By: Kate M. O’Rourke
Extending the lifespans of patients with breast cancer with novel therapeutic interventions comes with a downside: It has made patients more susceptible to leptomeningeal carcinomatosis (LC), an increasingly prevalent secondary disease. Estimated to occur in up to 16% of patients with breast cancer, LC carries severe consequences.
“Leptomeningeal metastases are a catastrophic complication of breast cancer and lead to death in an average of 3.5 to 6 months, despite treatment,” said Adrienne Boire, MD, PhD, a neuro-oncologist at Memorial Sloan Kettering Cancer Center in New York City.
Recent research efforts are aiming to bring this disease, which Boire described as relatively understudied compared with other sites of central nervous system (CNS) metastases, out of the shadows. LC occurs when cancer cells invade the leptomeninges, or spinal fluid–filled compartments that surround the brain and spinal cord, either with or without parenchymal brain metastases.
“At present, the therapies we are using are based on creative reapplication of strategies from other sites of disease, and it is for this reason that there is a real push to understand the biology of leptomeningeal metastases,” Boire said.
The risk for leptomeningeal disease varies. Compared with ductal carcinoma, lobular carcinomas are more likely to metastasize to the meninges. Other factors further amplify a patient’s risk of developing LC.
“The risk for leptomeningeal carcinomatosis is greater with more aggressive tumors, such as triple-negative and HER2-positive [tumors], and it is also greater for patients who have very extensive bone metastases,” said Fatima Cardoso, MD, director of the breast unit of the Champalimaud Clinical Centre in Lisbon, Portugal.
Most patients with LC also have solid brain metastases. Research has demonstrated that patients who undergo resection of brain metastases are at an increased risk of leptomeningeal disease. One study showed that patients who underwent surgical resection of brain metastases before stereotactic radiosurgery were 6.5 times more likely to develop LC compared with those who underwent stereotactic radiosurgery alone.
The timing in which LC develops is also variable, ranging from a late-stage complication of gradual disease progression to something observed immediately upon the cancer becoming metastatic. Diagnosing LC is also a challenging endeavor because patients often have nonspecific symptoms, such as headaches, cognitive disorders, and potential signs of progressive focal lesions.
Much-Needed Guidance Being Offered
Oncology societies have gradually started to provide guidance to physicians on the diagnosis and treatment of LC.
The first European guidelines on LC were published in 2017 by the European Association of Neuro-Oncology and the European Society for Medical Oncology. The National Comprehensive Cancer Network includes a small section on LC in their guidelines for CNS cancers. The Society for Neuro-Oncology held its first conference on brain metastases in 2019.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.