New Study Sheds Light on Breast Cancer and Leptomeningeal Metastases: What You Need to Know
Leptomeningeal metastases (LM) occur when breast cancer cells spread to the lining of the brain and spinal cord. This condition is rare but extremely serious. A new study using data from the German Brain Metastases in Breast Cancer Registry (BMBC) provides important insights into who develops LM, how it affects survival, and what treatments may help.
The study found that patients with LM have a significantly worse prognosis than those whose breast cancer spreads only to the brain itself. Several factors were linked to shorter survival, including older age, poorer physical function, and certain tumor types such as hormone receptor positive but HER2-negative tumors, or triple-negative breast cancer. However, treatments like brain radiotherapy, hormone therapy, and HER2-targeted therapy were associated with longer survival.
This study matters because patients with LM typically survive for only about six months after diagnosis, highlighting a major unmet need. Knowing which patients are at higher risk and which treatments might help can lead to better care strategies and clinical trial designs.
Researchers analyzed data from 3,857 breast cancer patients with brain involvement. Of these, 859 had leptomeningeal metastases. Some had both brain metastases and LM, while others had only LM. The data came from 113 cancer centers across Germany, collected between 2014 and 2023. LM was diagnosed either by finding cancer cells in the cerebrospinal fluid or by combining MRI results with neurological symptoms like headaches, confusion, or weakness.
Among patients with LM, the median age at diagnosis was 58 years. Many had hormone receptor-positive, HER2-negative tumors or triple-negative breast cancer. Although most patients had reasonably good physical status at diagnosis, those with LM overall had worse functioning than patients with brain metastases alone. Around 80% also had cancer spread outside the brain at the time LM was diagnosed.
When looking at survival, the study found that patients with LM had a median progression-free survival of 4.2 months and a median overall survival of 5.7 months. In comparison, patients with brain metastases but no LM had a median overall survival of 8.7 months. Only about 5.5% of LM patients survived for four years after diagnosis.
Some treatments seemed to help patients live longer. Radiation therapy to the brain, especially stereotactic radiotherapy or whole brain radiation, was associated with better outcomes. Endocrine therapy helped patients with hormone receptor-positive cancers. HER2-targeted therapies, like trastuzumab, also improved survival among patients with HER2-positive cancers. However, the study noted that HER2-targeted treatments were used less often in LM patients than in those with brain metastases alone, despite the survival benefits.
Patients had worse survival if they were older than 60 at the time of diagnosis, had worse physical function (ECOG performance status 2–4), had hormone receptor-positive but HER2-negative tumors or triple-negative breast cancer, or had multiple brain metastases at diagnosis.
Some questions remain unanswered. Intrathecal therapy, where drugs are injected into the spinal fluid, was used in a small number of patients but did not show a clear benefit for survival. Additionally, newer HER2-targeted drugs that show promise in treating brain disease, like trastuzumab deruxtecan and tucatinib, were not widely available during the study period.
This study highlights the urgent need for more clinical trials focused specifically on patients with LM. It also suggests that HER2-targeted treatments should be considered more often for appropriate patients. Further research is needed to better understand why LM develops and to find ways to treat or prevent it.
Although leptomeningeal metastases remain a serious and challenging complication for breast cancer patients, studies like this bring us closer to improving outcomes and offering hope for better treatment strategies in the future.
Want to learn more? Check this out!: Clinical characteristics and prognostic factors in patients with breast cancer and leptomeningeal metastases from a large registry of BMBC
