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Wales Cancer Research Centre,
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University Hospital of Wales,
Cardiff, CF14 4XN
4 Jan

New hope for drug resistant breast cancer

Breast cancer ribbon

Around 70% of breast cancer patients are diagnosed with oestrogen-receptor positive disease, where their breast tumours are sensitive to the fluctuating levels of oestrogen in the body. Oestrogen receptor positive breast tumour cells become ‘addicted’ to the oestrogen, replicating uncontrollably. This increases the tumour size, and potentially promotes the spread of tumour cells to other parts of the body.

Treatment of this kind of breast cancer can be very effective. Anti-hormone receptor drugs such as tamoxifen and fulvestrant block the effects of oestrogen on these tumours, and have significantly improved the survival rates of breast cancer patients. However, around half of patients receiving these therapies will, ultimately, become resistant to these drugs and may relapse with secondary breast cancers, which may be more aggressive and unresponsive to further anti-hormone therapy.

While it may take many years for these tumours to acquire this resistance, once acquired the treatment options for relapsed patients are relatively limited and often involves aggressive chemotherapy. It is recognised therefore that there is a clear need for new targeted therapies for this at-risk patient group.

Targeted therapies are ‘designer treatments’ that are aimed at very specific abnormalities within cancers – that may only be present in a small subset of cancer patients, but are highly effective at treating their disease.

A recent laboratory study from a research group at Cardiff University, reported in the international cancer journal Clinical Cancer Research has identified an “Achilles heel” in breast tumours that had previously acquired resistance to the drug tamoxifen.

Patients attending the Cardiff and Vale Breast Clinic in Llandough donated samples of their cancer to the Wales Cancer Bank, an organisation we work very closely with. The research group led by Dr Richard Clarkson used these samples to show that 85% of patients who had developed resistance to tamoxifen went on to develop a sensitivity to an unrelated experimental drug, TRAIL.

Dr Luke Piggott, the lead investigator on the study, said: “TRAIL is currently not used to treat breast cancer as most breast cancer patients are resistant to it. However, our findings suggest that it could be prescribed for the minority of breast cancer patients who re-present with breast cancer after tamoxifen therapy.”

A key finding of this study is that TRAIL is particularly effective at killing the cancer stem cells within these tumours. This means that successful treatment would prevent further relapse and therefore could significantly improve disease-free survival.

“The next step is to test TRAIL in clinical trials,” Luke explains. “We hope to lead these trials out of breast clinics across Wales, targeting patients with recurrent disease. We will work closely with the Wales Cancer Bank during these trials to ensure that we maximize the information on the effects of TRAIL in these selected patients.”

The Wales Cancer Bank’s ongoing mission is to facilitate basic, translational and clinical cancer research such as this, helping to provide improved outcomes for cancer patients across Wales and beyond.