Long-Noncoding-RNA HOTAIR Upregulation is Associated with Poor Breast Cancer Outcome: A Systematic Review and Meta Analysis.

BACKGROUND: Breast cancer is the most frequent cancer among women worldwide with significant disproportionate mortality rates in developing countries. Although clinical management of breast cancer has been immensely improved, refinement in the prognostic and recurrent markers is still needed. Long non-coding RNAs (lncRNA) HOTAIR has recently been associated with poor outcome and is potentially used as a prognostic marker in breast cancer. METHODS: We comprehensively reviewed studies evaluating lncRNA HOTAIR in association with overall and disease-free survivals in breast cancers. Systematic searches were performed in Pubmed, ProQuest, ScienceDirect, Scopus, Google Scholar, Semantic Scholar, Springer, Nature, Sage Journals, and Wiley databases using combination keywords "long non-coding RNA," "lncRNA," "HOX transcript antisense RNA," "HOTAIR," "breast can-cer," "carcinoma mammae," "prognosis," and "survival." Risk of bias score was used to assess quality of studies, I2 test was conducted to assess heterogeneity. Meta-analysis was performed to compare HOTAIR expression with breast cancer survival rates using STATA v.17 software. RESULTS: Of the total 1,504 screened studies, seven studies were included in the meta-analysis involving 533 patients. High expression of HOTAIR was associated with poor survival rates (pooled HR: 1.69; 95%CI: 1.11-2.59; p=0.015), shorter overall survival (OS) (pooled HR: 1.33; 95%CI: 0.78-2.26; p=0.455), poor disease-free survival (DFS) (pooled HR: 2.40; 95%CI: 1.63-3.53; p<0.001), poor distant metastatic-free survival (MFS) (HR: 1.75; 95%CI: 1.13-2.71; p=0.012). In addition, overexpression of HOTAIR was associated with positive lymph node infiltration (pooled OR: 2.38; 95%CI: 0.53-10.69; p=0.26) and ductal type cancer (pooled OR: 3.27; 95%CI: 1.15-9.30; p=0.03). CONCLUSION: Upregulation of lncRNA HOTAIR is associated with worse DFS aand MFS that can potentially be used as a prognostic marker in breast cancer patients.

Prognostic Value of Vimentin in Triple Negative Breast Cancer Patients Depends on Chemotherapy Regimen and p53 Mutant Expression.

Purpose: To determine the prognostic value of vimentin in triple negative breast cancer (TNBC) patients, specifically in relation to chemotherapy regimen and p53 mutant expression. Patient and Methods: We retrospectively analyzed the association of pre-treatment tumor expression of vimentin with 48-month overall survival (OS) of 72 all stages TNBC patients diagnosed between 2014 and 2018 in relation to chemotherapy regimen and expression of p53 mutant. Vimentin and p53 mutant expressions were examined using immunohistochemistry. Analysis was conducted on all patients collectively, then repeated on two cohorts divided according to the chemotherapy regimen. Sub-analysis was performed to determine the effect of p53 mutant expression on the prognostic value of vimentin. Results: Vimentin was expressed in 43.1% of patients and was not associated with clinicopathologic characteristics. Vimentin was associated with improved 48-month OS in all patients in univariate analysis but not significant in multivariate analysis. When analyzed according to chemotherapy regimen, vimentin was independently associated with improved 48-month OS in patients receiving non-platinum-based chemotherapy (80% vs 15.8%; HR: 0.17, 95% CI: 0.05-0.58, p: 0.005). Other independent prognostic factors include T (HR: 6.18, 95% CI: 1.38-27.7, p: 0.017) and M (HR: 5.64, 95% CI: 1.2-26.33, p: 0.028). On subanalysis, vimentin was significantly associated with improved 48-month OS in patients expressing p53 mutant (69.2% vs 22.2%, p: 0.006) but was not significant in patients not expressing p53 mutant. Conclusion: Vimentin expression was independently associated with improved 48-month OS in TNBC patients treated with non-platinum-based chemotherapy. Expression of p53 mutant significantly affected the prognostic value of vimentin.

MicroRNA Gene Signature for Predicting Mechanisms in Nasopharyngeal Carcinoma: A Case Study on the Potential Application of Circulating Biomarkers.

