Clinicopathological Features Of Breast Cancer Research Articles

Clinico-pathological characteristics among South African women with breast cancer receiving anti-retroviral therapy for HIV

PurposeBreast cancer is the most common cancer in women and a leading cause of cancer-related mortality worldwide. South Africa has the largest global burden of HIV infection and the largest anti-retroviral treatment (ART) program. This study aimed to analyse the association of HIV and ART use with breast cancer clinico-pathological characteristics. MethodsStudy participants were females, newly diagnosed from May 2015 through September 2017 with invasive breast cancer at two academic Surgical Breast Units in Johannesburg, South Africa at the Charlotte Maxeke Johannesburg Academic Hospital and Chris Hani Baragwanath Academic Hospital. We compared HIV-positive and HIV negative patients' demographic and clinical-pathological characteristics at the time of breast cancer diagnosis. ResultsOf 1050 patients enrolled, 1016 (96.8%) had known HIV status, with 226 (22.2%) being HIV positive. HIV positive patients were younger (median (IQR) age 45 (40–52) years), than HIV-negative patients (median (IQR) age 57 (46–67)) (p < 0.001). HIV positive patients were more likely to be diagnosed with late stage breast cancer (p = 0.01). However, HIV positive patients receiving ART at the time of breast cancer diagnosis were less likely to present with metastatic disease than those not on ART (p = 0.05). ConclusionHIV-positive patients present with breast cancer at a younger age and later stage disease than HIV-negative patients. Neither the duration of HIV infection nor ART use was associated with clinico-pathological characteristics of breast cancer.

日本人の家族性乳癌におけるBRCA1，BRCA2 遺伝子変異と臨床病理学的特徴の検討

日本人の家族性乳癌におけるBRCA1，BRCA2 遺伝子変異と臨床病理学的特徴の検討

Clinicopathological features of breast cancer in Japanese female patients with Lynch syndrome

Lynch syndrome (LS) is a predominantly inherited syndrome caused by a pathological germline mutation in one of the mismatch repair (MMR) genes. Whether breast cancer (BC) is one of the LS-associated tumors is controversial. The aim of this retrospective cohort study was to evaluate the clinical features of BC in Japanese patients with LS. Of 38 mutation carriers, 4 females with BC were examined in this study. Two of the four patients had multiple BC. Their median age at the diagnosis of BC was 63 (range, 47-84)years. The TNM (6th revision) stages of the six BCs were as follows: stage I, 33% (2/6); stage IIA, 50% (3/6); and stage IIB, 17% (1/6). Histological examination revealed four scirrhous, one papillotubular, and one medullary carcinoma. The positive ratios for estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth receptor 2 (HER2) were 83.3% (5/6), 83.3% (5/6), and 16.7% (1/6), respectively. Two of the three specimens showed MSI-H and one showed MSS. These MSI-H BCs had tumor-infiltrating lymphocytes. Two of the three specimens showed an absence of MLH1 and PMS2 proteins on immunohistochemistry. The cumulative risks for a person with LS to develop BC were 4.35% at the age of 50years, 8.70% at 60years, and 21.5% at 70years. Our study results showed BC in Japanese females with LS to be an MSI-H tumor, which was ER and PgR positive and HER2 negative.

Clinicopathological and prognostic significance of GLUT1 in breast cancer: A meta-analysis.

Background:Previous studies examining the prognostic value of glucose transporter 1 in breast cancer have yielded inconsistent results. We, therefore, performed a meta-analysis to clarify this issue.Methods:The research was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Relevant studies were retrieved from PubMed, Web of Science, EMBASE, and Cochrane library.Results:A total of 7 reports with 1861 patients were finally chosen. GLUT1 overexpression was found to be associated with high histological grade (OR = 3.74, 95% CI = 2.45–5.69, P < .001), negative PR status (OR = 0.33, 95% CI = 0.22–0.49, P < .001), and negative estrogen receptor (ER) status (OR = 0.27, 95% CI = 0.17–0.42, P < .001). However, no significant correlation was seen between GLUT1 levels and presence of lymph node metastasis, tumor size or the status of human epidermal growth factor receptor 2 (HER2). Overexpression of GLUT1 also correlated with a poor overall survival (hazard ratio [HR] = 1.65, 95% confidence interval [CI] = 1.17–2.31, P = .004) and disease-free survival (HR = 2.35, 95% CI = 1.4–3.94, P < .001). No evidence of significant publication bias was found.Conclusion:This meta-analysis indicates that GLUT1 expression is associated with poor prognostic and a series of clinicopathological features in breast cancer. GLUT1 might be a potential biomarker and therapeutic target in breast cancer.

