Gene could predict breast cancer patients' response to tamoxifen

British Journal of Cancer

Scientists have identified a gene which could help predict whether a breast cancer patient will respond to taking tamoxifen.

The study*, published in the British Journal of Cancer** today (Wednesday), showed a potential link between the activity of a gene called BCAR4 and the likelihood that a breast cancer tumour will not respond to tamoxifen – widely used to treat women with breast cancer.

Tamoxifen prevents oestrogen from stimulating growth of breast cancer cells but some tumours can eventually develop resistance to the treatment, making the drug ineffective.

The research looked into why this might happen by examining the BCAR4 gene. Using samples from 280 breast cancer patients, the researchers found that tamoxifen had a weak or limited effect on tumours with a highly active BCAR4 gene.

The study also found that the level of BCAR4 in a tumour was linked to a poor prognosis regardless of whether the patient received tamoxifen.

Dr Ton van Agthoven, lead author*** of the study, said: “We know that breast cancer cells have different ways to escape tamoxifen therapy. Now BCAR4 may be a promising target for development of new treatments.

“Preliminary results show that BCAR4 is only active in the cancer cells and not in normal adult tissues. Therefore treatments which fight against BCAR4 may have limited side effects for the patient.”

Research into the genes that control how breast cancer responds to treatment will help doctors provide patients with the most effective treatment for their tumour as early as possible, increasing their chance of survival.

It could also lead to the development of new breast cancer drugs to target tumours with a specific genetic make-up.

Scientists also speculate that testing for BCAR4 activity could reveal if a patient may benefit from drugs used to target the protein HER2, such as Herceptin. The study suggests that in the future more people might benefit from these drugs.

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “These early results tell us more about why tamoxifen can stop working for some women. We need further research into the BCAR4 gene to decide if it could lead to better ways to treat patients.

“Understanding the make-up of a tumour can enable drugs to be tailored to individual patients, and this could potentially improve cancer survival in the long term. In the future, doctors may be able to use this type of information to match the best treatment to the patients most likely to benefit and avoid giving treatment that is less likely to be effective.”

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References

**Marcia, F.E. Godinho et al., Relevance of BCAR4 in tamoxifen resistance and tumour aggressiveness of human breast cancer, British Journal of Cancer (2010)

Notes to Editor

*funded by Erasmus MC Grants

***based at the Josephine Nefkens Institute, Erasmus MC-University Medical Centre Rotterdam in The Netherlands