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Esope Study: New Revelations on Metastatic Breast Cancers

Valérie Devillaine
Better knowledge of genomics, new treatment perspectives; Institut Curie is revealing its most recent discoveries on metastatic breast cancers at the annual AACR meeting, in Chicago (United States). These are the latest results from the important Esope clinical trial.

Anaïs Boulai on behalf of the team of Dr Paul Cottu, deputy head of the Medical Oncology Department at Institut Curie, presented new targets for personalized treatments, and the biologist Keltouma Driouch showed posters presenting new information on the genomic evolution of cancer cells from the initial tumor to its metastases in breast cancer.
The ESOPE trial, designed and coordinated by Institut Curie, was funded in 2008 as part of the Hospital Clinical Research Program. “This is an important prospective description study of metastatic diseases in breast cancer, and one of the first to look into the differences between the primitive tumor and metastases”, explains Dr Cottu. Until 2013, 125 patients with metastatic breast cancer in six centers in France, were selected to participate in the trial. Samples of their primitive tumor, in the breast, and their metastases in the liver, bone, etc., were taken to analyze their genomic details. The advantage of such a prospective study is to monitor patients and learn details about the history of their illness, their state of health, treatments used, etc.
ESOPE had three goals. The first was to draw up a clinical description of patients and histological analyses of their metastases to cover all situations: different varieties of breast cancer, different locations and appearance times (early or late metastases). This first step already revealed that the long-term prognosis for these cancers is more linked to the biology of the metastases than that of the primary tumor or than the location of the secondary tumors. Enough to inform treatment choices and refine patient data.
The second part of the study was to sequence 91 genes known to be frequently altered in breast cancers, in either the primary tumor and/or in its metastases. The speech at the AACR Congress was on this second part. Scientists found significant levels of mutations in half of the genes studied, “a very solid result, that cannot be attributed to analysis bias”, assures Dr Cottu. Some of these mutations turn up in the primary tumor but not in the metastases, or inversely, or both. Among these mutations, scientists also identified some that could be targeted by specific treatments. These results highlight the advantage of genetically profiling cancer, not only on the primary tumor, but also and above all on the metastases in order to make treatment decisions. This part of the trial also enabled these mutations to be studied statistically and correlations to be discovered; some mutations are present together and only together or, on the contrary are excluded. “A result which is not useful for patients but which enables us to better understand these cancers”, underlines Paul Cottu.
The 3rd part of Esope consisted of sequencing the whole exome of some tumors, i.e. the part of the genome that codes for protein synthesis, and therefore directly functional. This part was presented by Dr Driouch in the form of posters. Such an exhaustive study reveals previously unknown mutations and also enables the number of copies of some genes to be examined, another type of genomic mutation seen in the cancer. Once again, comparing the exome of the primary tumor and that of metastases, in the same patient, highlighted that both show the same rate of mutations, but often different mutations, more varied in the metastases and more varied when these metastases appear late in the history of the disease.
The Esope trial is highly collaborative, mobilizing clinicians, surgeons, radiologists and anatomopathologists on the medical side, and on the scientific side, the Institut Curie sequencing platform and its biologists, bio-informaticians and bio-statisticians. It demonstrates the leadership of Institut Curie in breast cancer research and in the treatment of diseases, and also the importance of cross-disciplinary collaboration preferred by the Institut.
For localized breast cancer, the chances of patient survival, ten years after diagnosis, are between 80 and 90% today, whereas the mortality of women suffering from metastatic cancers is 50% after 5 years. These are welcome results for patients, opening up new treatment perspectives, and for scientists who have finer knowledge of the genomic modifications at play in these cancers.

Copyright : Uriel Chantraine / Institut Curie