Role of Epstein-Barr Virus in Breast Cancer: Correlation with Clinical Outcome and Survival Analysis.

Background: Breast cancer is the most prevalent cancer among women worldwide. The potential involvement of Epstein-Barr virus (EBV) in breast cancer pathogenesis has been a subject of debate, but its correlation with clinical outcomes remains uncertain. Methods: In this study, we collected 276 pathologically confirmed breast cancer tissue samples from the tissue bank of MacKay Memorial Hospital and the National Health Research Institutes in Taiwan. DNA was extracted from frozen tissue using The QIAamp DNA Mini Kit. The Taqman quantitative PCR method was employed to assess the EBV copy number per cell in these samples, using NAMALWA cells as a reference. We performed statistical analyses, including 2 × 2 contingency tables, Cox regression analysis, and Kaplan-Meier survival curves, to explore the association between clinicopathologic factors and survival outcomes in breast cancer patients. We analyzed both relapse survival, which reflects the period patients remain free from cancer recurrence post-treatment, and overall survival, which encompasses all-cause mortality. Results: Our results revealed a significant association between EBV status and relapse survival (hazard ratio: 2.75, 95% CI: 1.30, 5.86; p = 0.008) in breast cancer patients. However, no significant association was found in overall survival outcomes. Additionally, we observed significant associations between ER status and tumor histologic grade with both overall and relapse survival. Patients with EBV-positive tumors exhibited higher recurrence rates compared to those with EBV-negative tumors. Furthermore, we noted significant correlations between EBV status and HER-2 (p = 0.0005) and histological grade (p = 0.02) in our cohort of breast cancer patients. Conclusions: The presence of EBV in breast cancer tumors appears to exert an impact on patient outcomes, particularly concerning recurrence rates. Our findings highlight the significance of considering EBV status as a potential prognostic marker in breast cancer patients. Nonetheless, further research is essential to elucidate the underlying molecular mechanisms and develop novel therapeutic approaches.

Massive metastasis of breast cancer to female genital organs.

OBJECTIVE: Breast cancer metastasis to the female genital tract is rare, and the ovaries are the most frequent site of extragenital cancer metastasis. The uterus and cervix have been rarely reported as the site of metastasis. CASE REPORT: A 57-year-old woman diagnosed with invasive lobular carcinoma of the left breast 2 years prior was undergoing tamoxifen treatment. She presented with a right breast mass and postmenopausal bleeding. Synchronous right breast invasive lobular carcinoma with endometrium metastasis was diagnosed. The metastasis tumor involved the endometrium, myometrium, cervix, ovaries, and fallopian tubes. CONCLUSION: We noted the rarity of massive metastasis of the female genital tract from breast cancer. Gynecological surveillance and prompt evaluation of the endometrium led to timely diagnosis and treatment.

Association between neutrophil-to-lymphocyte ratio and parathyroid hormone in patients with primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is associated with adverse cardiovascular outcomes which may result from an increase in systemic inflammation. Previously we have shown that serum parathyroid hormone (PTH) levels are independently associated with inflammatory indicators. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive, widely available marker of inflammation. In the present study, we aimed to assess the longitudinal changes in NLR before and after parathyroidectomy. MATERIAL AND METHODS: This retrospective study included 95 patients diagnosed with PHPT who underwent parathyroidectomy between 2006 and 2016. Follow-up complete blood counts were available in 31 patients. RESULTS: At diagnosis, 43 (45%) patients presented with overt clinical symptoms and had higher serum calcium and PTH levels. Preoperative NLR was positively correlated with total white blood cell count (p = 0.001), serum calcium (p = 0.001), and PTH level (p = 0.013). The NLR was not associated with sex, age, comorbidities, or parathyroid weight. Among patients who were cured of PHPT, the median NLR decreased from 2.26 to 1.77 after parathyroidectomy (p = 0.037). There was no difference in hemoglobin, total white blood cells, or platelet count before and after surgery. CONCLUSIONS: We found a positive correlation of preoperative NLR with calcium and PTH levels in PHPT patients. After curative parathyroidectomy, NLR modestly decreased without changes in other hematological parameters.

A Single Institution Experience of Incorporation of Cisplatin into Adjuvant Chemotherapy for Patients With Triple-Negative Breast Cancer of Unknown BRCA Mutation Status.