BACKGROUND AND AIM: Nasopharyngeal Carcinoma (NPC) is an upper respiratory tract cancer prevalent in Southeast Asia and related to chronic EBV infection. microRNAs (miRNAs) regulate gene expression implicated in NPC's carcinogenesis. However, this circulating RNA molecule's role and clinical utility remain unknown. Therefore, this study examined the circulation of miRNAs and their association with clinical data. METHODS: 160 plasma samples of NPC and 80 non-tumor samples were extracted to evaluate and validate the gene expressions. Quantification expression was performed using relative quantification of qPCR analysis level expression methods. The intrinsic cellular roles involving biological signaling in NPC's oncogenesis using Ingenuity Pathways Analysis (IPA) were also used. RESULTS: The results of the quantification significance profiling of NPC samples revealed decreased miR- 29c-3p (fold change 1.16; p<0.05) and increased 195-5p expression (fold change 1.157; p<0.05). Furthermore, the validation of hsa-miR-29c-3p expression on plasma NPC with known tumor vs. non-tumor and significant changes was also performed using a fold change of 4.45 (medians of 31.45 ± 1.868 and 24.96 ± 1.872, respectively; p<0.0005). miR-29c had a 2.14 fold change correlated with T primary status with a median of 31.99±1.319 and 31.35±2.412, respectively (p<0.05). Stage status with fold change 1.99 also had median levels of 31.98±1.105 and 31.21 ± 2.355, respectively (p-value <0.05). Furthermore, the node's status for the lower expression of miR-29c with fold change 1.17 had median levels of 32.78 ± 2.221 and 31.33 ± 1.689, respectively (p-value of 0.7). Bioinformatics analysis established the roles and functions of miR-29 in NPC progression, cell death and survival, cellular development, cellular function, and cell maintenance by inhibiting COL4A, PI3K, VEGFA, JUN, and CDK6. CONCLUSION: Overall, we conclude that decreased miR-29c expression is associated with poor clinical status and might inhibit NPC's five target genes.

The Association between Abdominal Obesity, Metabolic Syndrome and Survival Outcomes in Patients with Breast Cancer.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been linked to the risk of developing certain cancers. This study aimed to analyze the association between obesity markers, MetS and survival outcomes of patients with breast cancer. METHODS: This study retrospectively investigated patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-), nonmetastatic breast cancer diagnosed between January 2010 and December 2019. Data on clinical conditions, body mass index (BMI), waist-to-hip ratio (WHR), MetS, time of metastasis and death were collected. RESULTS: A total of 223 breast cancer patient records were eligible for analysis. Obesity (BMI ≥ 25) was found in 38.1% of cases. Abdominal obesity measured as WHR ≥ 0.85 was found in 48.9%. Metabolic syndrome was detected in 56.1% of patients and was associated with older age (OR = 2.196, p = 0.005), postmenopausal status (OR = 2.585, p = 0.001), obesity (OR = 5.684, p = 0.001) and abdominal obesity (OR = 2.612, p = 0.001). Obesity was not associated with poor disease-free survival (DFS) or overall survival (OS), while abdominal obesity was modestly associated with poor DFS (HR = 1.539, p = 0.083) and OS (HR = 3.117; p = 0.019). Multivariate analysis revealed that WHR ≥ 0.85 was independently associated with unfavorable DFS (HR = 1.907, p = 0.027). Patients with MetS had a similar survival rate to those with normal metabolism. CONCLUSION: In Indonesian women with HR+/HER2- breast cancers, obesity and MetS were not associated with poor survival outcomes. The abdominal obesity marker (WHR) was more accurate in predicting unfavorable DFS.

The effect of NPWT in wound healing and bacterial count on deep dermal burn injury model: An experimental study.

Background: Sepsis is one of the main causes in burn victim's mortality. The use of negative pressure wound therapy (NPWT) provides an ideal environment to accelerate wound healing. We compare the use of normal saline (NS), intermittent NPWT, continuous NPWT and silver sulfadiazine in wound healing process. Method: This study involved 6 Yorkshire pigs; each pig was induced with 20 burns on the flank area. Burns were divided into 4 treatment groups: NS gauze, intermittent NPWT, continuous NPWT, and silver sulfadiazine dressing. Burns were evaluated on day 1,3,7,14, and 21 for its morphology and bacterial colonization and on day 14 and 21 for the remaining burn surface area. Result: Wound that received NPWT therapy appeared better in both granulation and crust formation. Remaining burn surface area (mm2) on day 14 in NS group, intermittent NPWT, continuous NPWT, and silver sulfadiazine were 107.43 ± 83.43, 178.07 ± 74.83, 146.10 ± 69.1, 126.03 ± 83.22, respectively(p = 0.457); on day 21 in NS group, intermittent NPWT, continuous NPWT, and silver sulfadiazine were 13.16 ± 16.86, 59.49 ± 20.72, 54.79 ± 46.59, 48.95 ± 39.84, respectively(p=0.169). There were no significant differences in each treatment group bacterial colonization(p>0.05). There were no significant correlation between bacterial colonization and remaining burn surface area (p>0.05). Conclusion: While morphologically, the wound in NPWT treatment groups appeared better in granulation and crust formation, the remaining wound surface area and the number of bacterial colonization were not significantly difference compared to standard therapy (silver sulfadiazine and NS gauze). There were no significant correlation between the amount of bacterial colonization and remaining wound surface area on every treatment group.

