Several drugs under study and a new trial indicates that recovery can be aimed at with a mix of chemo and immunotherapy before the operation
The so-called triple negative is one of the main subtypes in which breast cancer is classified and among the most difficult to cure, but fortunately scientific research is making important progress and new therapeutic combinations are able to prolong the survival of patients, with good quality of life, as shown by the data of a study just published in the journal New England Journal of Medicine
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More often in young women
With 55 thousand new cases diagnosed in 2020 and 37 thousand Italians living with a metastatic neoplasm, breast cancer is the most common not only among females, but in the entire population. Despite the many advances made (fortunately 87% of patients alive 5 years after diagnosis) remains the leading cause of death from cancer among Italians. Triple-negative carcinoma, which accounts for 15% of breast cancers and is most frequently diagnosed in young women (before 40 years of age), among the most difficult forms to fight because it is biologically more aggressive than other tumor subtypes. In fact, the triple-negative term indicates theabsence of all three markers that somehow guide treatment in the other forms of cancer which instead have well-defined receptors. In this case, however, the neoplastic cells do not have either the receptor for estrogen or for progesterone, that is, those receptors that lead to the definition of a hormone-dependent tumor and make it possible to focus on anti-hormonal therapy.
The various subtypes of breast cancer
Breast cancer is currently classified into three main subtypes, defined according to the receptors present on cancer cells – he explains Michelino De Laurentiis, director of the Department of Breast and Thoraco-pulmonary Oncology at the National Cancer Institute IRCCS Pascale Foundation of Naples -. Specifically, there are so-called tumors “luminaries” which have receptors for estrogen and progesterone and which, for this reason, benefit from hormonal therapies; tumors HER2-positive which have receptors for a growth factor (the HER2 protein) that fuels tumor proliferation, which can be treated with monoclonal antibodies and small molecules; and, finally, i triple negative which have neither the receptor for estrogen, nor that for progesterone or even for the HER2 protein. Even within these categories, however, there are further subgroups and the triple negative is a very heterogeneous subtype, on average biologically aggressive, but not necessarily: there are very aggressive ones and others that are more good. It is precisely by virtue of these numerous differences that biopsy is fundamentala necessary step to understand which specific breast cancer is present in the individual patient, before starting any therapy.
Surgery is not always the first step
Therefore, surgery is not always the correct first step. In the case of triple negative tumors, for example, if these are greater than one centimeter, the best way to follow is the neoadjuvant one, that is treat the tumor with drugs before surgery to reduce it, but above all to receive useful information for the subsequent therapeutic approach and to understand if the tumor is sensitive to the therapies practiced – explains the expert -. In the event that the tumor does not disappear but traces of it are still found during the surgery, it is evident that there are resistant cancer cells to that treatment and this allows us to change medicines in the subsequent post-surgical phase and increase the chances of recovery. Another reason why it is essential to proceed with the characterization of the tumor before operating is that they are on the way new immunotherapy drugs that we can only use in the pre-surgical phase. The results of the newly published KEYNOTE-522 phase three trial also go in this sense, indicating the usefulness of adding pembrolizumab to chemotherapy in women with triple negative breast cancer in the early stages before proceeding with the removal of the tumor and then again with pembrolizumab, which significantly prolongs event-free survival in patients with triple-negative breast cancer (the reduction in risk of adverse events or death by 37% at 39 months). These results change the scenario for patients – comments De Laurentiis – a clear improvement in the prognosis of these tumors and a potential increase in the possibility of recovery.
New therapies on the way
Until recently, only classic chemotherapy was available for triple negatives. For a couple of years for advanced metastatic forms Immunotherapy with atezolizumab and shortly with pembrolizumab is also added, obviously not in all triple negatives, but only in the presence of markers of sensitivity to this treatment – explains De Laurentiis -. Again for the advanced forms, in 2021 new data were presented on one new category of drugs which promises to be particularly effective in breast cancer: drug-conjugated antibodies. In particular (available in Italy with an early access program guaranteed free of charge by the manufacturer) sacituzumab-govitecan a monoclonal antibody loaded with molecules of a very powerful chemotherapy which, thanks to the bond with the antibody, is not released into the blood but reaches the cancer cell and is released only inside it. Then there is another drug in this new category (datumpotomab-deruxtecan), but still in a very early phase of experimentation, even if the results are extremely promising and appears to be particularly effective in triple negative breast cancers.
February 22, 2022 (change February 23, 2022 | 20:23)
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