2023-09-11 18:54:20
by Vera Martinella
Metaplastic carcinoma is uncommon, but very aggressive and responds poorly to available therapies. Research discovers that it may be linked to a mutation of the BRCA1 gene and opens up new treatment prospects
Every year in Italy around 55 thousand women fall ill with breast cancer (and more or less 500 men: although it is a very uncommon disease in men, the possible alarm bells should not be overlooked). Scientific research has now clearly indicated that there are many different types of this form of cancer and it is essential to know which histological and molecular subtype you are dealing with in order to be able to choose, among the many therapies available, the most effective one based on the individual case: a step decisive for having a greater chance of recovery. However, not much is known yet about metaplastic breast cancer, a rare and particularly aggressive form, but an Italian study has recently made an important step forward.
Mutation of the BRCA1 gene
The research conducted by the European Institute of Oncology (Ieo) and recently published in the scientific journal European Journal of Human Genetics
, demonstrates for the first time the existence of a link between this fearful subtype of breast cancer and mutations of the well-known BRCA1 gene: the results obtained on a large series of patients subjected to genetic testing of the BRCA1 and BRCA2 genes, therefore selected on based on their personal and family oncological history, show that a high percentage of diagnosed metaplastic tumors are hereditary. A fact that has so far been completely unknown – underlines Giovanni Corso, IEO breast surgeon, university researcher at the University of Milan and first author of the study -. Metaplastic breast cancer is still mostly a mystery: we know that it is rare (less than 5% of all breast cancers), that it frequently affects young women and that unfortunately it responds very poorly to therapies. But we don’t know why. For this reason, the discovery of its possible link with BRCA1 finally opens up new horizons of treatment, with new generation drugs that have demonstrated effectiveness against tumors presenting this mutation. The importance of this innovation (as underlined Gareth Evans, authoritative geneticist at Manchester University Hospital, in an editorial published in the same scientific journal) lies in the possibility of better understanding the mechanisms of birth and development of a particularly complex and heterogeneous subtype of cancer, such as metaplastic cancer, to increase treatment options, which are currently limited and poorly effective.
Therapies and genetic testing
Metaplastic breast cancer can currently be treated (when operable) only with surgery – explains Corso -. However, very often, and especially in advanced cases, it presents with distant metastases, where the possibilities of cure are really reduced to a minimum. Unfortunately, there are no “targeted” therapies: a previous IEO study demonstrated the very limited effectiveness of chemotherapy and an American study from the Memorial Sloan Kettering Cancer Center in New York reached the same conclusion. So what actually changes with the new discovery? It allows us to classify the metaplastic tumor as a new rare hereditary syndrome – replies the researcher -. All women newly diagnosed with this subtype of cancer should be tested for the BRCA1 gene, regardless of age and family history. The presence of a BRCA1 mutation allows, in fact, to evaluate new therapeutic strategies such as the use of PARP inhibitors, not allowed until now, but already used successfully for other types of BRCA-positive cancer.
More invasive surgery
Not only. In light of this news, the surgeon’s choice may also change, as illustrated by Paolo Veronesi, director of the Ieo Senology Program: Aside from the new pharmacological therapeutic options foreseen for metaplastic tumors which certainly open up new treatment horizons, our results clearly demonstrate that conservative surgery (quadrantectomy for example) may no longer be sufficient to cure this rare variant of breast cancer, especially in the presence of the BRCA1 gene. The risk of recurrence could be very high, particularly in young women. Therefore the surgical options should be more “aggressive”, such as therapeutic mastectomy, but also contralateral “risk reducing” prophylactic mastectomy (i.e. preventive removal of even the “healthy” breast to limit the risk of cancer) and integrated plastic reconstruction. Of course, further confirmation is needed on larger series of patients, but as happens with other rare, often poorly curable tumors, even initial results open up a concrete window of opportunity for treatment.
The study of 5,226 patients
Some studies had already reported the possible role of BRCA1 in increasing the risk of metaplastic cancer, but our work is the first to demonstrate, with a retrospective analysis of 5,226 breast cancer patients undergoing genetic testing in Ieo, that beyond 50% of metaplastic tumors are significantly associated with the presence of BRCA – says Bernardo Bonanni, director of the Division of Oncology Prevention and Genetics and co-author of the study, together with Mariarosaria Calvello, co-author and Monica Marabelli, corresponding author of the article (both from the same Division) —. Firstly, we observed a higher frequency of metaplastic tumors in patients carrying mutations in the BRCA genes: 1.2% compared to 0.2% detected in non-mutated patients. Then we found that in this subgroup all patients carried BRCA1 and none of BRCA2. These findings confirm that metaplastic tumor has a clear hereditary predisposition associated with BRCA1. However, these are results obtained on a highly selected series of cases. For this reason, other studies on unselected patient populations with genetic testing are needed to understand the true role of the BRCA1 gene in the onset of metaplastic breast cancer. It will also be important to study the involvement of other genes in the origin of this rare form of tumor.
11 September 2023 (modified 11 September 2023 | 18:43)
© ALL RIGHTS RESERVED
#Breast #cancer #hereditary #origin #rare #form #discovered #time.news