Homeoprotein DLX4 expression is increased in inflammatory breast cancer cases from an urban African-American population.

Protein expression of Distal-less homeobox 4 (DLX4) was analyzed in inflammatory breast cancer (IBC) cases from an African-American (AA) population to determine if a) DLX4 gene over expression exists in this cohort and b) if the overexpression is associated with breast cancer clinicopathological characteristics (ER, PR, HER2, triple-negative). Twenty-nine blocks of formalin-fixed paraffin-embedded (FFPE) tissue from well-characterized human IBC cases were used for immunohistochemical staining (IHC). IHC results were assigned an intensity and percentage score. Percentage scores were assigned as 0, 1, 2, 3, or 4 and intensity scores were assigned 0, 1+, 2+ or 3+. For the analysis of the IHC, a percentage score of 3 or 4 and an intensity score of 2+ or 3+ were categorized as high. Chi-square or Fisher's exact tests were used to compare the high and low groups.In this cohort, 89.7% (26 out of 29) of IBC cases showed high percentages of positive cells staining for the DLX4 protein, while 40.0% (12 out of 30) of normal breast tissue from reduction mammoplasty cases demonstrated DLX4 expression (p < 0.01). In IBC patients, 65.5% of cases showed a high level of staining intensity, compared to 20.0% of normal breast tissues (test, p = 0.001). Intensity to DLX4 was higher in the HER2 negative status (78.3%) than the HER2 positive status (16.7%) (test, p = 0.011).DLX4 expression is higher in the IBC cases in this study of an urban AA population than in normal breast tissue cases. HER2 negative status is positively associated with high intensity of DLX4.

Obesity and Breast Cancer: Association of Serum Adiponectin, Leptin, and Adiponectin–Leptin Ratio as Risk Biomarkers

AbstractIntroduction: Obesity has been associated with the development of breast cancer. The objectives were to study the association of serum adiponectin, serum leptin, and adiponectin–leptin ratio (ALR) in patients with breast cancer and matched controls, and to study their relationship with the various clinicopathological characteristics of breast cancer. Materials and Methods: A prospective, hospital-based case–control study was conducted on 40 patients with a first-confirmed histopathology diagnosis of breast cancer and 40 controls comprising individuals without a history of cancer simultaneously recruited from the health examination clinics during the same study period. Serum adiponectin and leptin concentrations were measured in a single run using commercially available kits (Human ADP/Acrp30 [adiponectin] enzyme-linked immune-sorbent assay [ELISA] kit and Human Leptin ELISA kit, Elabscience Biotechnology Co., Ltd) according to the manufacturer's instructions. Results:: Serum adiponectin levels were reduced significantly in breast cancer patients, in comparison to controls (P = 0.04), while serum leptin levels were increased significantly in breast cancer patients, in comparison to controls (P = 0.03). ALR was significantly lower in breast cancer cases, in comparison to controls (P = 0.05). There was no correlation between receptor status (estrogen receptor, progesterone receptor, Her2/neu), aggressiveness of disease in terms of tumor size, nodal metastases, stage, tumor grade, and serum adiponectin levels, leptin levels, or ALR. Body mass index was negatively correlated with serum adiponectin levels and ALR (r = 0.33, P = 0.03; r = 0.39, P = 0.01, respectively) and positively correlated with serum leptin levels (r = 0.34, P = 0.02). Conclusion: In summary, our results suggest that low serum adiponectin levels, ALR, and high serum leptin levels are associated with breast cancer.

Breast cancer metastasis suppressor gene, breast cancer metastasis suppressor 1, may be associated with clinicopathological features of breast cancer.

