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 evidenced by the data of one 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 live 5 years after diagnosis) it remains the leading cause of death from cancer among Italians. Triple-negative breast cancer, which accounts for 15% of breast cancers and is most frequently diagnosed in young women (before the age of 40), is one of the most difficult forms to combat because it is biologically more aggressive than other tumor subtypes. In fact, the triple-negative term indicates the absence of all three markers that in some way guide the treatment in other forms of cancer that 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 – 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 “luminal” tumors which have receptors for estrogen and progesterone and which, for this reason, benefit from hormonal therapies; there are the so-called HER2-positive tumors, which have receptors for a growth factor (the HER2 protein) that feeds tumor proliferation, which can be treated with monoclonal antibodies and small molecules; and, finally, there are triple negative tumors that do not have any of the three main receptors (neither the estrogen receptor, nor the progesterone receptor, nor 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 and other more good ones. It is precisely because of these numerous differences that biopsy is fundamental, a 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 a centimeter, the best way to follow is the neoadjuvant one, that is to treat the tumor with drugs before surgery to reduce it, but above all to receive useful information for the subsequent therapeutic setting. 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 surgery, it is evident that there are tumor cells resistant 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 new immunotherapy drugs are on the way that we can only use in the pre-surgical phase. the results of the KEYNOTE-522 phase three trial just published indicating that it is useful to add pembrolizumab to chemotherapy in women with early stage triple negative breast cancer prior to tumor removal and then again with pembrolizumab to significantly prolong 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 soon with pembrolizumab has also been 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 a new category of drugs that 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 22, 2022 | 09:36)
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