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Test reveals which breast cancer patients may benefit from targeted therapy

Pathology slides (Jan Chlebik for the ICR, 2011)

A new test could indicate which women with some breast cancer types are likely to benefit from targeted treatments, according to new research.

The test, developed by a team from The Institute of Cancer Research, London, involves staining samples from a tumour and examining it under a microscope for traces of a protein called CDK12.

It could help doctors to work out which women might benefit from drugs that target the DNA damage response in cancer cells, such as PARP inhibitors.

In particular, the test could help direct treatment for women with triple-negative breast cancer, which does not respond to traditional hormone-based treatments.

DNA repair regulator

Writing in the journal Molecular Cancer Therapeutics, the researchers explained why they chose to develop a test for CDK12.

The protein helps to regulate the transcription of DNA repair genes, which mend defects in DNA that left unchecked can cause damage to the cells and promote cancer.

Previous research by the team showed that loss of CDK12 can lead to defects in the way cancer cells repair their DNA that could leave them vulnerable to PARP inhibitors, and to platinum-based chemotherapy drugs such as cisplatin.

Researchers at The Breast Cancer Now Toby Robins Research Centre lead important study programmes to understand the genetic and environmental causes of breast cancer.

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Tumours may be vulnerable to targeted drugs

This study, which was funded by Breast Cancer Now, set out to discover how common the loss of CDK12 was among patients with breast cancer, and whether it correlated with certain disease sub-types.

Testing tumours from women with breast cancer, the research team found that 11 per cent lacked CDK12 in their tumours – but that this rose to 17 per cent among patients with triple-negative breast cancer.

The researchers also discovered that tumours that lacked CDK12 also had reduced levels of DNA repair proteins, suggesting vulnerability to targeted drugs.

In addition, the study suggested HER2 positive breast tumours – a common type that generally has high CDK12 levels – may also be vulnerable to DNA repair-targeting drugs as a small number of these patients also lack CDK12 protein expression.

Enabling patient stratification

Dr Rachael Natrajan, who leads the Functional Genomics team at the ICR and led this study, said:

“With this study, we aimed to see if we could assess CDK12 levels – using a technique called immunohistochemistry – in breast cancer as a proxy for working out which patients may benefit from targeted drugs or platinum-based chemotherapy.

“Our research suggests that testing for CDK12 levels does indeed give us clues about which women might respond to these drugs, particularly for triple-negative breast cancer.

“It shows that testing for CDK12 could be a useful tool for stratifying patients for targeted therapies in the future.”


breast cancer Breast Cancer Now Rachael Natrajan
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