Cost-Effectiveness Analysis of Two Chemotherapy Regiments FAC vs. Taxane for Operable Breast Cancer Patients in Indonesia.

BACKGROUND: Breast cancer is the deadliest cancer among women worldwide including Indonesia. Both FAC and Taxane-based chemotherapies are often used for patients with early node-positive breast cancer. However, the study regarding the cost-effectiveness of those regiments is still rare. This study aims to analyze the cost-effectiveness of Taxane versus FAC in the Indonesia setting. METHODS: Twenty-four patients with stage I-IIIA breast cancer who had received surgery, FAC or Taxane-based adjuvant chemotherapy, and radiation were included in this study. Health-related quality of life was assessed using INA-BCHRQoL. INA-BCHRQoL was mapped to the EuroQoL 5D (EQ-5D) index calculator to get the utility score. All direct cost was retrieved from electronic medical records and hospital information system. Whereas, a questionnaire was designed to collect information about society cost from patients. ICER was counted to summarize the cost-effectiveness of two chemotherapy regiments (Taxane versus FAC). A sensitivity analysis was done to assess the uncertainty result. RESULTS: The results showed there was no significant difference between the score of quality of life and utility in respondents who received FAC chemotherapy and Taxane-based chemotherapy. However, in terms of cost, Taxane was 6.5 times higher than the FAC group per patient for chemotherapy drugs only. Moreover, the total cost of treatments in Taxane-based chemotherapy was approximately 3.7 times more costly than the counterpart in the FAC arm (p=0.000). Taxane-based chemotherapy dominated with ICER IDR 765.213.092 per QALY gained. Overall, FAC was found more cost-effective compared to the Taxane regiment. CONCLUSION: FAC represents the value of money compared to Taxane-based for breast cancer patients with stage I-IIIA in Indonesia.

Chemopreventive Effect of Dietary Maranta arundinacea L. Against DMBA-Induced Mammary Cancer in Sprague Dawley Rats Through the Regulation of Autophagy Expression.

BACKGROUND: Breast cancer prevention still needs to be improved. Calorie restriction is thought to prevent breast cancer through the induction of autophagy. Maranta arundinacea L. (MA) has the potential for calorie restriction because it contains high fiber. This research aimed to observe the effect of dietary MA against dimethylbenz(a)anthracene (DMBA)-induced mammary cancer in Sprague Dawley rats related to autophagy. METHODS: Twenty-five Sprague Dawley rats were randomly divided into five groups: 1) control group without DMBA-induced with a standard diet, 2) 20 mg/kg BW of DMBA two times a week for five weeks with a standard diet, 3) DMBA and diet modification with 30% of MA, 4) DMBA and diet modification with 45% of MA, and 5) DMBA and diet modification with 60% of MA. Examination of the nodule was conducted once every week for 22 weeks. Breast tissue/tumor examination underwent histology examination with hematoxylin-eosin. Examinations of immunohistochemical staining against Beclin1, LC3B, and SQSTM1 were conducted to reveal autophagy. The difference of autophagy protein expression was analyzed using One way ANOVA with 95% confidence level and significance set as p<0.05. RESULTS: Cancer was detected in four rats of DMBA standard diet, two rats of 30% MA, one rat of 45% MA. No cancer was detected in the rats of control and rats with 60% of MA group. The Beclin1 expressions showed that the 60% of MA group had the highest score (2.5±0.52) followed by the 45% of MA group (1.87±0.49), control group (1.77±0.11), 30% of MA group (1.28±0.75), and DMBA with standard diet had the lowest score (1.28±0.91). The difference of Beclin1 expressions was statistically significant (p-value=0.03). However, the difference of the LC3B expressions (p-value=0.11) and SQSTM1 expressions (p-value=0.225) were not statistically significant. CONCLUSION: Dietary modifications with MA potentially prevent breast cancer and induce initiation of autophagy.

Predictors of the conservative management outcomes in patients with lumbar herniated nucleus pulposus: A prospective study in Indonesia.