We aim to investigate whether the breast cancer metastasis suppressor gene, breast cancer metastasis suppressor 1 (BRMS1), is correlated with clinicopathological features of breast cancer or not. Following a stringent inclusion and exclusion criteria, case-control studies related to the association between BRMS1 and breast cancer were selected from articles retrieved by electronic database searches. All statistical analyses were performed by Stata version 12.0 (Stata Corp, College Station, TX, USA). A total of 12 studies were ultimately included in this meta-analysis. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower compared with normal breast tissues (odds ratio [OR] =0.08, 95% confidence interval [CI] =0.04-0.15, P < 0.001). The BRMS1 protein in metastatic breast cancer tissue was lower than that in nonmetastatic breast cancer tissue (OR = 0.20, 95% CI = 0.13-0.29, P < 0.001), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1, 2 was found to be higher than TNM stages 3, 4 (OR = 4.62, 95% CI = 2.77-7.70, P < 0.001). With respect to breast cancer types, BRMS1 protein in all the three major types of breast cancer was lower than the normal tissues. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. Our meta-analysis results showed that reduced BRMS1 expression level was significantly associated with clinicopathological features of breast cancer, suggesting that loss of expression or reduced levels of BRMS1 might be a strong indicator of the metastatic capacity of breast cancer, with poor prognosis.

Extent of breast cancer type 1 promoter methylation correlates with clinicopathological features in breast cancers.

The current meta-analysis investigated the correlation between breast cancer type 1 (BRCA1) promoter methylation and the clinicopathological features of breast cancer (BC). An electronic literature search was performed to identify and select cohort studies, by employing stringent inclusion and exclusion criteria, for data relevant to promoter methylation of BRCA1 and BC. Statistical analysis of the extracted data was performed using comprehensive meta-analysis 2.0 software (CMA 2.0) (Biostat Inc., Englewood, New Jersey, USA). A total of 125 published studies were retrieved from the literature search, and finally, 18 cohort studies meeting our inclusion criteria were incorporated into our meta-analysis. The 18 studies contained a total of 3213 BC patients. Meta-analysis results revealed that BRCA1 promoter methylation in BC patients with high and moderately differentiated tumors (I-II) was significantly lower than patients with poorly-differentiation tumors (III) (odds ratio [OR] =0.450, 95% confidence interval [95% CI] =0.241-0.838, P = 0.012). BRCA1 promoter methylation in BC patients with lymph node (LN) metastasis was significantly higher than patients without LN metastasis (OR = 2.244, 95% CI = 1.278-3.940, P = 0.005). The results of ethnicity-based subgroup analysis showed a significant difference in histological grade of BC on Asians, LN metastasis of BC in Asians and Caucasians, subtypes of BC in Caucasians, and age at diagnosis of BC patients in Caucasians (all P < 0.05). Our meta-analysis revealed that BRCA1 promoter methylation status is linked to tumor grade and LN metastasis of BC.

Intratumoral heterogeneity on dedicated breast positron emission tomography predicts malignancy grade of breast cancer.

Dedicated breast positron emission tomography (DbPET) provides detailed high-resolution images and can detect intratumoral heterogeneity using 18F-fluorodeoxyglucose (FDG). We aimed to evaluate the correlation between FDG uptake on DbPET and the clinicopathological features of breast cancer, particularly those with an intratumoral heterogeneous distribution of FDG on DbPET. We evaluated 195 consecutive patients with invasive breast cancer who underwent preoperative whole-body PET (WBPET) and DbPET concurrently between January 2016 and March 2017. The relationships between clinicopathological factors and the maximum standard uptake values (SUVmax) of DbPET and WBPET, including clinical stage, nuclear grade, Ki67 proliferation index, estrogen receptor (ER) and human epidermal growth factor receptor type 2 (HER2) statuses, and the intratumoral heterogeneous distribution of FDG on DbPET, were evaluated. The SUVmax of DbPET was significantly correlated with clinical T stage, N stage, nuclear grade, and Ki67 proliferation index (all p < 0.001) as well as the ER (p = 0.006) and HER2 (p = 0.040) statuses. Intratumoral heterogeneous distribution of FDG on DbPET was significantly related with high nuclear grade (p = 0.016) and high Ki67 proliferation index (p = 0.015) but not with clinical T stage, N stage, and ER and HER2 statuses. The SUVmax of DbPET correlates with clinicopathological factors and also WBPET does. In addition, intratumoral heterogeneity on DbPET provides predictive value for malignancy grade and could inform therapeutic decisions.

