Discovery lights the way for new secondary breast cancer drugs

Breast cancer cell

Using a novel approach, researchers from The Institute of Cancer Research, London have uncovered details of secondary breast cancer in the brain and spinal cord that may help with developing effective treatments.

The study revealed for the first time that breast cancer leptomeningeal metastasis (BCLM) cells spread early from the primary breast tumour and that they acquire features typically associated with lobular breast cancer, which develops in the glands that produce breast milk.

The researchers implanted BCLM cells from five patients into mice to establish models of the disease that other researchers can use.

BCLM occurs when breast cancer cells spread to the leptomeninges – the two layers of tissue lining the brain and spinal cord. It is estimated to affect one in 20 people with metastatic breast cancer, and there is currently no effective treatment.

Relatively little has been known about the genetics or biology of this metastatic site until now. The site is rarely biopsied due to the short average survival following diagnosis and the difficulty of accessing the leptomeninges.

BCLM genetically distinct from primary breast tumour

For this study, researchers at the Breast Cancer Now Toby Robins Research Centre at the ICR analysed liquid biopsies, which contain circulating tumour DNA (ctDNA).

The study was the first to perform large-scale (whole exome) next-generation sequencing covering all 20,000 genes in both plasma and cerebrospinal fluid (CSF) from the same patient. In addition, tissues from the original breast cancer tumour and from other sites to where the cancer had spread were sequenced.

Comparisons between the samples revealed that the leptomeningeal metastasis cells had acquired additional mutations, including some that could affect the response to treatment. As a result, the BCLM genetic material was clearly distinct from that of the primary breast tumour.

The next stage of this research aims to identify novel drug treatments, ideally those that penetrate the blood-brain and blood-CSF barriers, and are less invasive than current therapy.

Lead author Professor Clare Isacke, Professor of Cell Molecular Biology and Dean of Academic and Research Affairs at the ICR, said: “This work has achieved significant insights into breast cancer metastasis to the leptomeninges, which has been relatively unstudied to date. We hope that our models and discoveries serve as valuable resources for other researchers in this area. In time, with more lab research, we are optimistic that we will be able to discover better treatments for people with this type of breast cancer spread.”

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