BACKGROUND: The objective of this study was to identify the predictors of the conservative management outcomes in patients with lumbar herniated nucleus pulposus (HNP). METHODS: A prospective study was conducted between June 2010 and April 2012 in Banda Aceh, Indonesia. Clinical and baseline neurologic examinations such as passive straight leg raising test (SLRT), cross SLRT, and patellar and Achilles reflexes were assessed prior to the conservative management. The patients were evaluated at 2nd, 4th, 8th, 12th and 24th week following commencement of the conservative management. RESULTS: We recruited and followed 171 HNP patients of which 35.7% of them had good outcome. At univariate analysis, patients with more than 12 months duration of complaint, those with dominant radicular pain, severe pain intensity (visual analogue scale 7-10), positive SLRT, positive cross SLRT, and reduced motor power of knee extensors (muscle strength grade 1-4), were associated with poor outcome. Multivariate analysis suggested that patients with dominant radicular type of pain were likely to had poor outcome compared to those with dominant back pain (odd ratio (OR) 10.57 with 95% confidence interval (CI) 1.15-96.93). Patients with reduced motor power of knee extensors also had a higher chance to have poor outcome compared to those who were normal (OR: 10.57; 95% CI: 1.15-96.93). CONCLUSION: Type of pain and the strength of lower extremities could be able to predict the failure of conservative management in patients with lumbar disc herniation. However, further studies with the bigger sample size are warrant to validate our results.

ESR1 PvuII polymorphism: from risk factor to prognostic and predictive factor of the success of primary systemic therapy in advanced breast cancer.

BACKGROUND: The ESR1 gene encodes Estrogen Receptor alpha (ERα), which plays a role in the tumourigenesis of breast cancer. A single nucleotide polymorphism (SNP) in intron 1 of this gene called ESR1 PvuII (rs2234693) has been reported to increase the risk of breast cancer. This study aimed to investigate the ESR1 PvuII polymorphism as a prognostic and predictive factor guiding the choice of therapy for advanced breast cancer. METHODS: This retrospective study was conducted in 104 advanced breast cancer patients at Dharmais Cancer Hospital from 2011 to 2018. The ESR1 PvuII polymorphism was analysed by Sanger sequencing of DNA from primary breast tumour samples. RESULTS: The percentages of patients with ESR1 PvuII genotypes TT, TC, and CC were 42.3, 39.4, and 18.3%, respectively. Looking at prognosis, patients with ESR1 PvuII TC + CC had shorter overall survival than those with the TT genotype [HR = 1.79; 95% CI 1.05-3.04; p = 0.032]. As a predictive marker, TC + CC was associated with shorter survival (p = 0.041), but TC + CC patients on primary hormonal therapy had a median overall survival longer than TC + CC patients on primary chemotherapy (1072 vs 599 days). CONCLUSION: The ESR1 PvuII TC + CC genotypes confer poor prognosis in advanced breast cancer, but these genotypes could be regarded as a good predictor of the therapeutic effect of hormonal treatment.

Fatty Liver in Hormone Receptor-Positive Breast Cancer and Its Impact on Patient's Survival.

PURPOSE: Long-term estrogen inhibition may cause fatty liver disease (non-alcoholic fatty liver disease; NAFLD) among other adverse conditions such as osteoporosis, climacteric symptoms, thromboembolism, dyslipidemia, and metabolic syndrome. The prevalence of NAFLD among breast cancer patients ranges from 2.3%-45.2%. This study aimed to determine the risk factors for newly developed NAFLD among breast cancer patients after hormonal treatment and whether it influences survival outcomes. METHODS: This retrospective study investigated hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-), nonmetastatic breast cancer patients diagnosed between January 2010 and December 2018. All patients received adjuvant hormonal treatment for at least 6 months. Clinical data on metabolic profile indicators such as body mass index (BMI), waist circumference, serum cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), diabetes, and presence of metabolic syndrome (MetS) were collected. In total, 160 eligible patients with complete covariate data and survival follow-up were included. RESULTS: NAFLD was diagnosed in 35% of patients. There were significant associations of being overweight (BMI ≥ 25 kg/m²), waist circumference > 80 cm, triglycerides ≥ 150 mg/dL, HDL-C ≤ 50 mg/dL, LDL-C < 150 mg/dL, and presence of MetS with the development of NAFLD. However, unlike other factors, MetS and HDL-C were not independently associated with NAFLD. Patients with breast cancer who developed NAFLD had longer disease-free survival (DFS). The median DFS was not reached in the NAFLD group, whereas it was 59.3 (45.6-73.0) months in the non-NAFLD group. No worsening of overall survival was observed in patients with breast cancer and NAFLD. CONCLUSION: The development of NAFLD during treatment in patients with HR+/HER2- breast cancer was associated with several independent risk factors: being overweight, waist circumference, triglycerides, and LDL-C. Interestingly, breast cancer patients with NAFLD during treatment had longer DFS than those without NAFLD.

Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer.

OBJECTIVE: The association between PD-1, PD-L1, and PD-L2 expression and prognosis has been extensively studied in various cancers but remained controversial in breast cancer. Besides, little is known about the prognostic value of PD-1, PD-L1, and PD-L2 upregulation or downregulation following systemic therapy (chemotherapy and hormonal therapy) in breast cancer. Therefore, we aim to investigate the change of PD-1, PD-L1, and PD-L2 expression in mRNA level after primary systemic therapy in breast cancer patients and its clinical implications. METHODS: Expression of PD-1, PD-L1, and PD-L2 mRNA were measured before-after chemotherapy and hormonal therapy with real-time PCR in 80 advanced breast cancer patients. The correlation between alteration of PD-1, PD-L1, and PD-L2 expression and clinicopathological characteristics as well as overall survival was also statistically analyzed. RESULTS: Chemotherapy and hormonal therapy altered PD-1, PD-L1, and PD-L2 expression in breast cancer with most patients have an increase expression. As much as 57.1%, 62.9% and 60% patients have an increase PD-1, PD-L1, and PD-L2 expression after chemotherapy, while 60%, 60%, and 64% patients have an increase PD-1, PD-L1, and PD-L2 expression after hormonal therapy. Alteration of PD-1, PD-L1, and PD-L2 expression was not correlated with all clinicopathological characteristics. Increase in PD-1, PD-L1, and PD-L2 expression was significantly associated with better OS (p=0.031, p=0.019, and p=0.019 for PD-1, PD-L1, and PD-L2, respectively), which remained significant in multivariate analysis including age, stage, primary systemic therapy, histology grade, subtype and primary tumor histology (HR PD-1 0.5 (95% CI 0.28-0.88) p=0.031; HR PD-L1 0.43 (95% CI 0.24-0.8) p=0.019; HR PD-L2 (95% CI 0.24-0.87) p=0.019).  Conclusion: Expression of PD-1, PD-L1, and PD-L2 in breast cancer patients is mostly enhanced after chemotherapy and hormonal therapy, and the enhancement is associated with good OS. This result revealed the potential of measuring PD-1, PD-L1, and PD-L2 mRNA expression in predicting clinical outcome.

Potential prognostic value of PD-L1 and NKG2A expression in Indonesian patients with skin nodular melanoma.

OBJECTIVE: Biomarker mRNA levels have been suggested to be predictors of patient survival and therapy response in melanoma cases. This study aimed to investigate the correlations between the mRNA expression levels of PD-L1 and NKG2A in melanoma tissue with clinicopathologic characteristics and survival in Indonesian primary nodular melanoma patients. RESULTS: Thirty-one tissue samples were obtained; two were excluded from survival analysis due to Breslow depth of less than 4 mm. The median survival of upregulated and normoregulated PD-L1-patients were 15.800 ± 2.345 and 28.945 ± 4.126 months, respectively. However, this difference was not significant statistically (p = 0.086). Upregulated and normoregulated NKG2A patients differed very little in median survival time (25.943 ± 7.415 vs 26.470 ± 3.854 months; p = 0.981). Expression of PD-L1 and NKG2A were strongly correlated (rs: 0.787, p < 0.001). No clinicopathologic associations with PD-L1 and NKG2A mRNA levels were observed. These results suggest that PD-L1 may have potential as a prognostic factor. Although an unlikely prognostic factor, NKG2A may become an adjunct target for therapy. The strong correlation between PD-L1 and NKG2A suggests that anti-PD-1 and anti-NKG2A agents could be effective in patients with PD-L1 upregulation. The mRNA levels of these two genes may help direct choice of immunotherapy and predict patient outcomes.

Metabolic comorbidities and the association with risks of recurrent metastatic disease in breast cancer survivors.