Effect of glucocorticoid use on survival in patients with stage I-III breast cancer.

Glucocorticoids (GCs) are commonly used in breast cancer patients to ameliorate emesis induced by chemotherapy. Some preclinical studies have suggested that systemic GCs might promote survival of estrogen receptor (ER)-negative breast cancer cells. This study aims to clarify their clinical effect on patient survival. A total of 18,596 women with newly diagnosed stage I-III breast cancer in 2002-2006 were identified from the Taiwan Cancer Database and drug treatment was examined from the Taiwan National Health Insurance Claims Database. Of these, 3989 who did not receive adjuvant chemotherapy (non-chemotherapy cohort) and 3237 patients who received six cycles of adjuvant anthracycline-based chemotherapy (anthracycline cohort) were included. The impact of GC use on survival was analyzed separately in these two cohorts using Cox proportional hazards models. In the non-chemotherapy cohort, GC use was associated with aggressive clinicopathological features of breast cancer. High-dose GC was associated with shorter overall survival in univariate analysis but not in multivariate analysis. In the anthracycline cohort, multivariate analysis showed that GC use at each dose level was significantly associated with longer breast cancer-specific survival (HR 0.65, 0.70, and 0.70 for low-dose, median-dose, and high-dose GC, respectively) and overall survival (HR 0.72, 0.76, and 0.73, respectively) when compared with those receiving no GC. The associations were significant in both ER-positive and ER-negative subgroups for breast cancer-specific survival, and in ER-negative subgroup for overall survival. Concomitant use of GC improved survival in patients receiving adjuvant anthracycline-based chemotherapy for stage I-III breast cancer.

Association of FGFR2 and PI3KCA genetic variants with the risk of breast cancer in a Chinese population.

PurposeGenome-wide association studies have found plenty of single nucleotide polymorphisms (SNPs) which are associated with breast cancer risk. SNPs in FGFR2 are mostly identified. However, the association between PI3KCA SNP and breast cancer risk remains largely unknown. The aim of this study was to investigate the significance of FGFR2 and PI3KCA genetic variants in breast cancer and their association with prognosis.MethodsWe performed genotyping of 328 breast cancer patients and 389 healthy controls. Then, we evaluated the associations of FGFR2 rs1219648 and PI3KCA rs6443624 with the susceptibility and clinicopathological features of breast cancer. Kaplan-Meier curve with log-rank test was performed to determine the prognostic values of FGFR2 rs1219648 and PI3KCA rs6443624.ResultsThe results indicated that genotype frequencies of rs1219648 and rs6443624 were significantly different between breast cancer patients and healthy controls. Furthermore, PI3KCA rs6443624 A carriers and FGFR2 rs1219648 G carriers more frequently had advanced stages and shorter survival times.ConclusionThe SNPs of FGFR2 rs1219648 and PI3KCA rs6443624 may contribute to the identification of breast cancer patients at risk of more aggressive disease and may be potential prognostic factors in breast cancer in a Chinese population.

Significant association between ERCC2 and MTHR polymorphisms and breast cancer susceptibility in Moroccan population: genotype and haplotype analysis in a case-control study

