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Breaking through barriers

November 9th, 2016

One in eight women die from breast cancer each day, predominantly from the secondary stage of the disease (also called advanced or metastatic breast cancer). Once the cancer has progressed beyond the primary tumour site to the brain, bones, liver and lungs, the survival rate is alarmingly low and is still a major challenge for researchers.

Dr Normand Pouliot
Olivia Newton-John Cancer Wellness and Research Centre

normand-portrait

Women and men diagnosed with the aggressive HER2+ subtype of breast cancer are at high risk of developing secondary tumours (metastasis) in the brain.

Despite the introduction of HER2-targeted therapies (Herceptin) for advanced breast cancer, the incidence of patients developing secondary brain cancer is increasing.

This has been attributed in part to improved control of the disease in other organs that extends the life of patients, as well as the lack of efficacy of HER2-targeting drugs against brain metastasis due to the development of resistance and/or the drug not being able to penetrate the blood-brain barrier.

Currently, it is not possible to predict which patient will develop brain metastases because there is no routine monitoring, meaning patients are often diagnosed too late when neurological symptoms are already apparent. Although it is possible to monitor brain metastasis via MRI screening, it is expensive and therefore not implemented as routine screening.

Once brain metastasis is detected the treatment options become palliative so there is an urgent need to identify biomarkers that can predict its development to enable patients with HER2+ breast cancer who are at risk to be identified and treated earlier to improve their clinical outcome.

Dr Normand Pouliot and his team are using a unique mouse model that closely mimics the spread of HER2+ breast cancer to the brain to identify new genes that cause brain metastasis and/or that predict breast cancer spread to brain.

They aim to identify a ‘gene signature’ specific to HER2+ brain metastasis which can be used to identify high risk patients prior to the development of brain lesions. These patients could then be closely monitored, allowing for earlier detection and more effective therapeutic interventions tailored to the individual patient.

The team will also test novel combinations of therapies designed to prevent the emergence of resistance to HER2-targeting drugs and improve their efficacy against HER2+ brain metastasis.

NBCF future view:
Over the next few years a three-pronged approach is needed to reduce deaths from the metastatic stage of breast cancer. Researchers in this field will need to:

1. Understand what triggers cancer cells to travel and settle in distant parts of the body to develop ways to prevent that initial action
2. Develop the tools to know which cancers are likely to metastasise, and monitor them
3. If the cancer has already spread, be able to search out its location in the body and either destroy or control further spread.

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