Breast cancer leptomeningeal metastasis (BCLM), a devastating complication of advanced breast cancer, has been the focus of a recent study that aims to enhance understanding of this condition and develop more effective treatments. Researchers from The Institute of Cancer Research, London, have made significant progress in their investigation by utilizing a novel approach that unveiled crucial details of BCLM cells. Notably, the study demonstrated that BCLM cells spread early from the primary breast tumor and acquire features commonly associated with lobular breast cancer. These insights open doors for the development of targeted treatments for individuals with progressive BCLM.
BCLM occurs when breast cancer cells spread to the leptomeninges—the protective layers of tissue lining the brain and spinal cord. It affects approximately 1 in 20 individuals with metastatic breast cancer and currently lacks effective treatment options. The rising incidence of BCLM is attributed to the fact that existing therapies prolong survival but often fail to control the disease in the brain or leptomeninges. However, little was known about the genetics or biology of this metastatic site until now, primarily due to the limited availability of biopsied samples. The challenging nature of biopsy procedures coupled with the short average survival time after diagnosis further hindered progress in studying this condition.
To overcome these limitations, researchers at the Breast Cancer Now Toby Robins Research Center at the ICR adopted a non-invasive method of obtaining material for analysis—liquid biopsies. Circulating tumor DNA (ctDNA) released by tumor cells into bodily fluids, particularly blood, provided valuable information about the cancer and its interactions within the body. By performing large-scale next-generation sequencing, covering all 20,000 genes in both plasma and cerebrospinal fluid (CSF) samples taken from patients, the study was able to compare the genetic material of leptomeningeal metastasis cells with that of the primary breast tumor and other sites of metastasis.
Significant differences were discovered between the genetic material of leptomeningeal metastasis cells and the primary tumor, illustrating the acquisition of additional mutations that could impact treatment response. Moreover, the study revealed that BCLM begins to differ genetically from the primary tumor at an early stage, emphasizing the need for tailored therapies. The research team also utilized disseminated tumor cells (DTCs) to create 3D culture models that mimic the physiological environment where the cells interact with their surroundings. These models provided a more detailed understanding of BCLM.
Furthermore, comparisons between leptomeningeal metastases and metastases in other parts of the body highlighted further evolutionary differences, with chemotherapy having a greater impact on plasma DNA than CSF DNA. The blood-brain and blood-CSF barriers were found to shield cancer cells in the leptomeninges to some extent. The study demonstrated that it is possible to investigate BCLM by using CSF DNA and DTCs, eliminating the need for invasive biopsies. The patient-derived models created by the researchers offer a valuable resource for the wider research community, providing access to cells that closely resemble those in the real clinical setting.
Looking ahead, the research team aims to identify novel drug treatments that can effectively penetrate the blood-brain and blood-CSF barriers. Current therapy options for leptomeningeal metastasis are invasive and not very effective. By developing less invasive treatment methods, such as tablets or IV infusions, researchers hope to improve outcomes for individuals with this particular form of breast cancer spread. The authors suggest that the findings of this study contribute to a deeper understanding of breast cancer metastasis to the leptomeninges, an area that has remained relatively unexplored. Through continued research and laboratory investigations, the goal is to discover better treatments for individuals diagnosed with this devastating form of breast cancer, ultimately prolonging their lives and improving their quality of life.
1. Source: Coherent Market Insights, Public sources, Desk research
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