BackgroundGenetic determinants of breast cancer (BC) remained largely unknown in the majority of Moroccan patients. The purpose of this study was to explore the association of ERCC2 and MTHFR polymorphisms with genetic susceptibility to breast cancer in Moroccan population.MethodsWe genotyped ERCC2 polymorphisms (rs1799793 (G934A) and rs13181 (A2251C)) and MTHFR polymorphisms (rs1801133 (C677T) and rs1801131 (A1298C)) using TaqMan SNP Genotyping Assays. Genotypes were compared in 151 BC cases and 156 population-matched controls. Allelic, genotypic and haplotype associations with the risk and clinicopathological features of BC were assessed using logistic regression analyses.ResultsERCC2-rs1799793-AA genotype was associated with high risk of BC compared to wild type genotype (recessive model: OR: 2.90, 95% CI: 1.34–6.26, p = 0.0069) even after Bonferroni correction (p < 0,0125). MTHFR rs1801133-TT genotype was associated with increased risk of BC (recessive model, OR: 2.49, 95% CI: 1.17–5.29, p = 0.017) but the association turned insignificant after Bonferroni correction. For the rest of SNPs, no statistical associations to BC risk were detected.Significant association with clinical features was detected for MTHFR-rs1801133-TC genotype with early age at diagnosis and familial BC. Following Bonferroni correction, only association with familial BC remained significant. MTHFR-rs1801131-CC genotype was associated with sporadic BC. ERCC2-rs1799793-AA genotype correlated with ER+ and PR+ breast cancer. ERCC2-rs13181-CA genotype was significantly associated large tumors (T ≥ 3) in BC patients. None of these associations passed Bonferroni correction.Haplotype analysis showed that ERCC2 A-C haplotype was significantly associated with increased BC risk (OR: 3.71, 95% CI: 1.7–8.12, p = 0.0002 and p = 0.0008 before and after Bonferroni correction, respectively) and positive expression of ER and PR in BC patients. ERCC2 G-C haplotype was correlated with PR negative and larger tumor (T4). We did not find any MTHFR haplotypes associated with BC susceptibility. However, the less common haplotype MTHFR T-C was more frequent in young patients and in familial breast cancer, while MTHFR C-C haplotype was associated with sporadic BC form.ConclusionsOur findings are a first observation of association between ERCC2 SNPs and breast cancer in Moroccan population. The results suggested that ERCC2 and MTHFR polymorphisms may be reliable for assessing risk and prognosis of BC in Moroccan population.

Significance of EGFR mRNA Expression in Luminal and Triple Negative Breast Tumors

Background: The epidermal growth factor receptor (EGFR) has critical roles in signal transduction pathways, leading to cell growth and differentiation. EGFR expression levels vary among different breast tumor subtypes and ethnic groups. On the other hand, the relationship between EGFR expression at the mRNA level with clinicopathological characteristics in breast cancer has rarely been reported. Objectives: The present study focuses on the assessment of EGFR mRNA expression in breast tumors and the association of its expression with various clinicopathological features in Iranian patients with breast cancer. Methods: In this cross sectional study, the expression of EGFR was assessed by real time PCR technique in tumors of 52 Iranian women (27 luminal and 25 triple negative tumors) with primary breast cancer and 6 normal breast tissues. Results: The results of this study showed that EGFR mRNA was overexpressed only in triple negative tumors, and there is a high frequency of EGFR underexpression in luminal breast tumors, unlike triple negative tumors. We demonstrated that there is a significant positive correlation (r = 0.662) between EGFR expression and the size of luminal tumors. In the current study, the increased expression of EGFR is significantly associated with estrogen receptor (ER) negative, progesterone receptor (PR) negative, and grade III in breast tumors. Conclusions: These findings suggest that the majority of patients with triple negative tumors are likely eligible to receive the anti-EGFR therapies. Also, it seems that EGFR expression probably has an association with tumor size in luminal subtype of breast tumors.

Tumor necrosis factor: An inflammatory microenvironment marker in primary breast cancer patients

&lt;strong&gt;Aim: &lt;/strong&gt;The present study was planned to analyze plasma levels of tumor necrosis factor (TNF) in invasive ductal primary breast cancer (BC) patients in a South Indian population. TNF alpha (TNF α) and TNF beta (TNF β) are produced during inflammation as proinflammatory cytokine markers. The plasma levels of TNF α and TNF β (lymphotoxin α) were correlated with clinicopathological features of BC. &lt;strong&gt;Materials and Methods: &lt;/strong&gt;Blood samples were collected from patients before treatment. We analyzed plasma levels of TNF α, and TNF β in 70 female BC cases and 35 age-matched healthy controls using Millipore magnetic bead kits. &lt;strong&gt;Results: &lt;/strong&gt;Plasma TNF α levels in BC cases were significantly elevated (median 10.1 pg/ml) when compared to the control groups. Plasma values of TNF α and TNF β both were significantly elevated in BC patients with hormone receptor negative cases. Plasma TNF α level was elevated in lymph node metastasis and triple negative BC. Plasma values of TNF α inversely correlated with estrogen receptor and progesterone receptor positivity. &lt;strong&gt;Conclusion: &lt;/strong&gt;The plasma levels of TNF α were more significantly overexpressed than TNF β in BC patients. Further, the patients with aggressive cancer had higher levels of inflammation markers. The present study shows that TNF levels were elevated in hormone receptor negative and triple-negative cases.&lt;p&gt; &lt;/p&gt;

Erythropoietin-producing hepatocellular A6 overexpression is a novel biomarker of poor prognosis in patients with breast cancer.

