Clinical relevance of the deregulated kallikrein-related peptidase 8 mRNA expression in breast cancer: a novel independent indicator of disease-free survival

Examining for new BC biomarkers has proven that kallikrein-related peptidase (KLK) family members represent promising serum and/or tissue molecular tools for early diagnosis, effective prognosis, and treatment monitoring of patients. The aim of this study was to investigate, the previously unexplored, prognostic significance of KLK8 in BC. KLK8 mRNA expression was quantitatively analyzed in 150 cancerous and 100 corresponding normal breast tissue specimens via a SYBR Green-based Real-Time PCR methodology. Expression data and patients’ clinicopathological parameters were used for extensive biostatistical analyses, including internal validation. KLK8 mRNA expression was significantly downregulated in the cancerous tissue part relative to the non-cancerous counterpart (P\0.001), in the majority of the paired breast tissue samples. KLK8 expression was associated with advanced TNM stage (P = 0.019) and positive nodal status involvement (P = 0.044). Triple negative (TNBC) and HER2 overexpressing tumors exhibited higher KLK8 expression levels (P\0.001), compared to Luminal A and B molecular subtypes. Kaplan–Meier survival curve analysis revealed that BC patients with high KLK8 expression had significantly shorter disease-free survival (DFS) intervals (P\0.001) compared to those belonging in the KLK8-low expression group. Cox univariate analysis confirmed the association between KLK8 expression, analyzed as a continuous variable, and poor patients’ outcome (Hazard ratio [HR] = 3.28, P\0.001). Most importantly, multivariate analysis showed that KLK8 expression is a strong and independent predictor of adverse DFS in BC ([HR] = 2.74; P = 0.002). Our results show that KLK8 mRNA expression is associated with aggressive tumor characteristics and it can serve as a novel independent biomarker of unfavorable prognosis for BC patients

Bilateral De Quervain Syndrome after Aromatase Inhibitor Administration: A Case Report and Review of the Literature

Aromatase inhibitors are widely used as one of the main treatment options of both early and advanced hormone receptor-positive breast cancer in postmenopausal women. Unfortunately, musculoskeletal symptoms are often presented in patients treated with aromatase inhibitors (AIs), and, although the pathogenesis is unknown, postulated mechanisms have been described. Herein, to our knowledge, we present the first report of bilateral De Quervain syndrome related with AIs therapy with a review of the relevant literature

The Role of BCL2 Family of Apoptosis Regulator Proteins in Acute and Chronic Leukemias

The disturbance of apoptosis molecular signaling pathways is involved in carcinogenesis. BCL2 family of proteins is the hallmark of apoptosis regulation. In the last decade, new members of BCL2 gene family were discovered and cloned and were found to be differentially expressed in many types of cancer. BCL2 protein family, through its role in regulation of apoptotic pathways, is possibly related to cancer pathophysiology and resistance to conventional chemotherapy. It is well known that leukemias are haematopoietic malignancies characterized by biological diversity, varied cytogenetics, different immunophenotype profiles, and diverse outcome. Current research focuses on the prognostic impact and specific role of these proteins in the pathogenesis of leukemias. The understanding of the molecular pathways that participate in the biology of leukemias may lead to the design of new therapies which may improve patients' survival. In the present paper, we describe current knowledge on the role of BCL2 apoptosis regulator proteins in acute and chronic leukemias

Epidemiological characteristics, clinical outcomes and management patterns of metastatic breast cancer patients in routine clinical care settings of Greece: Results from the EMERGE multicenter retrospective chart review study

Abstract Background The “EMERGE” study, aimed to capture real-life management patterns and outcomes in metastatic breast cancer (MBC) in Greece, also accounting for hormone (HR) and human epidermal growth factor receptor 2 (HER2) status. Methods “EMERGE” was a multicenter, retrospective cohort study of adult MBC patients diagnosed between 01-Janaury-2010 and 30-June-2012, either de novo or having progressed from a non-metastatic state. Patient data, including treatment patterns and outcomes, were mainly abstracted through medical chart review. Results 386 patients were enrolled by 16 hospital-based oncologists between 12-March-2013 and 31-March-2015. The median look-back period was 29.1 months. At MBC diagnosis, 56.1% of the patients were HR+/HER2−, 16.6% HR+/HER2+, 14.5% HR−/HER2−, and 12.8% HR−/HER2+. In the first line setting, chemotherapy, targeted therapy and endocrine therapy were received by 76.7, 52.4, and 28.3% of the overall population, and by 66.5/36.2/42.0%, 80.4/80.4/28.6%, 88.4/90.7/0.0, and 95.6%/56.5/6.5% of the HR+/HER2−, HR+/HER2+, HR−/HER2+, HR−/HER2− subpopulations, respectively. In the overall population, the disease progression incidence rate was 0.57 [95% confidence interval (CI): 0.48–0.67] per person-year; median progression-free survival (PFS) was 22.4 (95% CI: 20.4–24.7) and overall survival (OS) was 45.0 (95% CI: 40.9–55.0) months. Median PFS was 24.6 (95% CI: 21.3–27.9) in HR+/HER2−, 19.7 (95% CI: 12.9–25.9) in HR+/HER2+, 23.0 (95% CI: 16.6–29.7) in HR−/HER2+ and 18.3 (95% CI: 10.0–24.7) months in HR−/HER2− subpopulations. A multivariable Cox proportional hazards model, adjusted among other factors for age and duration of diagnosis, HR and HER2 status, demonstrated that in the overall population PFS was better among those receiving first line endocrine therapy (hazard ratio: 0.70; 95%CI: 0.51–0.95; p = 0.024). Conclusions “EMERGE” demonstrates differences between HR/HER2 subtypes in clinical outcomes and divergence from evidence-based guideline recommendations for MBC management, especially as it pertains to the HR+/HER2− patients in which chemotherapy was favored over endocrine therapy in the first line setting. Study registration The study has been registered on the electronic Registry of Non-Interventional Studies (RNIS) posted on the website of the Hellenic Association of Pharmaceutical Companies (SFEE): https://www.dilon.sfee.gr/studiesp_d.php?meleti_id=NIS-OGR-XXX-2012/

Are Thyroid Hormone and Tumor Cell Proliferation in Human Breast Cancers Positive for HER2 Associated?

Objective. This study investigated whether thyroid hormone (TH) levels are correlated to cell proliferation (Ki67), in euthyroid breast cancer patients. Design and Methods. 86 newly diagnosed breast cancer patients with estrogen receptor (ER) positive tumors, who referred for surgery, were included in the study. Results. FT3, FT4, and TSH were within normal range. No correlation was seen between Ki67 and FT3 (r=-0.17, P=0.15), FT4 (r=-0.13, P=0.25), or TSH (r=-0.10, P=0.39) in all patients studied. However, subgroup analysis showed that, in HER2(+) patients, a negative correlation existed between FT3 levels and Ki67 (r=-0.60 and P=0.004) but not between Ki67 and FT4 (r=0.04 and P=0.85) or TSH (r=-0.23 and P=0.30). In HER2(−) patients, there was no significant correlation between Ki67 and FT3 (r=-0.06, P=0.67), FT4 (r=-0.15, P=0.26), or TSH (r=-0.09, P=0.49). Phospho-p44/total p44 ERK levels were found to be increased by 2-fold in HER2(+) versus HER2(−) tumors. No difference was detected in phospho-p42/total p42 ERK levels. Conclusions. TH profile is not altered in patients with newly diagnosed breast cancer. However, FT3 levels, even within normal range, are negatively correlated with cell proliferation in HER2(+) breast cancer tumors. This response may be due to the interaction between ERK and TH signaling