biosciences, Modifi Biosciences, and Bugworks and is a stock/shareholder with Mimivax, Cytodyn, MedInnovate Advisors LLC, and Trisalus Life Sciences. R Mahtani serves as a consultant/advisor for AstraZeneca, Daiichi Sankyo, Eisai, Genentech, Gilead Sciences, Hologic, Eli Lilly and Company, Merck and Co, Novartis, Pfizer, Puma, Sanofi, Seagen Inc, Sermonix and Stemline. All other authors have no relevant conflicts of interest to declare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.