Scientific breakthroughs in 2019: a step ahead of cancer

“The basic idea is that the sooner we detect breast cancer, the better the chances of survival. That’s why we have a mammography program for women aged 50 to 69. Except that almost one in five cases of breast cancer (18%) is diagnosed before the age of 50, so before these women become eligible for the mammography program. So how do we identify those women who are most at risk so that they too can benefit from mammography? ”
Jacques Simard, a specialist in cancer genetics from the Research Center of the CHU de Québec, has been working on this thorny question for more than 20 years. And last January, he and a few dozen of his colleagues around the world published two articles that, in essence, sum up everything we know about risk factors (genetic or otherwise) for breast cancer, in scholarly journals Genetics in Medicine and the American Journal of Human Genetics.

The question was not easy. We knew of course the infamous BRCA1 and BRCA2 genes, which are part of a handful of “genes” (not even half a dozen) that multiply the risk of breast cancer by 5 or 6 during a lifetime. But these genes are not very frequent, being present in approximately one woman in 200, and are therefore very insufficient to understand the genetic risk of women in general. In this regard, there were also known just over 170 locations in the genome that are linked to this cancer and that are much more common in the population, but each of them makes only a minimal difference. And we knew that there were still quite a few other genes involved to discover since these 170 locations explained only about 40% of the heritability of this cancer.

Mr. Simard and his colleagues therefore first sequenced the genome of no less than 94,000 women who were diagnosed with breast cancer and 75,000 women who never had one, looking for small ” mutations ”called SNPs (from the English single nucleotide polymorphisms). And they were able to identify 313 that played a role in breast cancer one way or the other – some increased the risk, but others had a protective effect.

Statistical model

Putting it all together, they got the most accurate “genetic risk scores” ever developed so far. In this statistical model, women in the 1% most at risk are about 3.5 times more likely than the average to develop a breast tumor in their lifetime, while the “lucky ones” who have inherited enough protective genes to be in the 1% least likely, they run a risk about 4 times less than the average. This is the book that appeared in the American Journal of Human Genetics.

From there, Mr. Simard and others of his colleagues integrated this new data into a more general model called BOADICEA which, in addition to genes, also takes into account family history, lifestyle, etc. “It is the culmination of a long progression which took almost 20 years. It’s a model that was developed by my colleagues at Cambridge, says Simard. […] At first, it was a tool used by oncogenetics clinics, which was made for women who were at high risk because of their family history. Here we have just taken a major step and it is becoming a population screening tool for all women. ”

Stratify the risk

This model too, published in Genetics in Medicine, makes it possible to “stratify” the risk, that is to say to distinguish women at high risk from those who are unlikely to develop a tumor in a breast. “If we just take the epidemiological questionnaires [Editor’s note: on family history and lifestyle], that places 66% of women in the“ moderate risk ”category and 1.8% in high risk [Editor’s note: the balance 32.2% with low risk]. But with the complete model, it is 36.6% who have a moderate risk and 9.8% who are at high risk [and therefore more than half, 53.6%, who are low risk ”, which identifies the women most at risk much more precisely, says Simard.

With this information in hand, the researchers hope that breast cancer screening programs will be able to better target their “clientele”. This could possibly mean, for example, extending the Quebec mammography program to certain women under the age of 50 who are more vulnerable to breast cancer – but it will be up to political decision-makers to decide, “We are just giving them information, ”says Simard. Conversely, he adds, “there is also a fairly large proportion of women, between 10 and 15%, who have a much lower risk than the average. So could their doctors talk to them about having a mammogram every 2 or 3 years instead of doing it every year? This is a question that may arise. ”

The researcher at the CHU de Québec is also in the process of finalizing a new research project that will be used to test this new model with real patients. “Does this allow us to detect breast cancer earlier, at a earlier stage of development?” This is really the objective of this project, to see if the model works […] and if it is well received by patients, ”he says.

In an interview in early December, Mr. Simard said he was finalizing the pilot study and preparing to recruit patients from 40 to 69. “It is in the Quebec region and in the Lanaudière region. They just have to go to the website. […] Recruitment should start around the beginning of February. ”

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