It is a rare mutation, but women who have it have an 80-90% chance of developing breast cancer in their lifetime. Even from a very young age, before the age of 30. We are talking about the mutation of the TP53 gene (or P53, the name of the protein), well known to oncologists because it has a crucial task: to stop cells when their DNA is damaged, to prevent them from replicating and giving rise to tumours. And mutations can compromise this very important function.
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It interferes with Tp53
Although TP53 is so “famous” and studied, its role in breast cancer is still not fully understood. For patients who are carriers of mutations, there are currently not enough data to be able to give precise indications, especially in terms of therapies, the risk of recurrence and prognosis. This was underlined by an international group of researchers coordinated by the University of Genoa in a review recently published on Cancer Treatment Reviews. “We know that about 5% of all breast cancers have a genetic predisposition at the base – explains a Breast health Eva Blondeauxresearcher at the Irccs Policlinico San Martino and first author of the publication – Half of the cases depend on mutations in the BRCA genes, but there are other genes responsible, and among these TP53, which increases the risk of getting sick more than BRCA mutations “.
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Breast cancer, the 8 genes of heredity
by Tiziana Moriconi
Young age and familiarity: who is the onco-genetic visit for?
We said that TP53 is a rare mutation, but how rare? If we consider an unselected population of patients with breast cancer, the percentage of cases is even below 0.5%. But the story changes if you look at young women, with the Her2 positive histological type or with a strong family history of tumors of the breast, gastrointestinal, pancreas, brain, soft tissue such as sarcomas, prostate, or leukemia: in these cases the percentage can even reach 5-10%. Familiarity, young age and Her2 positive tumor are in fact the criteria that lead oncologists to suspect that they are dealing with a patient carrying a TP53 mutation. Which – as Blondeaux says – should always be sent to a medical genetics center for evaluation, under which genetic testing can then be offered.
Bianca Balti and preventive mastectomy, why it is done and what the BRCA mutation is
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Guidelines for those with the TP53 mutation
As in the case of BRCA, here too we are talking about hereditary mutations. Precisely for this reason, if there is a suspicion of a mutation, it is important to contact centers able to offer not only a simple genetic test, but also onco-genetic counseling and a process of taking care of both the patient and her family. “Panels for the simultaneous search for mutations in many genes – underlines Blondeaux – are increasingly used in clinical practice, but pose serious ethical and medical questions: it is counterproductive to identify mutations in rare genes whose meaning we do not know and for which there is no adequate pathway for taking charge”.
Breast cancer prevention must start young
by Tiziana Moriconi
With regard to breast cancer screening in healthy people – he continues – for those who know they have a TP53 mutation, international guidelines today recommend an annual breast MRI scan starting from the age of 20 and to discuss the possibility of a mastectomy prophylactic (which, however, as happens for mutations of the BRCA genes, is not yet in the Lea and therefore the reimbursement often depends on regional funds or made available by the hospitals themselves). On the treatment front, however, the guidelines suggest mastectomy instead of conservative surgery and avoiding radiotherapy, since radiation could further increase the risk of second tumors in these patients. It is also necessary to evaluate preventive mastectomy of healthy breasts.
Hereditary cancers and genetic risk: only one in 10 cases identified
by Irma D’Aria
A new study is underway
“We still don’t know, however, what their real risk of relapse or of a second cancer in healthy breasts is, or if their prognosis is worse than those who do not have the TP53 mutation – underlines the researcher. That a new project is about to start of research to clarify these aspects, thanks to the Fellowship Program tender promoted by Gilead Sciences Blondeaux is in fact one of the young scientists who won the last edition of the tender reserved for researchers, which in 11 years funded 397 projects with 9.6 million euros 47% of these were won by women (the XII edition of the Gilead Sciences tenders opened last week: the Fellowship Program for researchers with prizes of 30,000 euros, and the Community Award for patient associations with prizes from 5 to 50 thousand euros, plus special prizes of 60 thousand euros). “My research project – explains Blondeaux – involves the enrollment of patients with breast cancer regardless of the TP53 mutation. We will therefore go on to study and compare the risk of recurrence, second cancers and survival, in early and advanced stages, between patients carrying the TP53 mutation and patients without the mutation”. The goal? To have more solid data on which to build prevention protocols, early diagnosis and therapies.