BRCA mutation, a new strategy to delay menopause in “healthy carriers” (such as Angelina Jolie and Bianca Balti) – breaking latest news

Mutation of the BRCA1 and BRCA2 genes exposes you to a greater likelihood of developing breast, ovarian, prostate and pancreatic cancer. This is why it is important that in certain families, when there is a well-founded suspicion that these alterations are present, the necessary tests are carried out to find out whether there actually is a genetic risk or not. It is the path they have made, making it known to the general public, both the American actress Angelina Jolie is the Italian model Bianca Balti and which led them to the difficult decision to undergo the mastectomy (the removal of the breast, followed by reconstruction) and to removal of tubes and ovaries to avoid getting cancer. A tiring choice, which many women have to face every year taking into account various factors: from the strong psychological impactof course, until desire to have children and the health problems associated with going through menopause at a young age. For this reason, preventive strategies are being studied that can put young women “sheltered” from the danger of a tumor, but at the same time be less invasive. An example of this is the experimental protocol TUBAII-WISP study, which sees the collaboration of many centers around the world and the participation of Italian experts from San Gerardo in Monza and the Gemelli Polyclinic in Rome and which aims to perform at first the removal of only the fallopian tubes and then that of the ovariesthus delaying the onset of menopause and reducing both discomfort and ‘side effects’.

How high is the risk

«Women who are carriers of an inheritable mutation affecting the gene BRCA1 they have about the 60% chance (versus 10% of the general population) to develop a breast cancer and about 40% (compared to 1-2% of the general population) to develop ovarian cancer in their lifetime – he explains Robert Fruscio, associate professor of Gynecology at the University of Milan Bicocca and in force at the Surgical Gynecology of the IRCCS San Gerardo Foundation -. In the case of mutation of the BRCA2 gene, the percentages are similar for breast cancer and lower for ovarian cancer (about 20%)”.

What changes for those with the mutation

Intercept a “healthy carrier” (i.e. a person who is BRCA positive but not diagnosed with cancer) allows you to offer him two prevention strategies: the first, a “strict” surveillance program with some diagnostic tests to be performed even every six months, different from the screening tests to which the general population is subjected which allows in some cases (for example in breast cancer) to identify the possible onset of a tumor in a very early stage, which can greatly change the prognosis of the disease. The other way is to offer the preventive breast surgery (mastectomy) and that of tubes and ovaries (adnexectomy), or to remove those organs in which a neoplasm could be born with a high probability. “The surgical options require a multidisciplinary approach that is possible in many treatment centers in Italy (such as the Breast Units and specialized centers for ovarian surgery) – he says Alberta Ferrari, Coordinator of the Scientific Technical Committee of theaBRCAdabra association, the first born for carriers of BRCA oncogenetic mutations it sayspatient of the path Hereditary Breast Ovary Tumors at the IRCCS Foundation Policlinico San Matteo University of Pavia —. The woman’s decision must naturally take into account her life choices, her personal and family planning, the desire for motherhood, the results of early menopause and aesthetic and naturally psychological aspects. The data subject must receive all the correct information in order for her to be able to freely choose when and whether to undergo risk reduction surgeryknowing that it is currently the only strategy capable of significantly reducing the risk of developing a tumor in these two organs and in particular in the ovary where, to date, there is not even the option of early diagnosis to bet on”.

Preventive removal of tubes and ovaries

«In women who carry mutations of the BRCA 1-2 genes, a salpingo-oophorectomy surgery (that is, the removal of tubes and ovaries) around the age of 40 – Fruscio clarifies -: they have an increased risk of developing ovarian cancer and surveillance with ultrasound, in terms of anticipating the diagnosis, has given disappointing results. Furthermore, the mortality rate of ovarian cancer is high, also because it does not give symptoms in the initial stage and is identified in the majority of cases in an advanced stage. The effects of prophylactic surgery are a decrease in the risk of ovarian cancer (80-96%) on the one hand and the immediate start of menopause and the consequent disturbances on the other”. Hence the TUBA-WISP II study: numerous scientific researches have indicated that the majority of high-grade serous ovarian carcinomas (the most dangerous ones) develops at the end of the fallopian tube, for which the experts have hypothesized to initially remove only the tubes and postpone that of the ovaries which involves the entry into early menopause. «This makes it possible to provide adequate oncological prevention, because the tubes, from which the carcinoma originates, are removed, but at the same time it allows to postpone the menopause and the known harmful effects on the cardiovascular, bone and nervous systems central. The referral is especially important for women who have had breast cancer and are therefore unable to take hormone replacement therapy. It is a strategy already adopted in some centers and some patients ask to be subjected to this treatment, but for it to become the standard, it is necessary to study the long-term effects on the incidence of ovarian cancer”.

The experimentation

The experimentation (recruitment is already open and interested Italian women can contact the tough Italian contacts: Robert Fruscio at San Gerardo in Monza and Giovanni Ricambia for the Gemelli Polyclinic in Rome) plans to enroll 3,000 women who are healthy carriers of BRCA1-2 mutations worldwide. Each participant, duly informed, will be able to choose between the standard treatment i.e. bilateral adnexectomy for BRCA1-mutated at a maximum age of 40 years (recommended between 35 and 40 years) and BRCA2-mutated at a maximum age of 45 (recommended between 40 and 45 years) or the innovative strategy which provides for bilateral salpingectomy on exhaustion of the desire for offspring within 40 and 45 years for women with BRCA1 and BRCA2 mutation carriers, respectively, with delayed bilateral oophorectomy (within 45 years for BRCA1 and 50 years for BRCA2). «We must remember that for healthy people, testing positive for the mutation means knowing about having a higher risk (not a certainty) of getting certain types of cancer – concludes Fruscio -. And that the BRCA test is carried out free of charge through the NHS when there is a clear utility, established according to precise criteria that are the same throughout the national territory”.