Erythropoietin-producing hepatocellular A6 (EphA6) is a member of the Eph receptor tyrosine kinase family, which has been implicated in tumorigenesis. However, little is known about the expression and function of EphA6 in breast cancer. The aim of the present study was to investigate the expression of EphA6 and the possible association between EphA6 and clinicopathological characteristics in breast cancer. In the present study, EphA6 mRNA expression was measured in 26 paired breast cancer tissues and adjacent non-cancerous tissues by reverse transcription-quantitative polymerase chain reaction. Additionally, the protein expression of EphA6 in breast cancer tissues from 116 patients was examined by immunohistochemistry, and the prognostic value for patients with breast cancer was evaluated. The results of the present study indicated that EphA6 mRNA and protein expression in breast cancer was significantly higher than that in adjacent non-cancerous tissues (P<0.001). EphA6 overexpression was significantly associated with a high histological grade (P<0.001), overexpression of human epidermal growth factor 2 (HER-2; P=0.0106), low estrogen receptor expression (P=0.0247) and low progesterone receptor expression (P=0.0015). Furthermore, the increased expression of EphA6 was demonstrated to be associated with breast cancer subtypes (P=0.0164). Kaplan-Meier curves demonstrated that high EphA6 expression was associated with lower overall survival rates in patients with breast cancer (P=0.015). Univariate and multivariate analysis revealed that high EphA6 expression, Tumor-Node-Metastasis classification and subtype were independent prognostic factors for patients with breast cancer (all P<0.05). In conclusion, EphA6 may serve an important role in breast carcinogenesis and may pose as a novel prognostic indicator and therapeutic target for breast cancer, particularly in patients with steroid receptor negative expression and HER-2 overexpression.

Hypoxia-Induced TPM2 Methylation is Associated with Chemoresistance and Poor Prognosis in Breast Cancer

Background/Aims: Tropomyosin-2 (TPM2) plays important roles in functions of the cytoskeleton, such as cytokinesis, vesicle transport, cell proliferation, migration and apoptosis,and these functions imply that TPM2 also plays a role in cancer development. Indeed, it has been shown that TPM2 plays a critical role in some cancers. However, the role of TPM2 in breast cancer is still poorly characterized. Thus, we explored the role of TPM2 in breast cancer. Methods: We analysed TPM2 expression and its correlation with the clinicopathological features in breast cancer. Then, we examined the influence of hypoxia on TPM2 expression and methylation status using bisulfite sequencing PCR. Furthermore, we performed TPM2-mediated migration and invasion assays in the context of hypoxia and examined changes in matrix metalloproteinase-2 (MMP2) expression. Finally, we detected the influence of TPM2 on survival and chemotherapy drug sensitivity. Results: We found that TPM2 expression is down-regulated in breast cancer cells compared to that in normal breast cells. The data from TCGA supported these results. Promoter methylation of TPM2, which could be induced by hypoxia, was responsible for its low expression. Hypoxia might regulate cell invasiveness partly by TPM2 down-regulation-mediated changes of MMP2 expression. Importantly, low TPM2 expression was correlated with lymph node metastasis (P=0.031), tumour node metastasis stage (P=0.01), histological grade (P=0.037), and shorter overall survival (P=0.028). Univariate and multivariate analyses indicated that TPM2 was an independent predictor in breast cancer patients. Paclitaxel chemotherapy did not benefit patients with low TPM2 expression (P<0.0001). TPM2 knockdown significantly reduced cell sensitivity to paclitaxel. Conclusion: TPM2 is a potential novel tumour suppressor gene in breast cancer. TPM2 is associated with poor survival and chemoresistance to paclitaxel in breast cancer, and TPM2 may represent a promising therapeutic gene target for breast cancer patients with chemoresistance.