BACKGROUND: Obesity and other metabolic comorbidities affect over 10% of patients with breast cancer and are closely related with adverse outcomes. Although metabolic comorbidities among breast cancer patients in low- and middle-income countries are suggested to be lower, only a few studies are currently available. Effective management of metabolic comorbidities in cancer patients has been associated with better outcomes. METHODS: Non-metastatic breast cancer patients (N = 1081) treated in our department (2014-2018) were monitored for the presence of high Body Mass Index (BMI), diabetes or glucose intolerance, dyslipidemia, and hypertension and the development of recurrent metastatic diseases during a median follow-up of 3.9 years. RESULTS: Glucose intolerance, hypertension, dyslipidemia, and BMI ≥ 27.7 kg/m2 considered at risk for metabolic comorbidities were found in 26.5, 42.6, 27.7, and 23.3% of breast cancer patients, respectively. Diabetes or glucose intolerance and having both glucose intolerance and dyslipidemia were associated with the risk of recurrent metastatic disease (OR = 1.442, 95%CI = 1.071-1.943, p = 0.016 and OR = 1.495, 95%CI = 1.090-2.049, p = 0.010; respectively). Having three or more metabolic comorbidities was significantly associated with the risk of recurrent metastatic disease (OR = 1.647, 95%CI = 1.139-2.382, p = 0.008) compared to patients without any comorbidity. The metabolic comorbidities were distributed unevenly among breast cancer subtypes. A significant association with recurrent metastatic disease was found in the Luminal B-like subtype. In post-menopausal patients, having more than three comorbidities was associated with a higher risk of recurrent metastatic disease compared to those without any comorbidity (OR = 2.000, 95%CI = 1.035-3.067, p = 0.001). The risks of having three or more metabolic comorbidities were significantly higher in breast cancer survivors who were obese, lived in an urban area, and received hormonal therapy of aromatase inhibitors. CONCLUSION: Metabolic comorbidities were frequently found in breast cancer patients and were associated with higher risks to develop recurrent metastatic disease, particularly in post-menopausal women. Subsequent larger studies are needed to better understand the association of metabolic comorbidities with patients' quality of life and prognosis, and to explore the potential combination of clinical intervention and lifestyle modification in breast cancer survivors to treat as well as reduce their impact.

Concurrent manifestations of Horner's syndrome and esophageal metastasis of breast cancer: case report of a young woman after a period of non-adherence to treatment: a case report.

BACKGROUND: Esophageal involvement and Horner's syndrome are rare manifestations of breast cancer distant metastases that can pose a significant challenge in diagnosis and treatment. In addition to the more aggressive behavior of breast cancer diagnosed in young women, non-adherence to treatment is associated with increased risk of distant metastasis. CASE PRESENTATION: A 36-year-old Javanese woman presented to our institution with dysphagia, hoarseness, and frequent hiccups. In the 6 weeks prior to the current admission, the patient also reported tingling in the neck and shoulder, anhidrosis in the left hemifacial region, and drooping of the upper left eyelid. She was previously managed as tuberculoid laryngitis. Plain X-rays showed burst fractures of the cervical vertebrae and slight pleural effusion. Laryngoscopy revealed bowing of the vocal cords and liquid residue in the vallecula that was reduced upon chin tuck. Esophageal metastasis was confirmed with endoscopy showing thickening of the wall and positive cytology swab with ductal malignant cells. The patient had a history of breast cancer with a period of loss to follow-up of 4 years. CONCLUSIONS: Physicians should consider potential distant metastasis of breast cancer to the esophagus and sympathetic nervous system of the neck particularly in a high-risk woman with presentation of dysphagia and manifestations of Horner's syndrome.

Pre-treatment neutrophil-lymphocyte and platelet-lymphocyte ratios as additional markers for breast cancer progression: A retrospective cohort study.

BACKGROUND: Breast cancer is the most prevalent cancer that causes significant morbidity and loss of productivity. Around a third of all breast cancer patients are potentially develop distant metastases albeit the current implementation of multidisciplinary treatment. A simple but effective marker to predict the risks of cancer progression is very important for clinicians to improve treatment and surveillance. METHODS: We recruited 1083 non-metastatic patients and analyzed the ratios of neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) in relation to progression-free survivals (PFS) and risks of distant metastases. RESULTS: Baseline clinicopathological variables were not significantly different in the pretreatment NLR and PLRs. Using maximum points of sensitivity and specificity of the Receiver Operating Characteristic (ROC) curve, cut-off values were determined 2.8 for NLR and 170 for PLR. Higher NLR was associated with skin and chest wall cancer infiltration (T4, P = 0.0001). Elevated PLR was associated with more advanced stages at diagnosis (P = 0.03). High NLR values were significantly associated with risks of disease progression (OR 1.555, 95% CI: 1.206-2.005, P = 0.001). Patients with high NLR had shorter PFS (34.9 vs 53.5 months, Log-rank test = 0.001) and shorter time to develop recurrent distant metastatic disease (66.6 vs 104.6 months, Log-rank test = 0.027). CONCLUSION: High NLR is significantly associated with higher risk of disease progression and shorter time to develop metastases particularly among breast cancer patients diagnosed in the advanced stages.

