Gene Signatures Identifies Breast Cancer Patients who will Respond to Chemotherapy
Finding ways to tailor therapy to the characteristics of individual patients is an important area of cancer research. The recent results from the TOP trial, one of the clinico-genomic trials serving as a pilot trial in ACGT, shows that this goal can be achieved by developing more sophisticated ways to use older drugs.
Led by the 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.
We studied gene signatures that could identify those tumours which completely disappeared in response to treatment with the drug. We 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 predictive performance of these gene signatures was validated in an external cohort of patients also treated with pre-operative anthracyclines.
Interestingly, the TOP trial avoided any possible confusion by including only women being treated with single-agent epirubicin. We 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.
These results were presented recently as an oral presentation at the annual meeting of the American Association for Cancer Research which took place in April in Denver and at the IMPAKT breast cancer conference which took place in Brussels in May.
Christine Desmedt, Jules Bordet Institute