A imunoterapia no tratamento do câncer de mama triplo-negativo: evidências baseadas na revisão sistemática de ensaios clínicos

Abstract

Introduction: Cancer is a worldwide public health problem, being among the four main causes of death. Among women, breast cancer is the most prevalent, with triple-negative representing about 15 to 20% of all types of malignant breast cancer. Triple-negative breast cancer (TNBC) does not have hormone receptors and for the HER2 protein. Therefore, the TNBC has a poor prognosis. The standard treatment, in this case, is chemotherapy, however, even in association with surgery and / or radiotherapy, 60% of patients, with TNBC, have minimal or no response. In this context, immunotherapy emerges as a promising treatment strategy. Objective: To evaluate the effectiveness of immunotherapy in the treatment of triple-negative breast cancer. Method: This is a systematic review of the literature, with scientific articles selected from the databases: PubMed, CAPES Journals, SciELO and BVS. The descriptors were used: “triple-negative breast cancer” and “immunotherapy”, in Portuguese and English. The research was restricted to studies involving human beings, in English, Portuguese or Spanish, published in the last 5 years. Clinical trials were included, with cases of TNBC, with confirmed histopathology, with data on the prognosis of the cancer in question, in response to immunotherapy and markers of response to treatment. 41 articles were identified on the proposed theme. All articles were subjected to critical reading and data analysis. Thus, 10 articles were considered eligible and constituted the sample universe of this systematic review. Results: The studies, grouped together, evaluated 1,400 patients with triple-negative breast cancer undergoing immunotherapy. The following drugs were analyzed: atezolizumab, with and without association with nab-paclitaxel; pembrolizumab; cabozantinib; cyclophosphamide; mesna; thiotepa; and carboplatin. In all studies, there was histopathological confirmation of TNBC and most patients were in an advanced stage of the disease, with the presence of metastases. Most of the participants had received previous treatment, neoadjuvant or adjuvant, with chemotherapy, such as taxanes and anthracyclines. In eight of the ten studies, the expression of programmed cell death ligand-1 (PD-L1) was quantified, and in two of the clinical trials, this expression was an inclusion criterion. PD-L1 expression was associated with a better response to treatment. Patients were followed up, on average, for 10.6 months. Adverse effects were present in all studies and presented themselves in a variable way, however, adverse effects considered serious were rare. The best objective response rate was obtained by the treatment performed by combining atezolizumab with nab-paclitaxel. As for disease control, the study that showed the best rate (70%) used treatment with granulocyte colony stimulating factor associated with initial chemotherapy. The mean time of disease-free progression was 4.4 months, ranging from 1.7 to 13.5 months. The median overall survival, found in the studies, was 13.6 months, and the median was 15.9 months, with a range from 7.6 to 20.7 months. Several tumor markers were evaluated, however, the most important in the studies and, apparently, with greater responsiveness to immunotherapy, was the PD-L1. Conclusion: It is concluded that immunotherapy is a very promising modality in the treatment of triple-negative breast cancer, in monotherapy or in association with other strategies. The existence of tumor-infiltrating lymphocytes and the expression of PD-L1 were predictors of a positive response to certain immunotherapeutic treatments. However, further studies are needed to verify new therapeutic targets for the development of new drugs.