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Test for six key genes can spot aggressive breast cancer

Breast cancer cells stained for DNA (red), NFkB (green), and a reactive oxygen species probe (blue). Julia Sero  the ICR, 2011

Breast cancer cells stained for DNA (red), NFkB (green), and a reactive oxygen species probe (blue) (photo: Julia Sero/ICR)

Testing the activity of as few as six key genes is helping to identify women with particularly aggressive breast cancer.

The research, published in the journal Clinical Cancer Research, could form the basis of future tests to direct treatment to cancers that have responded poorly to conventional therapy.

Assessing gene activity within breast cancers before and after chemotherapy is helping to highlight the role that specific genes play in drug resistance and the progression of the disease. The research is also helping to find potential targets for future treatments.

It could also help to identify women who needed especially intense treatment, or others who were likely to respond very well to initial chemotherapy and can be spared the unpleasant side-effects from further treatment.

Researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust aimed to find out what effect chemotherapy had on tumour cells — and which genes were important to test to allow doctors to make informed decisions about a patient’s treatment.

Gene activity studied

The study was funded by a range of organisations including Breast Cancer Now and the National Institute for Health Research Biomedical Research Centre at The Royal Marsden and the ICR.

It included samples from 126 patients with different types of breast cancer who had received chemotherapy to shrink their tumours before surgery.

The researchers initially looked at the activity of 24 genes that had previously been used to assess the severity of a patient’s cancer or whether treatment was failing.

The genes tested represent a number of important biological processes in a cell that are often linked to cancer’s growth and spread, including cell division, metabolism, cell death and immune response.

Gene activity was altered in most of the genes after the initial round of chemotherapy — 12 were found to be overactive and eight were either less active or turned off altogether. In 14 of the genes, activity was associated with the time it took for a patient’s cancer to relapse.

Testing only six of the genes – ACACB, CD3D, DECORIN, ESR1, MK167 and PLAU – identified women with more aggressive disease, irrespective of the subtype of breast cancer the patient suffered from.

Identifying tumour aggressiveness

Chemotherapy before surgery has become more common in the clinic in recent years because it has been shown to be as effective as chemotherapy after surgery — and in some cases it gives women the option of breast-conserving surgery.

It also gives researchers the opportunity to study the effect of chemotherapy on the primary tumour, providing new insights into the disease that could lead to new, improved breast cancer treatment regimes in future.

Study leader Professor Mitch Dowsett, Head of the Academic Department of Biochemistry and Professor of Endocrinology at the ICR and The Royal Marsden, said: “Our study aimed to work out how chemotherapy affects the biology of cancer cells, and if testing for genes involved in key biological processes could provide doctors with meaningful information on which to base future treatment decisions.

“We found that testing activity across a range of genes was able to assess whether or not women were likely to relapse, and to identify some women who might safely avoid the challenges of a second round of chemotherapy.”


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