Prognostic Factor In Breast Cancer Research Articles

Immunohistochemical Evaluation of COL11A1 and FGD3 Expression in Invasive Breast Cancer

Background: Collagen type XI, alpha 1 (COL11A1) is a minor component of extracellular matrix and its overexpression is associated with tumoral progression and poorer outcome in several human cancers; data on breast cancer are promising but scarce. FGD3 expression has been shown to be a strong independent prognostic factor in breast cancer. The aim of our study was to investigate whether COL11A1 expression correlates with other classic pathologic prognostic factors including FGD3 expression, as well as with clinical outcome, to evaluate its potential use as prognostic factor in breast cancer patients. Methods: We evaluated by immunohistochemistry COL11A1 expression and we studied the relationship between this protein expression and traditional breast cancer prognostic factors, FGD3 expression, as well as with patients’ outcome. Results: We found that higher stromal COL11A1 expression was associated with higher tumour grade (G3) (p = 0.001), higher Ki67 proliferation index (p = 0.006), more advanced AJCC stage (p = 0.031) and lower FGD3 expression (p = 0.039). In a case-control analysis, we observed that patients with high-COL11A1 had a higher risk of recurrence (OR = 2.0) and of dying of the disease (OR = 2.0). Patients with high-COL11A1-expressing tumours had shorter disease-free survival and overall survival (difference not significant). There was a linear positive correlation between COL11A1 expression on epithelial tumoral cells and surrounding stromal cells (r = 0.247, p = 0.04). Conclusion: Our findings suggest that COL11A1 may represent a marker of aggressiveness in invasive breast cancer and that its detection warrants further study on larger series to evaluate its possible use in clinical practice.

Prognostic influences of B-cell lymphoma 2-positive expression on late recurrence in breast cancer.

B-cell lymphoma 2 (BCL2) has an antiapoptotic role, however, has resulted in it being a powerful favorable prognostic factor in breast cancer. Several studies revealed BCL2 is strongly associated with a lower rate of early recurrence after initial treatment in breast cancer patients, but study of a prolonged effect after 5 years is lacking. We investigated BCL2 as a prognostic factor in breast cancer in comparison to early and late recurrence. We retrieved data from 2,198 patients with primary breast cancer who underwent surgical treatment and adjuvant treatment at the breast cancer center between 2005 and 2015. Each molecular subtype was classified, and Ki-67 and BCL2 were also assessed by immunohistochemistry. BCL2 and the association between molecular subtypes were assessed in early and late recurrences, respectively. Five-year postrecurrence survival and BCL2 were also assessed. The BCL2-positive group was associated with favorable clinicopathologic characteristics. The time to recurrence was significantly longer in the BCL2-positive group (P = 0.035). Late recurrence after 5 years was higher in the BCL2-positive group (P = 0.029). In multivariate survival analysis, tumor size and BCL2-positive expression were the only independent prognostic factors for late recurrence (P = 0.004). In the patients with recurrence, 5-year postrecurrence survival was significantly higher in the BCL2-positive group (P < 0.001). Our result showed that prognosis was better in BCL2-positive patients compared to BCL2-negative patients at late recurrence. We suggested that BCL2 expression could be used as a marker to help determine additional adjuvant therapy or extended hormone therapy in hormone-dependent breast cancer.

Can TILs be associated with prognostic factors and survival rates in breast cancer? A retrospective analysis

Introduction: The relationship between the tumor inflammatory infiltrate, also known as tumor-infiltrating lymphocytes (TILs), and invasive breast carcinomas has been extensively studied in recent years to verify its association with prognosis and response to treatment. The goal of this study was to associate the presence of TILs with patient’s survival time. Methods: We studied prognostic clinicopathological characteristics already established in the literature and their impact on overall five-year survival time of patients with invasive breast cancer treated at Hospital Santa Casa in Belo Horizonte, Minas Gerais, Brazil, in 2011 (n=290). This was an observational and retrospective study. Results: The presence of TILs was associated with tumors of no special type (p=0.018) and with younger age of the patients (p=0.042). Smaller tumor size (HR: 19.24; 95%CI 4.30–86.15; p&lt;0.001), absence of metastasis to the axillary lymph nodes (HR: 2.80; 95%CI 1.02–7.70; p=0.002), positivity for progesterone receptor (HR: 0.39; 95%CI 0.17–0.87; p=0.022), and presence of TILs (HR: 0.23; 95%CI 0.08–0.65; p=0.005) were associated with longer survival times. Conclusions: This study suggests that the presence of TILs, along with other clinicopathological characteristics, is a prognostic factor in breast cancer.

Validation of bioelectrical impedance analysis in the evaluation of body composition in patients with breast cancer.

