It’s not just the “Jolie mutations”. Other genes, if mutated, can increase the hereditary risk of breast cancer. And among these, from today, there is also the CDH1 gene. The discovery, entirely Italian, bears the signature of researchers from the European Institute of Oncology in Milan, authors of one studio recently published on Jama Network Open. According to scholars, on all women with a particular type of breast cancer – the lobular one (which represents around 20% of cases) – and under the age of 45, or with a positive family history of breast cancer lobular or with bilateral lobular tumors should be tested for mutations in the CDH1 gene.
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From suspicion to confirmation
Researchers define it as a new form of cancer, or syndrome, called “hereditary lobular breast cancer” associated with the CDH1 gene. “Obviously discoveries like these don’t happen overnight – specifies a Salute Of Giovanni Corso, breast surgeon at the European Institute of Oncology and researcher at the University of Milan, first author of the paper – The first suspicions that this gene – already known for the predisposition of hereditary gastric cancer – could also be associated with lobular breast cancer date back to over 10 years ago. In 2016 I won a project from the Ministry of Health to set up a large study at the IEO that could test the hypothesis”.
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I study
5,400 women with lobular cancer were enrolled in the study. Of these, 394 with the “suspicious” phenotype (very young, with bilateral cancer or with a family history) were tested for the CDH1, BRCA1 and BRCA2 genes. And the results confirmed that intuition: approximately 5% had a variant of the CDH1 gene, without mutations in the BRCA1 and 2 genes. Although it is an uncommon syndrome, the probability that this variant is pathogenic (i.e. can cause the disease) is very high, around 40%. “We are talking about a mutation that is fortunately quite rare, but very aggressive, because it is associated with tumors that appear early, even more so than those associated with BRCA mutations,” underlines Corso.
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Identify carriers of the mutation
It is therefore important to identify the carriers of this mutation, also because the lobular tumor is “more difficult” to see with normal mammography and ultrasound, and it is often necessary to resort to magnetic resonance imaging. “The opportunity for bilateral mastectomy in carriers of the mutation can be seriously considered on a case-by-case basis – says the researcher – Furthermore, it should not be forgotten that mutations in this gene are also linked to an increase in gastric cancer. We do not yet know why they are associated only with these two tumors, and the risk of also developing gastric cancer remains uncertain. But it is still possible, so annual gastroscopy is strongly recommended. The CDH1 test is therefore very important for both the woman and her family.”
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To date, the national health system does not provide genetic testing for this female population, but the discovery opens up a new possibility: “We have already defined new clinical criteria for testing the CDH1 gene – concludes Corso – and they will also be published shortly in the new guidelines of the Italian Association of Medical Oncology”.