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Aim: We evaluated whether the concurrent β-blocker use in early breast cancer patients influenced the outcome in terms of preventing tumor recurrence after adjuvant chemotherapy. Methods: We retrospectively reviewed the medical records of 610 patients with breast cancer. Thereafter, we compared overall disease-free survival (DFS) between β-blocker users and nonusers. Results: Those not receiving β-blockers had a relatively longer mean DFS (10.8 vs. 9.7 years), although the difference did not reach statistical significance (p = 0.651). When the survival analysis was adjusted for age, tumor stage, hormone receptor status and HER2 status, the results remained unaltered, suggesting that β-blocker use did not significantly improve overall DFS (HR, 0.849; 95% CI, 0.537-1.343; p = 0.485). Conclusion: Our findings failed to confirm previous results indicating a potential antitumor effect of β-blockers.

BackgroundThe primary end point of our study was to test whether the concurrent use of a statin is related to a lower risk of recurrence and increased relapse-free survival in patients with early breast cancer.Materials and methodsWe reviewed 610 female patients with stage I, II, or III breast cancer who had been surgically treated and who had subsequently received at least adjuvant chemotherapy in order to prevent recurrence.ResultsAmong the 610 patients with breast cancer, 83 (13.6%) were receiving a statin on a chronic basis for other medical purposes. Overall, statin users displayed longer mean relapse-free survival (16.6 vs 10.2 years, P=0.028). After data had been adjusted for patient and disease characteristics, statin users maintained a lower risk of recurrence. This favorable outcome in statin users was particularly evident when we included only younger patients in the analysis (20 vs 10 years, P=0.006).ConclusionStatins may be linked to a favorable outcome in early breast cancer patients, especially in younger age-groups.

Background/Aim: The role of FOXP3+ Tregs and CD8+ T-cells in different stages and subtypes of breast carcinoma (BC) is yet to be fully defined, mainly because of methodological variations between studies. The aim of this study was to assess FOXP3+ and CD8+ intratumoral stromal TILs (sTILs) by a standardized method, in order to discern differences between the histological subtypes and BC stage and evaluate the applicability of the method. Patients and Methods: FOXP3+ and CD8+ sTILs were studied immunohistochemically in 207 BCs and counted on digital images, amounting to a standard stromal area of a 10×10 grid on ×40 magnification. The results were correlated with clinicopathological features and outcomes. Results: Tregs and CD8+ TILs were more abundant in HER2+ BCs (p=0.02, p=0.007, respectively), estrogen receptor (ER)-BCs (p<0.001, for both cell types), and triple-negative BCs (TNBCs) (p=0.01, p=0.006, respectively). Tregs and CD8+ TILs were associated with high grade (p<0.001 and p=0.002, respectively) and high Ki67 index (p<0.001, for both cell types). Lower CD8/FOXP3 ratio was associated with node metastases (p=0.007). Node metastases and advanced stage paralleled with decreased CD8+ sTILs (p=0. 023, p=0.019, respectively). In the entire group and in ER-BCs, CD8+ TILs were associated with favorable distant metastasis-free survival (p=0.021, p<0.001, respectively), disease-free survival (p=0.022, p<0.001, respectively) and breast cancer specific survival (BCSS) (p=0.022, p=0.005). In ER-BCs, Tregs were associated with favorable BCSS (p=0.02). Conclusion: Tregs and CD8+ TILs are higher in early-stage TNBCs and HER2+ BCs and diminish with progression to advanced stages. The findings provide support for immunotherapeutic manipulation of TILs, particularly in early stages of these BC subtypes. The evaluation methodology can be easily implemented for standardization of immunohistochemically-detected TILs.

