Breast cancer, the treatment for those with the “Jolie mutation” changes

Breast cancer, the treatment for those with the “Jolie mutation” changes


There are those who define it as a “family curse”, when the tumor marks the family tree, often following the female line. But that “curse” has a well-known biological explanation called BRCA. Or, rather, hereditary mutations of the two Brca 1 and 2 genes, which predispose to tumors: especially breast and ovarian tumors, but also prostate and pancreatic tumors. Knowing that you are a carrier makes the difference both for prevention and for therapy and prognosis. And today even more: the Italian drug agency has in fact approved the reimbursement of a targeted drug, olaparib, which can now be used from the initial stages of the disease, after surgery, in women with high-intensity hereditary BRCA mutations. risk of recurrence. The drug was in fact already approved, but only for women (always with hereditary BRCA mutations) with triple-negative metastatic cancer.

For whom the treatment changes, and how

According to the new indications, olaparib can be prescribed in all patients with hereditary BRCA mutation, both triple negative breast cancer and aggressive hormone receptor positive (HR+/HER2-), i.e. in which the probability that the disease may return (established by oncologists based on very precise parameters) is high. It will be used as monotherapy or in association with endocrine therapy after surgery in patients already treated with neoadjuvant (i.e. before surgery) or adjuvant chemotherapy. “In the presence of a BRCA mutation, breast cancer tends to occur in a younger population than the average age of diagnosis – he explains Michelino De Laurentiis, Director of the Department of Senological and Thoraco-Pulmonary Oncology, National Cancer Institute IRCCS Fondazione ‘G. Pascale’ of Naples – Most of these tumors, when identified in an early stage, heal. Not all however, and some present a higher risk. Hence the need for new effective treatment tools.”

The study on olaparib

Aifa’s approval follows that of the European Commission in August 2022, based on the results of the Phase III OlympiA study, published in New England Journal of Medicine. Olaparib is the first drug in the class of PARP inhibitors (a group of proteins involved in DNA repair) and in the study it demonstrated a statistically significant and clinically relevant improvement in survival free from invasive disease, reducing the risk of recurrence of the disease. 42%. Furthermore, targeted therapy showed an improvement in overall survival, reducing the risk of death by 32%. “Results – comments De Laurentiis – that we rarely observe and which have changed clinical practice for these tumors”.

Genetic testing right from diagnosis

In Italy it is estimated that approximately 5% of breast cancer patients carry a hereditary BRCA mutation. “It seems like a small percentage, but it translates into around 3,000 cases a year,” specifies De Laurentiis. The fact of being able to use this targeted therapy in the early stages of treatment makes it even more important to carry out the genetic test right from the diagnosis, if there is a suspicion of the presence of a mutation. “The test for BRCA mutations must be performed at the time of diagnosis and is essential both to allow patients to access an effective personalized therapy capable of guaranteeing a good quality of life, and to inform family members about a possible genetic predisposition to the development of the disease – he underlines Laura CortesiHead of the Simple Structure of Oncological Genetics at the Department of Oncology of the University Hospital of Modena – The test can be prescribed by the oncologist, the surgeon or the geneticist, who also become responsible for adequately informing the patient”.

How oncogenetic counseling works

Knowing the mutational status of the Brca genes is also very important for defining the risk of developing other neoplasms and planning personalized clinical management, he underlines Emanuela Lucci Cordisco, medical geneticist at the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome and researcher at the Catholic University of the Sacred Heart. It also allows the identification of healthy family members with the Brca mutation, in which programs can be set up to reduce the risk of developing the neoplasm: “The oncogenetic counseling process for family members, which allows the identification of healthy carriers at high risk and those who have not inherited the mutation and therefore have a lower risk, consists of several phases and ends with the communication of the test result. The BRCA test for the search for constitutional, i.e. heritable, variants is performed in many laboratories in our country, with widely validated methodologies. If the test is positive, effective risk reduction strategies can be implemented, ranging from intensive surveillance to prophylactic surgery.”

Mutations and surgery

The surgical intervention, of course, is also influenced by the outcome of the genetic test, as he explains Corrado Tinterri, Head of the Breast Unit and Director of the Breast UNIT at Humanitas University, IRCCS Humanitas Research Hospital of Rozzano (Milan): “A good quality of life does not only depend on the survival or preservation of the breast, but also on the possibility of not having to reliving the experience of the illness. The risk of a recurrence, both in the operated breast and in the other, must be explained to women with the BRCA mutation. The surgeon must evaluate the option of bilateral mastectomy in a personalized way together with the patient, so as to offer a shared treatment”. It is essential to contact a specialized center with a path for high genetic risk, where multidisciplinary management and collegial evaluation are guaranteed. Even for healthy women with a Brca gene mutation, it is essential to turn to specialized centers that provide active surveillance or ad hoc prevention courses: “The preventive bilateral mastectomy operation – concludes Tinterri – i.e. the surgical removal of both breasts, is able to reduce the risk of developing breast cancer in the future by over 90% in healthy women.”



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