Prognostic Significance of Low HER2 Expression in Patients With Metastatic Hormone Receptor-positive Breast Cancer Treated With First Line CDK4/6 Inhibitors: A Greek Multicenter Real-world Data Analysis.

BACKGROUND/AIM: Low expression of HER2 has defined a new "HER2-low" subgroup of breast cancer with distinct clinicopathological characteristics and both prognostic and predictive implications. The impact of low HER2 expression in metastatic hormone receptor-positive HER2-negative breast cancer treated with first-line CDK4/6 inhibitors has not been studied. Using real-world patient data, we aimed to identify prognostic differences in this patient population according to HER2 expression with immunohistochemistry. PATIENTS AND METHODS: We retrospectively analyzed 191 patients from 5 Oncology Department databases in Thessaloniki, Greece, with hormone receptor-positive HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors in the first line, for whom detailed immunohistochemical HER2 data could be retrieved. RESULTS: Median progression-free survival was numerically different among the different HER2 subgroups (3.35 years for HER2 0 tumors, 2.18 years for HER2 +1 tumors, 1.74 years for HER2 +2/ISH-negative tumors), but this difference was not statistically significant (p=0.477). Median PFS was statistically significantly longer in patients without visceral metastases (5.45 years) compared to patients with visceral metastases (1.61 years) (p=0.017). Median PFS was also statistically significantly longer in patients taking an aromatase inhibitor (2.99 years) compared to patients taking fulvestrant (1.33 years) (p<0.0001). There were no statistically significant differences in the other subgroups examined. CONCLUSION: CDK4/6 inhibitors are equally effective as first-line treatment agents, regardless of the exact level of HER2 expression. Numerical differences, however, do exist among the different HER2 subgroups, and merit further evaluation in future studies to better study this phenomenon.

Clinical feasibility of NGS liquid biopsy analysis in NSCLC patients.

BACKGROUND: Analysis of circulating tumor nucleic acids in plasma of Non-Small Cell Lung Cancer (NSCLC) patients is the most widespread and documented form of "liquid biopsy" and provides real-time information on the molecular profile of the tumor without an invasive tissue biopsy. METHODS: Liquid biopsy analysis was requested by the referral physician in 121 NSCLC patients at diagnosis and was performed using a sensitive Next Generation Sequencing assay. Additionally, a comparative analysis of NSCLC patients at relapse following EGFR Tyrosine Kinase Inhibitor (TKIs) treatment was performed in 50 patients by both the cobas and NGS platforms. RESULTS: At least one mutation was identified in almost 49% of the cases by the NGS approach in NSCLC patients analyzed at diagnosis. In 36 cases with paired tissue available a high concordance of 86.11% was observed for clinically relevant mutations, with a Positive Predictive Value (PPV) of 88.89%. Furthermore, a concordance rate of 82% between cobas and the NGS approach for the EGFR sensitizing mutations (in exons 18, 19, 21) was observed in patients with acquired resistance to EGFR TKIs, while this concordance was 94% for the p.T790M mutation, with NGS being able to detect this mutation in three 3 additional patients. CONCLUSIONS: This study indicates the feasibility of circulating tumor nucleic acids (ctNA) analysis as a tumor biopsy surrogate in clinical practice for NSCLC personalized treatment decision making. The use of new sensitive NGS techniques can reliably detect tumor-derived mutations in liquid biopsy and provide clinically relevant information both before and after targeted treatment in patients with NSCLC. Thus, it could aid physicians in treatment decision making in clinical practice.

Use of proteins as biomarkers and their role in carcinogenesis.