The clinical benefit of adding platinum to adjuvant chemotherapy for patients with triple-negative breast cancer (TNBC) has not been well investigated, although it was associated an improved response rate in neoadjuvant setting. We retrospectively analyzed the time to tumor progression (TTP) and overall survival (OS) of patients with resected stage I-III TNBC who were treated with or without cisplatin-containing chemotherapy (CisCT or noCisCT) during 2004 and 2010. Of 129 patients, 25 received CisCT. In univariate analysis, the mean TTP for CisCT and noCisCT was 4.42 and 5.88 years, respectively (P = .004). The mean OS for CisCT and noCisCT was 6.76 and 9.63 years, respectively (P = .24). After adjusting for other clinicopathologic factors, only clinical stage II/III disease was independently associated with worse OS. The adjusted hazard ratio for CisCT was 1.48 (P = .46) and was not statistically significant. In this small retrospective study, adding cisplatin to adjuvant chemotherapy for early TNBC with unknown BRCA mutation status did not benefit OS.

Multi-center study on patient selection for and the oncologic safety of intraoperative radiotherapy (IORT) with the Xoft Axxent® eBx® System for the management of early stage breast cancer in Taiwan.

BACKGROUND: In this multi-center study, we report the patient selection criteria for and preliminary oncologic outcomes associated with intraoperative radiotherapy (IORT) delivered by the Xoft Axxent® eBx® system for early-stage breast cancer in Taiwan. METHODS: Patients with early breast cancer in Taiwan received breast conserving surgery and received IORT with Xoft Axxent® eBx® System during 2013-2015 was search from database of Taiwan IORT study cooperative group (T-IORTSCG). Patients' clinicopathologic characteristics and early post-operative results were collected and reported. RESULTS: During the study period, 26 hospitals in Taiwan performed a total of 261 Xoft IORT procedures for breast cancer. The mean age of them was 52.9 ± 9.8 years (37-72), and tumor size was 1.5 ± 0.8 cm (0.1-4.2 cm) for invasive cancer and 1.2 ± 0.8 cm (range, 0.2-3.0 cm) for ductal carcinoma in situ (DCIS) lesions. Lymph node metastasis was found in 6 (2.3%) patients. The patients received IORT in Taiwan differed markedly from those used in the ELIOT and TARGIT-A studies. Specifically, patients selected for IORT in Taiwan tended to be younger, their tumors tended to be larger and the prevalence of lymph node metastasis tended to be lower. Among these 261 patients, 8 (3.1%) patients required whole breast radiotherapy. During a mean follow up of 15.6 months, locoregional recurrence was observed in 2 (0.8%) patients. CONCLUSION: In real world experience, patients received IORT differed quite significantly with criteria formulated by trials. The preliminary results of IORT in Taiwan showed it is well acceptable by patients and clinicians.

Habitual sleep-wake behaviors and lifestyle as predictors of diurnal cortisol patterns in young breast cancer survivors: a longitudinal study.

OBJECTIVE: This study aimed to identify predictors of changes in diurnal cortisol patterns during the 8-month follow up period for young breast cancer survivors. Among the potential predictors were tumor size, lymph node metastasis, changes in sleep problems, habitual time of awakening and bedtime, physical activity levels, body mass index (BMI), and depressive levels across 8 months. METHODS: The participants were 62 breast cancer women who were aged 40 years and below, and had completed active breast cancer treatment. The longitudinal data were collected at four points: baseline assessment (T0) and three follow-ups after baseline: T1 (in the 2nd month), T2 (in the 5th month), and T3 (in the 8th month). The participants collected their salivary cortisol at home at six time points: upon waking, 30 and 45min after waking, and at 1200h, 1700h, and 2100h. They also completed several questionnaires: the Medical Outcomes Study Sleep scale; the Beck Depression Inventory-II, physical activity levels on a 10-point scale, time of going to bed, time of awakening, and total sleep hours. RESULTS: This study found that the main predictors of changes toward flatter diurnal cortisol patterns during the 8-month follow ups were greater tumor sizes, increases of BMI scores, and habitually later times of awakening. CONCLUSIONS: While greater tumor sizes represent biological vulnerability of disruption of cortisol circadian rhythm, maintaining an appropriate BMI and good sleep habits could be a protective factor for normal cortisol regulation, which likely helps to reduce early mortality in young breast cancer survivors.

Monitoring patient-centered outcomes through the progression of breast reconstruction: a multicentered prospective longitudinal evaluation.