Chemotherapy Negates the Effect of SDF1 mRNA to Distant Metastasis and Poor Overall Survival in Breast Cancer Patients.

OBJECTIVE: Investigate the effect of SDF1a, nuclear, and cytoplasmic CXCR4 breast cancer tissue on metastasis and overall survival in patients with complete-chemotherapy and no-chemotherapy. METHODS: Cohort ambidirectional design was employed with survival analysis that followed the patient's diagnosis until obtaining the outcome, distant metastasis, or death. We analyzed samples in three groups (all-patient, no-chemotherapy, and complete-chemotherapy groups).  Breast cancer cell nuclear and cytoplasm expressions of CXCR4 protein were examined using immunohistochemistry. Amplification of mRNA SDF1a of breast cancer tissue was examined using rtPCR on 131 samples from the same initial paraffin block. RESULTS: In the distant metastasis and Overall Survival (OS) analysis, there was no correlation between cytoplasmic and nuclear CXCR4 in all-patient, no-chemotherapy, and complete-chemotherapy groups. SDF1a was significantly correlated to shorter distant metastasis and poor OS in the all-patient (p=0.004 and p=0.04, respectively) and no-chemotherapy group (p=0.008 and p=0.026, respectively). However, in the complete-chemotherapy group, SDF1a was not correlated to either metastasis (p=0.527) or OS (p=0.993), advanced stage demonstrated a strong association on shorter distant metastatic in no-chemotherapy (p=0.021) and complete-chemotherapy group (p=0.004) and also poor OS in both groups (p=0.006 and p=0.002, respectively). The hormone receptor showed a protective effect on the no-chemotherapy group's OS (p= 0.019). Meanwhile, not undergoing chemotherapy was associated with poor OS in the all-patient group (p= 0.011). CONCLUSION: SDF1a mRNA amplification has a significant correlation with the occurrence of metastasis and OS in all-patient and no-chemotherapy group. Undergoing chemotherapy negates the effect of SDF1a for distant metastasis and OS.

4-Acetylantroquinonol B induced DNA damage response signaling and apoptosis via suppressing CDK2/CDK4 expression in triple negative breast cancer cells.

BACKGROUND: Triple-negative breast cancer (TNBC) has a more aggressive phenotype and poorer prognosis than hormone receptor (HR+) and human epidermal growth factor receptor (HER2 -) subtypes. Inhibition of cyclin-dependent kinase (CDK)4 and CDK6 was successful in patients with advanced metastatic HR+/HER2- breast cancer, but those with TNBC exhibited low or no response to this therapeutic approach. This study investigated the dual therapeutic targeting of CDK2 and CDK4 by using 4-acetyl-antroquinonol B (4-AAQB) against TNBC cells. METHODS: We examined the effects of CDK2, CDK4, and CDK6 inhibition through 4-AAQB treatment on TNBC cell lines and established an orthotropic xenograft mouse model to confirm the in vitro results of inhibiting CDK2, CDK4, and CDK6 by 4-AAQB treatment. RESULTS: High expression and alteration of CDK2 and CDK4 but not CDK6 significantly correlated with poor overall survival of patients with breast cancer. CDK2 and CDK4 were positively correlated with damage in DNA replication and repair pathways. Docking results indicated that 4-AAQB was bound to CDK2 and CDK4 with high affinity. Treatment of TNBC cells with 4-AAQB suppressed the expression of CDK2 and CDK4 in vitro. Additionally, 4-AAQB induced cell cycle arrest, DNA damage, and apoptosis in TNBC cells. In vivo study results confirmed that the anticancer activity of 4-AAQB suppressed tumor growth through the inhibition of CDK2 and CDK4. CONCLUSION: The expression level of CDK2 and CDK4 and DNA damage response (DDR) signaling are prominent in TNBC cell cycle regulation. Thus, 4-AAQB is a potential agent for targeting CDK2/4 and DDR in TNBC cells.

Quality of Life in Palliative Post-mastectomy Reconstruction: Keystone versus Rotational Flap.