Paip1 affects breast cancer cell growth and represents a novel prognostic biomarker

Polyadenylate-binding protein-interacting protein 1 (Paip1) regulates translational initiation. Increasing evidence suggests that Paip1 plays important roles in cancer development and progression. This study explored the role of Paip1 in breast cancer progression and evaluated its prognostic value. The cellular location of Paip1 protein was determined using immunofluorescence. Then, Paip1 protein expression was evaluated by immunohistochemical staining in 119 breast cancers and 40 normal breast tissues. The correlation between Paip1 expression and the clinicopathologic features of breast cancer was evaluated using the χ2 test, and differences in survival curves were analyzed using log-rank tests. The role of Paip1 in breast cancer proliferation and cell cycle progression was identified by siRNA transfection. Paip1 was expressed mainly in the cytoplasm of cancer cells and tissues. Expression was observed in 60.5% of the breast cancers (72/119), which was significantly higher than in normal breast tissues (17.5%; 7/40). High expression of Paip1 protein was associated with high histologic grade, late clinical stage, and a low survival rate. Multivariate analysis indicated that Paip1 was an independent prognostic factor. Additionally, Paip1 depletion by RNAi significantly decreased cell proliferation and induced cell cycle arrest. In conclusion, our study demonstrated that Paip1 promotes the growth of breast cancers and could be a prognostic biomarker and therapeutic target.

The association between differentially expressed micro RNAs in breast cancer cell lines and the micro RNA‑205 gene polymorphism in breast cancer tissue

Micro (mi)RNAs are an endogenous non-coding small RNA comprised of 19–26 nucleotides. miRNAs regulate gene expression through the recognition of its ‘seed sequence’ and interactions with 3′-untranslated region of target miRNAs. Previous studies identified that miRNAs are associated with the onset and development of breast cancer and that a number of mutations in the coding DNA sequence of miRNAs affect its expression. Therefore, the present study aimed to screen differentially expressed miRNAs using miRNA expression profile chips to analyze the expression of miRNA (miR)-205 in 12 breast cell lines of different metastatic performance and benign proliferative variation as well as breast cancer via in-situ hybridization, and screen out single-nucleotide polymorphisms (SNPs) in the miR-205 coding gene region. In addition, the association between SNP and the clinicopathological features of breast lesions was investigated. The results of the present study demonstrated that the expression of miR-205 was decreased in breast cancer cells and tissues compared with benign lesions. SNPs in the miR-205 coding gene region were identified in tumor cell lines and as increasing lengths of the AGC repetitive sequence were lost, miR-205 expression increased. An association was identified between a number of SNPs in the miR-205 coding gene region and breast cancer, as well as between SNPs in miR-205 coding gene region and the clinicopathological features of breast cancer.

Survival and time to initiation of adjuvant chemotherapy among breast cancer patients: a systematic review and meta-analysis.

The relationship between survival and time to the start of adjuvant chemotherapy (AC) among breast cancer patients is unclear. In order to illustrate the effect of delaying the initiation of AC on survival we have undertaken a systematic review and meta-analysis.We identified 12 available studies in the meta-analysis including 15 independent analytical groups. This meta-analysis showed that a 4-week delay before AC was associated with a significantly worse overall survival (OS)(HR=1.13; 95% confidence interval [CI], 1.08–1.19) and disease free survival (DFS)(HR=1.14; 95%CI, 1.05–1.24). Two studies categorized patients into hormone receptor-positive, ERBB2-positive, and triple-negative breast cancer (TNBC) patients according to the clinicopathological features of breast cancer. The HRs for OS between waiting time (WT) ≤30 days and 31–60 days in the subgroups were extracted and analyzed. The analysis demonstrated that a WT of 31–60 days was related to worse OS among patients with TNBC (HR, 1.26; 95% CI, 1.08–1.48), but had no significant effect on OS among those with hormone receptor-positive (HR, 1.02; 95% CI, 0.89–1.15) or ERBB2-postive (HR, 0.95; 95%CI, 0.79–1.14) tumors.In this meta-analysis of the eligible literatures reviewing the time to AC, a longer waiting time to adjuvant chemotherapy may lead to worse survival in breast cancer patients, especially in TNBC patients.

563P - Descriptive analysis of clinicopathological characteristics of breast cancer in Sanglah General Hospital, Bali

563P - Descriptive analysis of clinicopathological characteristics of breast cancer in Sanglah General Hospital, Bali