SUMMARY: Improved diagnostic methods and medical therapies are necessary for early detection and treatment and an improved prognosis. It is thus vital to both examine and evaluate the role of the various existing proteins as biomarkers in carcinogenesis and to assess the contribution of these proteins in anti-cancer activity, for consideration in therapeutic strategies. It is essential to both examine and evaluate the role of the various existing proteins as biomarkers in carcinogenesis and to assess the contribution of these proteins in anti-cancer activity, for consideration in therapeutic strategies. The purpose of this review is twofold. Firstly, it is to evaluate recent data about which proteins can be utilized as biomarkers in carcinogenesis. The proteins reviewed include: CPTP, IL-6, CCN, and S100. Secondly, it is to evaluate the contribution of dietary proteins in cancer activity. Specifically, how whey protein, soy proteins and lectin, a phytochemical could be useful in cancer prevention and treatment. RECENT FINDINGS: Whey protein, present in dairy products, is an excellent source of the sulphur amino acid cysteine, the rate limiting substrate in glutathione synthesis. Notably, this protein survives digestion and has been shown to have anti-carcinogenic properties in animal studies. Lectins are phytochemicals present in plant foods, and have active components which alters cancer initiation, promotion and progression. Lectins have been characterized as a useful tool in biochemistry, cell biology, immunology and in diagnostic and therapeutic purposes in cancer research. Soy proteins contain various compounds, including isoflavones, protease inhibitors and protein kinase inhibitors, which have been proven effective in tumor growth inhibition. They have therefore, been greatly emphasized in cancer prevention and treatment. It has been proved that soy food consumption was associated with decreased risk of death and recurrence of breast cancer. CPTP is a recently discovered protein whose main role is to transport C1P, a pro-inflammatory molecule. The discovery of CPTP may shine a light on the mechanism of inflammatory diseases, and hopefully offer a potential target for therapeutic purposes in cancer research. Interleukin-6 is a multifunctional cytokine that affects the activity of cancer cells. It is involved in tumor growth, and elevated levels is associated with an increased risk of cancer. S100B is a well-established biomarker for malignant melanoma, and useful in assessing tumor load, stage and prognosis for patients with this disease. Other members of this family of proteins include S100A4, which has been associated with several malignancies and S100A2, which has been found to be decreased in some cancers. CCN are a group of regulatory proteins, located in the extracellular matrix (maricellular). They are involved in cellular adhesion, mitogenesis, chemotaxis, cell survival, and wound healing. CCN proteins are also able to modulate the signals of several proteins, which may also influence skeletal development and angiogenesis. Many of the functions of these proteins are thus also related to tumor growth. Furthermore, CCN interacts with estrogen in the development of cancer, and is implicated in some breast and ovarian cancers.

Review of mitral valve insufficiency: repair or replacement.

Mitral valve (MV) dysfunction is the second-most common clinically significant form of valvular defect in adults. MV regurgitation occurs with the increasing frequency of degenerative changes of the aging process. Moreover, other causes of clinically significant MV regurgitation include cardiac ischemia, infective endocarditis and rhematic disease more frequently in less developed countries. Recent evidence suggests that the best outcomes after repair of severe degenerative mitral regurgitation (MR) are achieved in asymptomatic or minimally symptomatic patients, who are selected for surgery soon after diagnosis on the basis of echocardiography. This review will focus on the surgical management of mitral insufficiency according to its aetiology today and will give insight to some of the perspectives that lay in the future.

Lung inflammatory response syndrome after cardiac-operations and treatment of lornoxicam.

The majority of patients survive after extracorporeal circulation without any clinically apparent deleterious effects. However, disturbances exist in various degrees sometimes, which indicate the harmful effects of cardiopulmonary bypass (CPB) in the body. Several factors during extracorporeal circulation either mechanical dependent (exposure of blood to non-biological area) or mechanical independent (surgical wounds, ischemia and reperfusion, alteration in body temperature, release of endotoxins) have been shown to trigger the inflammatory reaction of the body. The complement activation, the release of cytokines, the leukocyte activation and accumulation as well as the production of several "mediators" such as oxygen free radicals, metabolites of arachidonic acid, platelet activating factors (PAF), nitric acid, and endothelin. The investigation continues today on the three metabolites of lornoxicam (the hydroxylated metabolite and two other metabolites of unknown chemical composition) to search for potential new pharmacological properties and activities.