Comparison of the efficacy of different combinations of drugs for the treatment of patients with triple-negative breast cancer
Creators: name: Melendez Solano, Elizabeth
Publisher: name: Zenodo
Year: 2022

description: <strong>Background:</strong> Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is characterized by being aggressive, causing recurrence, and metastasis. The name is because it does not have three of the receptors commonly found in breast cancer, such as estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) [1]. Chemotherapy is the treatment currently used for this subtype of cancer, however, it is necessary to create new therapies that help eradicate the disease, since the average survival according to Emens et al. is only 8 to 13 months [2]. Despite this, current clinical trials suggest that immunotherapy plays a fundamental role in understanding better treatment for this devastating pathology [3]. Some recently published studies have evaluated antibodies targeting PD-1 or PD-L1, and these showed that these agents elicited long-lasting and objective responses in patients with other types of cancer, so they are now being evaluated for the treatment of triple-negative breast cancer [4]. In 2019, S. Loibl et al. found that statistically patients treated with Durvalamab in combination with Nab-paclitaxel, followed by a dose of chemotherapy, had a higher response rate (53.4%) than those patients treated with chemotherapy alone (44.2%), however, the difference was not significant [5]. In 2020, a phase III study (KEYNOTE-522) revealed that the combination of Pembrolizumab with platinum neoadjuvant chemotherapy increased the response of patients with triple-negative breast cancer [6], the results of KEYNOTE-522 achieved FDA approval as the first immunotherapy agent for TNBC in its early stages, however, the scientific community argues that it is necessary to continue with clinical trials due to the adverse effects that this treatment causes [7]. In the same year, Jieqiong Liu et al. demonstrated that Camrelizumab in combination with Apatinib had a favorable overall survival rate (43.3%) in patients with TNBC [8]. Later in the beginning of 2021, A. Brufsky et al. first tested the potential activity of Cobimetinib plus atezolizumab and paclitaxel/nab-paclitaxel, achieving unfavorable results as there was no statistically significant increase in patients' overall survival rate [9]. As can be seen, in recent years various treatments have been developed for triple-negative breast cancer, so it is necessary to create research that tells us which is the treatment that has a higher overall survival rate in patients with this subtype of cancer and thus, give an adequate treatment that improves the hope and quality of life of patients. <strong>Research Question:</strong> Which treatment has the highest overall survival rate in patients with triple-negative breast cancer? <strong>Inclusion criteria:</strong> Records of female patients over the age of 18 with triple-negative breast cancer. Records indicating the dose used and adverse events. Records indicating overall survival rate, objective response rate, and partial or complete response to treatment. <strong>Exclusion criteria:</strong> Records with a publication date less than 2017. Records that address another type of cancer. Non-clinical research, such as reviews, meta-analyses and systematic reviews. Records not written in English. <strong>Objectives: </strong> <strong>General objective:</strong> To compare the overall survival rate of different treatments for triple-negative breast cancer. <strong>Specific objectives:</strong> Examine the databases offered at the UACJ and CONRICyT that include scientific and clinical information on cancer. Analyze the articles according to the inclusion and exclusion criteria. Verify the information in each article where drugs for the treatment of triple-negative breast cancer are compared. To conclude which treatment has the highest overall survival rate for patients with triple-negative breast cancer. <strong>Justification:</strong> Triple-negative breast cancer presents an unfavorable prognosis for patients, so new therapies that act against this subtype of cancer are urgently needed. The following years of research will be key to the treatment of this cancer, and ultimately overcome the challenges and adverse effects that it may bring. Therefore, this systematic review aims to conduct research on the combinations of different drugs for the treatment of triple-negative breast cancer, where it will be concluded which treatment has the highest overall survival rate for patients with this type of cancer. In this way, the systematic review obtained will provide us with information on the most effective treatment for patients. <strong>Proposed methodology:</strong> Choosing three databases for search: ScienceDirect, PubMed and EBSCO Host; as well as considering information obtained from Clinical Trials. Selection of search terms with Booleans to find the literature on the subject: ("Triple negative breast cancer") AND (Immunotherapy) AND (OR treatment regimen) Selection of all the articles obtained from the databases through the search. Elaboration of a PRISMA flowchart for the selection of articles to be included in the systematic review. Extraction and synthesis of the important data of each article: drugs and doses used, side effects, overall survival rate, response to treatment, etc. Analysis and conclusion of the data collected according to the inclusion and exclusion criteria. Preparation of a systematic review that contains detailed research and also compares which is the treatment with the highest overall survival rate in patients with triple-negative breast cancer. <strong>References:</strong> [1] T. E. Keenan and S.M. Tolaney, "Role of immunotherapy in triple-negative breast cancer," <em>JNCCN Journal of the National Comprehensive Cancer Network</em>, vol. 18, no. 4. National Comprehensive Cancer Network, pp. 479–489, Apr. 2020, doi: 10.6004/jnccn.2020.7554. [2] L. A. Emens <em>et al.</em> , "Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer A Phase 1 Study Supplemental content," <em>JAMA Oncol</em>, vol. 5, no. 1, pp. 74–82, 2019, doi: 10.1001/jamaoncol.2018.4224. [3] A. R. T. Bergin and S. Loi, "Triple-negative breast cancer: Recent treatment advances [version 1; peer review: 2 approved]," <em>F1000Research</em>, vol. 8. Faculty of 1000 Ltd, 2019, doi: 10.12688/f1000research.18888.1. [4] E. A. Mittendorf <em>et al.</em> , "PD-L1 expression in triple-negative breast cancer," <em>Cancer Immunol. Beef.</em> , vol. 2, no. 4, pp. 361–370, 2014, doi: 10.1158/2326-6066.CIR-13-0127. [5] S. Loibl <em>et al.</em> , "A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study.," <em>Ann. Oncol. Off. J. Eur. Soc. Med. Oncol.</em> , vol. 30, no. 8, pp. 1279–1288, 2019, doi: 10.1093/annonc/mdz158. [6] P. Schmid <em>et al.</em> , "Pembrolizumab for Early Triple-Negative Breast Cancer," <em>N. Engl. J. Med.</em> , vol. 382, no. 9, pp. 810–821, Feb. 2020, doi: 10.1056/nejmoa1910549. [7] P. Tarantino <em>et al.</em> , "Immunotherapy for early triple negative breast cancer: research agenda for the next decade," <em>npj Breast Cancer</em>, vol. 8, no. 1, pp. 1–7, Feb. 2022, doi: 10.1038/s41523-022-00386-1. [8] J. Liu <em>et al.</em> , "Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: An open-label phase II trial," <em>J. Immunother. Cancer</em>, vol. 8, no. 1, May 2020, doi: 10.1136/jitc-2020-000696. [9] A. Brufsky <em>et al.</em> , "A phase II randomized trial of cobimetinib plus chemotherapy, with or without atezolizumab, as first-line treatment for patients with locally advanced or metastatic triple-negative breast cancer (COLET): primary analysis," <em>Ann. </em> <em>Oncol.</em> , vol. 32, no. 5, pp. 652–660, May 2021, doi: 10.1016/j.annonc.2021.01.065.