The evaluation of body composition is an essential parameter for preventing obesity and sarcopenic obesity, which are prognostic factors in breast cancer. This study aims to validate the bioelectrical impedance analysis (BIA) of women who are breast cancer survivors by using the dual-energy x-ray absorptiometry (DXA) measurement method. This validation study included 104 women without metastasis between 32 and 72 years old (mean 47.03 ± 8.59) whose treatment was completed 6 months prior. Body composition analysis was performed sequentially using both measurements and when participants were hungry. Meaningful differences were found in fat-free mass (FFM) (BIA: 46.57 ± 5.54 kg; DXA: 41.06 ± 5.11 kg), body fat percentage (%BF) (BIA: 34.28% ± 6.24%; DXA: 43.91% ± 5.58%), body fat mass (FM) (BIA: 25.37 ± 8.84 kg; DXA: 31.24 ± 9.09 kg), and lean soft tissue mass (LSTM) (BIA: 4.42 ± 5.66 kg; DXA: 38.75 ± 4.98 kg) (P < 0.001). Powerful associations for body FM and strong associations for other parameters were seen. A constant and/or proportional error was found between the two devices within the direction of strong and solid components. Compared with DXA, the BIA measurement gives a lower estimate of %BF and FM and a higher estimate of LSTM and FFM. By the mathematical relationship between the two measurement methods, it seems possible to adapt the body composition parameters obtained from BIA of patients with breast cancer to DXA results. In the future, there will be a need to evaluate these two devices with more extensive studies.

Systemic Inflammatory Response as a Prognostic Factor in Breast Cancer. Part I. Tumor-Promoting Inflammation. Serum Inflammatory Markers

Chronic inflammation caused by exposure to external or internal factors increases the risk of developing malignancies and promotes tumor progression due to the influence on the key elements of carcinogenic mechanisms. At the system level signs of a chronic inflammation are manifested by an increase of inflammatory mediators and acute phase proteins levels in the blood, a change in the ratio of circulating leukocyte populations, and disturbances in the hemostasis system. This review is devoted to serum and hematological parameters of the systemic inflammatory response (SIR) in breast cancer (BC). The first part of the review outlines general concept about the role of inflammatory factors in the development of malignant tumors. It provides information on the most well studied serum inflammatory markers in breast cancer: cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-), as well as C-reactive protein (CRP). The main properties of these polypeptides, which link them with tumor-promoting inflammation, are considered. An analysis of the data on the clinical significance of the serum level of cytokines and CRP in breast cancer accumulated to date is presented. Correlations of the elevated levels of the serum inflammatory markers with clinical and morphological characteristics of the disease, tumor response to chemotherapy, overall and relapse-free survival of patients indicate the feasibility of in-depth investigation of the issue for the purpose of the practical application of the systemic inflammatory markers as predictive and prognostic indicators in BC.

Clinical Significance of Ultrasound Elastography and Fibrotic Focus and Their Association in Breast Cancer.

(1) Background: Ultrasound (US) elastography is an imaging technology that reveals tissue stiffness. This study aimed to investigate whether fibrotic focus (FF) affects elastographic findings in breast cancer, and to evaluate the clinical significance of US elastography and FF in breast cancer. (2) Methods: In this study, 151 patients with breast cancer who underwent surgery were included. Strain elastography was performed and an elasticity scoring system was used to assess the findings. The elasticity scores were classified as negative, equivocal, or positive. FF was evaluated in the surgical specimens. Medical records were reviewed for all patients. (3) Results: Elastographic findings were equivocal in 30 patients (19.9%) and positive in 121 patients (80.1%). FF was present in 68 patients (46.9%). There was no correlation between elastographic findings and FF. Older age, larger tumor size, lymph node metastasis, and higher tumor stage were associated with positive elastographic results. FF showed a positive correlation with age, postmenopausal status, tumor size, lymphovascular invasion, lymph node metastasis, tumor stage, and intratumoral and peritumoral inflammation. (4) Conclusions: Our study showed that positive elastographic results and FF were associated with poor prognostic factors for breast cancer. FF did not affect the elastographic findings of this study.

The Value of Semiquantitative Parameters Derived from 18F-FDG PET/CT for Predicting Response to Neoadjuvant Chemotherapy in a Cohort of Patients with Different Molecular Subtypes of Breast Cancer

