Gene signature identifies patients who will respond to chemo

9 May 2009

Researchers have identified a genetic signature that can predict which breast cancer patients will respond well to treatment with epirubicin, a widely used form of chemotherapy, they reported at the IMPAKT Breast Cancer Conference in Brussels.

Finding ways to tailor therapy to the characteristics of individual patients is an important area of cancer research. The new study shows that this goal can be achieved by developing more sophisticated ways to use older drugs.

"Developing new targeted therapies is an important goal, however there are many chemotherapy drugs that we have been using for years but for which we currently have no means of telling which patients will benefit," said  study author Prof. Martine Piccart, from Institut Jules Bordet in Brussels.

"In breast cancer there are a lot of different subtypes, which are essentially different diseases. If you put them all together in the same basket and treat them the same way, you are not going to treat your patients properly."

Led by Dr Christine Desmedt from Institut Jules Bordet, researchers in Belgium, France, Luxembourg and Italy collaborated to study 149 women with breast cancer who were being treated with epirubicin, an anthracycline drug with a long history of use in many tumour types, but especially in breast cancer.

Although anthracycline drugs are among the most effective chemotherapies in breast cancer, a small proportion of women suffer severe side-effects that include congestive heart failure. By identifying those women who are most likely to benefit from treatment, doctors may be able to ensure fewer women are unnecessarily exposed to that risk.

The researchers studied the gene signatures from those women whose tumours completely disappeared in response to treatment with the drug. They identified two distinct signatures for tumours that over-expressed the HER2 gene (which tend to by more aggressive) and those which did not. Both signatures consisted of several hundred different genes expressed by the tumour cells.

Importantly, the study avoided any possible confusion by including only women being treated with single-agent doxorubicin. The researchers also limited their patient population to women whose tumours did not over-express the oestrogen receptor. This is because for these women, chemotherapy can stop the ovaries from working, offering an additional benefit that may confuse the results.

The study was made possible thanks to support from the Luxembourg Cancer Foundation, said Prof. Piccart.