Glucocorticoids act through the glucocorticoid receptor (GR) and exert pleiotropic effects in different cancer types. In prostate cancer cells, GR and androgen receptor (AR) share overlapping transcriptomes and cistromes. Under enzalutamide treatment, GR signaling can bypass AR activation and promote castration resistance via the expression of a subset of AR-target genes. However, GR-dependent growth under enhanced antiandrogen inhibition occurs only in a subset of primed cells. On the other hand, glucocorticoids have been used successfully in the treatment of prostate cancer for many years. In the context of AR signaling, GR competes with AR for DNA-binding and has the potential to halt the proliferation rate of prostate cancer cells. Their target genes overlap by <50% and they execute unique functions in vivo. In addition, even when AR and GR upregulate the same transcriptional target gene, the effect might not be identical in magnitude. Besides being able to drive tumor proliferation, GR is also a key player in prostate cancer cell survival. Stimulation of GR activity can undermine the effects of enhanced antiandrogen treatment, chemotherapy and radiotherapy. GR activation in prostate cancer can increase prosurvival gene expression. Identifying the full spectrum of GR activity will inform the optimal use of glucocorticosteroids in prostate cancer. It will also determine the best strategies to target the protumorigenic effects of GR.

Numerous studies have firmly established the role of ion channels in essentially all basic cellular functions. Apart from their role in ion transport, they can form macromolecular complexes with adhesion proteins, and signaling molecules. Ion channels are not only responsible for cellular electrogenesis and excitability, but they also regulate the necessary conditions for tissue homeostasis, such as differentiation, proliferation and apoptosis.Although cancer is not officially classified as a channelopathy, it has been increasingly recognized that ion channel aberrations play an important role in virtually all cancer types.Ion channels can exert pro-tumorigenic activities due to genetic or epigenetic alterations, or as a response to molecular signals, such as growth factors, hormones, etc. Prostate cancer is the second leading cause of cancer-related death in men in the United States. Increasing evidence suggests that ion channels and pumps play a critical role in the regulation of prostate cancer cell proliferation, apoptosis evasion, migration, epithelial-to-mesenchymal transition and angiogenesis. There is also evidence suggesting that ion channels might play a role in treatment failure in prostate cancer. Hence, they represent promising targets for diagnosis, staging and treatment. Here, the role of major types of ion channels involved in the development and progression of prostate cancer were reviewed. Identifying the

Background:The primary end point of our study was to test whether the concurrent use of a statin is related to a lower risk of recurrence and increased relapse-free survival in patients with early breast cancer. Materials and methods:We reviewed 610 female patients with stage I, II, or III breast cancer who had been surgically treated and who had subsequently received at least adjuvant chemotherapy in order to prevent recurrence. Results: Among the 610 patients with breast cancer, 83 (13.6%) were receiving a statin on a chronic basis for other medical purposes. Overall, statin users displayed longer mean relapsefree survival (16.6 vs 10.2 years, P=0.028). After data had been adjusted for patient and disease characteristics, statin users maintained a lower risk of recurrence. This favorable outcome in statin users was particularly evident when we included only younger patients in the analysis (20 vs 10 years, P=0.006). Conclusion: Statins may be linked to a favorable outcome in early breast cancer patients, especially in younger age-groups.

Although prostate cancer is a major cause of cancer-related mortality worldwide, most patients will have a relatively indolent clinical course. Contrary to most other types of cancer, even the diagnosis of locally advanced or metastatic disease is not always lethal. The present review aimed to summarize what is known regarding the underlying mechanisms related to the indolent course of subsets of prostate cancer, at various stages. The data suggested that no specific gene alteration by itself was responsible for carcinogenesis or disease aggressiveness. However, pathway analysis identified genetic aberrations in multiple critical pathways that tend to accumulate over the course of the disease. The progression from indolence into aggressive disease is associated with a complex interplay in which genetic and epigenetic factors are involved. The effect of the immune tumor microenvironment is also very important. Emerging evidence has suggested that the upregulation of pathways related to cellular aging and senescence can identify patients with indolent disease. In addition, a number of tumors enter a long-lasting quiescent state. Further research will determine whether halting tumor evolution is a feasible option, and whether the life of patients can be markedly prolonged by inducing tumor senescence or long-term dormancy.