HER2-positive breast cancer -a vailable anti-HER2 therapies and new agents under investigation

Introduction and objectives. Breast cancer (BC) is the most common malignancy and the leading cause of cancer death among women. About 15–20% of all BCs are HER2-positive. Proper assessment of HER2 status is crucial to choose appropriate treatment. The review summarizes data on anti-HER2 drugs used to treat HER2-positive BC and provides basic information on new agents under investigation. Brief description of the state of knowledge. Specific HER2-targeting drugs are available or are being evaluated in clinical trials. Anti-HER2 agents include: monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates, bispecific antibodies, PI3K/AKT/mTOR inhibitors and heat shock protein 90 inhibitors, HER2-targeting vaccines and CDK4/6 inhibitors. The advent of anti-HER2 therapies increased the time of progression free survival and overall survival in BC patients. Results. Final analysis of the CLEOPATRA trial shows that the combination of trastuzumab, pertuzumab and taxane significantly improved outcomes in metastatic HER2-positive BC and it is currently preferred first-line treatment. The recommended second-line treatment is based on trastuzumab emtansine or on the combination of lapatinib and capecitabine. Some promising agents such as margetuximab or trastuzumab deruxtecan are still under investigation. Conclusions. Anti-HER2 directed treatment undoubtedly improves outcomes among patients with HER2-positive BC. Access to drugs such as trastuzumab, pertuzumab, lapatinib and T-DM1 improves prognosis even in patients with advanced disease. Further studies and clinical trials on novel anti-HER2 therapies are required. Nevertheless, BC treatment is becoming more effective and, hopefully, one day it may be possible to cure patients even with metastases

High-risk HPV test in cervical cancer prevention - present and future

Introduction. Cervical cancer is the fourth most common cancer among women. It is related to persistent HPV infection. In order to improve diagnostic methods, a lot of research has been focused on detecting HPV DNA. A test known as a high- risk HPV test or HPV primary screening provides very encouraging results. Objective.The aim of this review is to present the actual knowledge about the possibilities of cervical cancer screening methods. Particular attention is paid to the question concerning the effectiveness of detecting viral DNA as a screening programme, compared to pap smear. State of knowledge. The HPV primary screening has higher sensitivity than the cervical smear test and it is able to detect lower-stage lesions, which are considered clinically irrelevant. Nonetheless, many HPV infections recede naturally. Therefore, relying only on the results of this test may expose women to unnecessary colposcopies and stress. Due to this fact, women under 30 years should not be screened with the hrHPV test. In view of its limitations, the HPV primary screening strategy is still tested worldwide as a pilot project. In Poland in 2019, a pilot project with the hrHPV test started at the National Institute of Oncology. Conclusions. Detecting viral DNA has its advantages and disadvantages. Further research is still required, but the hrHPV test has a great opportunity to become one of the main screening programmes worldwide, or at least, a valuable addition to cervical smear test

Vegetation impact on stream chemical fluxes : Mule Hole watershed (South India)

The proportion of chemical elements passing through vegetation prior to being exported in a stream was quantified for a forested tropical watershed (Mule Hole, South India) using an extensive hydrological and geochemical monitoring at several scales. First, a solute annual mass balance was established at the scale of the soil-plant profile for assessing the contribution of canopy interaction and litter decay to the solute fluxes of soil inputs (overland flow) and soil outputs (pore water flow as seepages). Second, based on the respective contributions of overland flow and seepages to the stream flow as estimated by a hydrological lumped model, we assigned the proportion of chemical elements in the stream that transited through the vegetation at both flood event (End Member Mixing Analysis) and seasonal scales. At the scale of the 1D soil-plant profile, leaching from the canopy constituted the main source of K above the ground surface. Litter decay was the main source of Si, whereas alkalinity, Ca and Mg originated in the same proportions from both sources. The contribution of vegetation was negligible for Na. Within the soil, all elements but Na were removed from the pore water in proportions varying from 20% for Cl to 95% for K: The soil output fluxes corresponded to a residual fraction of the infiltration fluxes. The behavior of K, Cl, Ca and Mg in the soil-plant profile can be explained by internal cycling, as their soil output fluxes were similar to the atmospheric inputs. Na was released from soils as a result of Na-plagioclase weathering and accompanied by additional release of Si. Concentration of soil pore water by evapotranspiration might limit the chemical weathering in the soil. Overall, the solute K, Ca, Mg, alkalinity and Si fluxes associated with the vegetation turnover within the small experimental watershed represented 10-15 times the solute fluxes exported by the stream, of which 83-97% transited through the vegetation. One important finding is that alkalinity and Si fluxes at the outlet were not linked to the "current weathering" of silicates in this watershed. These results highlight the dual effect of the vegetation cover on the solute fluxes exported from the watershed: On one hand the runoff was limited by evapotranspiration and represented only 10% of the annual rainfall, while on the other hand, 80-90% of the overall solute flux exported by the stream transited through the vegetation. The approach combining geochemical monitoring and accurate knowledge of the watershed hydrological budget provided detailed understanding of several effects of vegetation on stream fluxes: (1) evapotranspiration (limiting), (2) vertical transfer through vegetation from vadose zone to ground surface (enhancing) and (3) redistribution by throughfalls and litter decay. It provides a good basis for calibrating geochemical models and more precisely assessing the role of vegetation on soil processes