[LUM#7] Predicting to Treat Better

[LUM Magazine] - Published on February 13, 2018 in Science and Society

Personalized medicine that identifies a person’s specific risks to better prevent and treat them: these are the promises of predictive and personalized medicine. It is a rapidly growing field that opens up new possibilities for patients, but also raises many questions…

Why do some people enjoy excellent health throughout their lives, while others—sometimes from a young age—face the ravages of illness? Regardless of lifestyle, which of course influences our health, we are not all equal when it comes to disease. The reason: genetics. A single small mutation in our DNA can be responsible for the onset of certain diseases. There’s no need to wait for the first symptoms to appear to find out for sure:“Thanks to genetic screening, we can now identify individuals with specific predispositions or risks,” explains Pascal Pujol,anoncogeneticist at Montpellier University Hospital. This is the principle behind predictive and personalized medicine.

Major medical breakthrough

This approach has revolutionized the treatment of certain cancers, such as those caused by mutations in the BRCA1 and BRCA2 genes. Women who carry these mutated genes have a much higher-than-average risk of developing cancer—a 70% probability of breast cancer and a 30% probability of ovarian cancer (“Pangenomic association study in individuals with BRCA1 mutations identifies new loci associated with breast and ovarian cancer risk”, in PLOS Genetics, 2013).“When genetic screening reveals these mutations, these patients are offered tailored monitoring: an annual MRI and surgery between the ages of 40 and 50 to remove the ovaries. Thanks to this protocol, it is estimated that we save the life of one in four women—this is a major medical breakthrough!” enthuses Pascal Pujol.

Recently, these women have also been able to receive a specific treatment that targets the genetic mutation.“Predictive medicine thus makes it possible to improve the effectiveness of treatment. We’re moving from a screening approach to a therapeutic one—it’s a true paradigm shift,” explains the president of the French Society of Predictive and Personalized Medicine (SFMPP). Already, 25,000 affected patients have been identified, but the mutation is actually much more common.“Genetic screening is only offered to those with a family history of cancer, ”notes Pascal Pujol, “whereas in one out of every two cases, the cancer occurs without any such history” (Genesis: A French National Resource for Studying the Missing Heritability of Breast Cancer, in BMC Cancer, 2016). The solution? Expand genetic screening to all women with metastatic breast cancer (Referral for Genetic Counseling and Testing in BRCA1/2 and Lynch Syndromes, in Journal of Clinical Oncology, 2013) .

When You Find What You Weren't Looking For

While genome sequencing is thus becoming increasingly popular, it also raises many questions, particularly regarding incidental findings.“In 2 to 4 percent of cases, genetic testing reveals an abnormality unrelated to the one being investigated, but one that could have serious consequences,” explains Pascal Pujol. What should be done with this information? What should—or shouldn’t—be disclosed to the patient?“For now, there are simply no regulations,” laments the specialist. In half of all cases, the laboratory does not report this finding to the physician. And when they are informed, only one in two physicians chooses to share it with the patient.“We can’t turn a blind eye; if there are life-or-death issues at stake for the patient, why sweep them under the rug?” asks Pascal Pujol (The Role of the General Practitioner in the Care of BRCA1 and BRCA2 Mutation Carriers: Perspectives of the General Practitioner and the Patient, in Molecular Genetics and Genomic Medicine, 2018) .

The specialist was thus presented with the case of a 15-year-old girl who had undergone genetic testing to investigate intellectual disability. In addition to the abnormality responsible for her developmental delay, the analysis revealed a gene that predisposes her to colorectal polyposis.“If left untreated, this condition progresses to colorectal cancer before the age of 40 in 100% of cases,” explains Pascal Pujol, who, in this instance, chose to inform the family.

On a case-by-case basis

For the oncogeneticist, the course of action must always be tailored to each individual case, systematically seeking the patient’s input through a specific informed consent process. And by taking into account the possibility of taking action:“We distinguish between treatable diseases—those where we can do something—and those that are untreatable.” The goal is to avoid unnecessarily worrying patients, but also to ensure we do not let them become seriously ill when we could have treated them.

For the president of the SFMPP, it is becoming essential to update the legislative framework while taking ethical considerations into account. “If the medical community doesn’t take the lead on this, private companies will take over predictive medicine, which will then slip out of control,” warns Pascal Pujol. Some companies are already offering a wide array of tests, conducted without any medical oversight.“Patients thus find themselves in possession of information about their genome—information that is sometimes insignificant—and they don’t know what to do with it. The public debate set to begin in 2018 and the revision of the bioethics law in 2019 will provide an excellent opportunity to reflect on these issues from both a medical and a societal perspective.”

Keywords: LUM#7, LUM Magazine, Medicine, Research, Health