Late stage breast cancer presents with malignant wound causing skin infiltration, pain, bleeding, and malodour, which affect quality of life (QoL). Palliative mastectomy aims to eliminate wound symptoms and requires prolonged wound care to improve QoL. This study aimed to prospectively investigate QoL differences in 2 alternative reconstructive methods: keystone flap and rotational flap. METHODS: Twenty-four late stage breast cancer patients with symptoms of cancer wounds were included in this study. They were divided into 2 groups: keystone flap and rotational flap. Each patient's QoL was evaluated using EORTC QLQ-C30 and QLQ-BR23 before and 3 weeks after surgery. RESULTS: Global health post-surgery was significantly improved compared with pre-surgery in all patients (P < 0.001), across both the keystone (P = 0.018) and rotational groups (P = 0.007). Breast symptoms post-surgery were also improved compared with pre-surgery in all patients (P = 0.035). However, when analyzed per group, breast symptoms were only improved significantly in the keystone group (P = 0.013) but not in the rotational group (P = 0.575). When compared between 2 groups, future perspective post-surgery in the keystone group [100 (0-100)] was better than the rotational group [66.7 (0-100)], (P = 0.020). CONCLUSIONS: Reconstructive surgery after mastectomy improves QoL in late stage breast cancer patients. The keystone flap is superior to the rotational flap in improving global health and breast symptoms.

Regional lymph node infiltration and thick lesions are associated with poor prognosis in high-risk resected melanomas: A retrospective cohort study.

BACKGROUND: Acral lentiginous and mucosal melanoma that represent lesions without cumulative sun-induced damages account for 65% of melanomas among Asians but constitute only 5% in Caucasians. The distinct clinical manifestations might influence the clinical course, response to treatment, and outcomes. Factors associated with the prognosis of high-risk resected melanoma in Asians are still rarely reported. METHODS: Clinical, histological determinants of non-distant metastatic melanoma patients who underwent complete resection in 2014-9 were analyzed. RESULTS: Mucosal melanoma, nodular melanoma, and acral lentiginous melanoma accounted for 45.1%, 40.2%, and 14.2% of total melanoma cases (N = 82), respectively. Among cutaneous melanomas, all patients were diagnosed with Breslow's depth more than 4 mm (T4), 51% with ulceration, 95.6% with diameter more than 6 mm, 59% with lympho-vascular invasion, and 74% with regional lymph node infiltration. In mucosal melanomas, 78.3% were diagnosed in advanced stages, 14.5% with regional spread to lymph nodes and 77% with regional infiltration beyond mucosa. Lesions with ulceration were associated with higher risk of distant metastasis (OR 3.003, 95%CI:1.01-9.09). Infiltration into regional lymph node was associated with shorter overall survival (median survivals were 17 vs 23.4 months, Mantel-Cox test P = 0.049). Patients diagnosed at Breslow T4 were also associated with poorer overall survival than T1-3 (median survivals were 23 vs 32 months, Mantel-Cox test P = 0.047). CONCLUSION: The majority of melanoma patients in our population were diagnosed in advanced stages with a higher risk for recurrence and progression into distant metastasis. Regional lymph node involvement and thicker tumor (T4) were associated with poor prognosis.

MicroRNA-223 is Associated with Resistance Towards Platinum-based Chemotherapy and Worse Prognosis in Indonesian Triple-negative Breast Cancer Patients.

PURPOSE: Determining the optimal strategy to implement systemic treatment modalities has been challenging in triple-negative breast cancer (TNBC). We aim to investigate the role of microRNA-223 (miR-223) as prognostic factor and predictor of response toward chemotherapy in TNBC. PATIENTS AND METHODS: We retrospectively analyzed the association of pretreatment miR-223 expression with clinicopathologic characteristics and 36-month overall survival (OS) of 53 all stages TNBC patients. Tumor level of miR-223 was measured using real-time quantitative polymerase chain reaction (expressed in fold change). Cutoff value for miR-223 was determined by using receiver operating curve (ROC). Kaplan-Meier curve was used to perform survival analysis. RESULTS: The optimum cutoff value for miR-223 was 23.435 (AUC: 0.706, 95%CI: 0.565-0.848; p:0.01; sensitivity: 78.6%; specificity: 56%) and was used to categorize mir-223 expression into over- and underexpressed group. Overexpression of miR-223 was associated with increased expression of EGFR (69.7% vs 35%, p: 0.022) and lower 36-month OS (33.3% vs 70%; median OS±SE (months): 25.66±1.58 vs 30.23±1.99; log rank p<0.05). Worse survival is observed in miR-223 overexpressed group receiving platinum-based chemotherapy compared to miR-223 underexpressed group (mean OS (95%CI) months: 24.7 (20.3-29.1) vs 34.3 (31.2-37.4); p<0.01), while no significant difference observed in non-platinum containing regimen. No significant association was observed between miR-223 expression with other clinicopathologic characteristics. CONCLUSION: Overexpression of miR-223 is associated with increased expression of EGFR, worse prognosis, and resistance toward platinum-based chemotherapy in Indonesian TNBC patients.