Vilka läkemedelsframsteg har förbättrat prognosen för HER2-positiv metastaserad bröstcancer? : En litteraturstudie

Sammanfattning: Breast cancer is one of the deadliest forms of cancers in the world. About 15–30% of all breast cancers are HER2-positive, which involves overexpression of HER2-receptors on the surface of tumor cells. HER2-positive breast cancer is viewed as an aggressive form of cancer because the overexpression of the HER2-receptor causes dimerization with other receptors of the same family; together they bind to ligands and become activated. The activation causes fast, uncontrolled cell proliferation that often results in the formation of a tumor. Cancer can be divided into different stages, at stage 4 the cancer cells from the original tumor breaks away, follows the bloodstream, and forms metastases in other places of the body. When cancer evolves and becomes metastatic the prognosis drastically worsens, and the treatment options are limited. Patients often need several lines of cancer treatment. The first line of treatment is usually trastuzumab in combination with pertuzumab and a taxane, second line is usually trastuzumab emtansine. There is no conclusive third line treatment for HER2-positive metastatic breast cancer (MBC). Due to the development of new anti-HER2 treatments over the last two decades, less patients are dying from breast cancer, however most patients diagnosed with HER2-positive MBC are estimated to face an early death.  The objective of this study was to analyze the pharmaceutical advances that has improved the prognosis for patients diagnosed with HER2-positive MBC. The material, on which this study was based on, was obtained from the Pubmed database via the Linnaeus University Library. Five articles were chosen based on criteria relevant to the topic. The articles were published between 2001 and 2021; all of them were randomized controlled trials (RCT).  The subject of the articles was to compare the efficacy and safety of different forms of anti-HER2 treatments, using patient populations diagnosed with HER2-positive MBC. Mainly the patients' disease progression, treatment response and survival time was analyzed. Pharmaceutical safety was assessed by the rate of adverse events. A total of 2513 patients participated in the studies. Among all the different treatment options that were analyzed in the articles, one treatment combination yielded some of the best results. Pyrotinib in combination with capecitabine increased the disease progression-free time, had the highest proportion of patients who responded to treatment as well as the highest proportion of patients with size-reducing lesions for the longest time. However, the patient group receiving pyrotinib also had the highest incidence of serious adverse events and had the largest percentage of patients who chose to discontinue the study due to adverse events.  Analysis of the five articles concludes that the prognosis for patients diagnosed with HER2-positive MBC has been improved by pharmaceutical advances regarding tyrosine kinase inhibitors, pan-HER inhibitors, combination therapy with monoclonal antibodies (single, mixed, modified or conjugated with other drugs) and chemotherapy with different mechanisms of action. The results from the studies indicated that treatment with a single anti-HER2 drug had the lowest effectiveness, and that some drug combinations had better synergistic effects than others, reflecting on patient survival data. Despite the pharmaceutical advances of the past two decades, the prognosis for HER2-positive MBC can still be considered bleak due to its high death rate. Resistance to anti-HER2 drugs is an ongoing concern that requires more research and development of new treatments.