Studies have shown that having breast reconstruction has a positive influence on patient satisfaction and health-related quality of life (HRQoL) at the conclusion of treatment. However, no study has critically evaluated changes to these patient-reported outcomes during the process of undergoing breast reconstruction. This study was to prospectively evaluate changes to patient-centered metrics through the progression of breast reconstruction. An IRB-approved prospective, multi-institutional study was performed for all patients undergoing breast reconstruction between 2009 and 2011. The Breast-Q reconstruction questionnaire was used for evaluation of HRQoL and was administered at five intervals in the perioperative period. Longitudinal evaluation was performed to assess changes to HRQoL metrics during this perioperative interval. One hundred and ten patients were enrolled, and 100 patients (91.9 %) completed appropriate follow-up. Preoperative HRQoL scores were higher in patients electing to forgo reconstruction (P < 0.004), while postoperative HRQoL scores consistently deteriorated at multiple time points following mastectomy as compared to reconstructed patients. On subgroup analysis, results indicated lower initial HRQoL scores in delayed reconstruction (P < 0.05) as compared to immediate reconstruction. These scores did, however, merge at approximately 9 months postoperatively. Changes to HRQoL outcomes occur through progression of breast reconstruction. Within the first year of surgery, early decreases are mirrored by significant increases at later time points above baseline levels when evaluating most forms of reconstruction. Choosing against reconstruction will likely result in continued deterioration of HRQoL for patients undergoing cancer surgery, but steady improvements can be expected if delayed reconstruction is chosen.

The efficacy of acupoint stimulation for the management of therapy-related adverse events in patients with breast cancer: a systematic review.

The aim of the present study was to scrutinize the evidence on the use of acupoint stimulation for managing therapy-related adverse events in breast cancer. A comprehensive search was conducted on eight English and Chinese databases to identify clinical trials designed to examine the efficacy of acupressure, acupuncture, or acupoint stimulation (APS) for the management of adverse events due to treatments of breast cancer. Methodological quality of the trials was assessed using a modified Jadad scale. Using pre-determined keywords, 843 possibly relevant titles were identified. Eventually 26 papers, 18 in English and eight in Chinese, satisfied the inclusion criteria and entered the quality assessment stage. The 26 articles were published between 1999 and 2008. They assessed the application of acupoint stimulation on six disparate conditions related to anticancer therapies including vasomotor syndrome, chemotherapy-induced nausea and vomiting, lymphedema, post-operation pain, aromatase inhibitors-related joint pain and leukopenia. Modalities of acupoint stimulation used included traditional acupuncture, acupressure, electroacupuncture, and the use of magnetic device on acupuncture points. Overall, 23 trials (88%) reported positive outcomes on at least one of the conditions examined. However, only nine trials (35%) were of high quality; they had a modified Jadad score of 3 or above. Three high quality trials revealed that acupoint stimulation on P6 (NeiGuang) was beneficial to chemotherapy-induced nausea and vomiting. For other adverse events, the quality of many of the trials identified was poor; no conclusive remarks can be made. Very few minor adverse events were observed, and only in five trials. APS, in particular acupressure on the P6 acupoint, appears beneficial in the management of chemotherapy-induced nausea and vomiting, especially in the acute phase. More well-designed trials using rigorous methodology are required to evaluate the effectiveness of acupoint stimulation interventions on managing other distress symptoms.

Effect of cholinergic denervation on hepatic fibrosis induced by carbon tetrachloride in rats.

Various factors involved in the development of liver fibrosis, including hepatic stellate cells (HSCs), cholinergic nervous activity and fibrogenetic cytokines. The present study aims to investigate the role of cholinergic regulation in the promoting of liver fibrogenesis relating to bone morphogenetic protein-6 (BMP-6) and/or transforming growth factor-beta1 (TGFbeta1). We treated carbon tetrachloride (CCl(4)) into rats for eight weeks to induce liver fibrosis and arranged these rats for cholinergic denervation, hepatic branch vagotomy or atropine administration. Acetylcholinesterase (AChE) staining showed the distribution of cholinergic nerve around fibrosis scaring septa. The immunohistochemical staining for alpha smooth muscle actin (alphaSMA) indicated the less HSCs in CCl(4) treated rat liver with cholinergic denervation as compared to the sham-operated CCl(4) treated rats. It seems that cholinergic nerve not only innervates around the fibrosis area but also promotes HSCs. We also detected TGFbeta1 and BMP-6 expressions using RT-PCR and immunohistochemistry. The obtained results show that cholinergic denerveration decreases BMP-6 and TGF-beta1 expressions in CCl(4) induced liver fibrosis of rats. In conclusion, cholinergic nerve may influence HSCs in addition to the lowering of BMP-6 and TGF-beta1 gene expressions to modify liver fibrosis.