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is a strong prognostic factor in breast cancer (BC). The aim of this study was to investigate whether semiquantitative parameters derived from baseline [18F]Fluorodeoxyglucose ([18F]FDG) positron emission computed tomography/computed tomography (PET/CT) could predict pCR after NAC and survival outcomes in patients affected by different molecular subtypes of BC. We retrospectively retrieved patients from the databases of two Italian hospitals (Centre A: University Hospital of Ferrara; Centre B: University of Padua) meeting the following inclusion criteria: (1) diagnosis of BC; (2) history of NAC; (3) baseline [18F]FDG PET/CT performed before the first cycle of NAC; (4) available follow-up data (response after NAC and survival information). For each [18F]FDG PET/CT scan, semiquantitative parameters (SUVmax, SUVmean, MTV and TLG) related to the primary tumor (B), to the reference lesion for both axillary (N) and distant lymph node (DN), and to the whole-body burden of disease (WB) were evaluated. Patients enrolled were 133: 34 from centre A and 99 from centre B. Patients' molecular subtypes were: 9 luminal A, 49 luminal B, 33 luminal B + HER-2, 10 HER-2 enriched, and 32 triple negative (TNBC). Luminal A and HER-2 enriched BC patients were excluded from the analysis due to the small sample size. pCR after NAC was achieved in 47 patients (41.2%). [18F]FDG PET/CT detected the primary tumor in 98.3% of patients and lymph node metastases were more frequently detected in Luminal B subgroup. Among Luminal B patients, median SUVmean_B values were significantly higher (p = 0.027) in responders (7.06 ± 5.9) vs. non-responders (4.4 ± 2.1) to NAC. Luminal B + HER-2 non-responders showed a statistically significantly higher median MTV_B (7.3 ± 4.2 cm3 vs. 3.5 ± 2.5 cm3; p = 0.003) and TLG_B (36.5 ± 24.9 vs. 18.9 ± 17.7; p = 0.025) than responders at baseline [18F]FDG PET/CT. None of the semiquantitative parameters predicted pCR after NAC in TNBC patients. However, among TNBC patients who achieved pCR after NAC, 4 volumetric parameters (MTV_B, TLG_B, MTV_WB and TLG_WB) were significantly higher in patients dead at follow-up. If confirmed in further studies, these results could open up a widespread use of [18F]FDG PET/CT as a baseline predictor of response to NAC in luminal B and luminal B + HER-2 patients and as a prognostic tool in TNBC.

Automated classification of breast cancer histologic grade using multiphoton microscopy and generative adversarial networks

Histological grade is one of the most powerful prognostic factors for breast cancer and impacts treatment decisions. However, a label-free and automated classification system for histological grading of breast tumors has not yet been developed. In this study, we employed label-free multiphoton microscopy (MPM) to acquire subcellular-resolution images of unstained breast cancer tissues. Subsequently, a deep-learning algorithm based on the generative adversarial network (GAN) was introduced to learn a representation using only MPM images without the histological grade information. Furthermore, to obtain abundant image information and determine the detailed differences between MPM images of different grades, a multiple-feature discriminator network based on the GAN was leveraged to learn the multi-scale spatial features of MPM images through unlabeled data. The experimental results showed that the classification accuracies for tumors of grades 1, 2, and 3 were 92.4%, 88.6%, and 89.0%, respectively. Our results suggest that the fusion of multiphoton microscopy and the GAN-based deep learning algorithm can be used as a fast and powerful clinical tool for the computer-aided intelligent pathological diagnosis of breast cancer.

Glucose metabolism and lncRNAs in breast cancer: Sworn friend.

Glucose metabolism disorder is a common feature in cancer. Cancer cells generate much energy through anaerobic glycolysis, which promote the development of tumors. However, long non-coding RNA may play an important role in this process. Our aim is to explore a prognostic risk model based on the glucose metabolism-related lncRNAs which provides clues that lncRNAs predict a clinical outcome through glucose metabolism in breast cancer. 1222 RNA-seq were extracted from the TCGA database, and 74 glucose metabolism-related genes were loaded from the GSEA website. Then, 7 glucose metabolism-related lncRNAs risk score model was developed by univariate, Lasso, and multivariate regression analysis. The lncRNA risk model showed that high-risk patients predict a poor clinical outcome with high reliability (P=2.838×10-6). Univariate and multivariate independent prognostic analysis and ROC curve analysis proved that the risk score was an independent prognostic factor in breast cancer with an AUC value of 0.652. Finally, Gene set enrichment analysis showed that cell cycle-related pathways were significantly enriched in a high-risk group. Our results showed that glucose metabolism-related lncRNAs can affect breast cancer progression. 7 glucose metabolism-related lncRNAs prognostic signature was established to evaluate the OS of patients with breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors and expressed highly in the high-risk group. A Nomogram was made based on this signature to judge patients' living conditions and prognosis. 7 glucose metabolism-related lncRNAs risk score model had a high prognostic value in breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors. AP001505.1 expression was increased in most triple-negative breast cancer cells treated with high glucose, which may also take part in breast cancer progression and potential therapeutic targets.

Time to surgery and survival in breast cancer

BackgroundThis study aimed to investigate the effect of the time from diagnosis to breast cancer surgery on breast cancer patients’ prognosis.MethodsOf the 1900 patients diagnosed with invasive (stage 1–3) breast cancer who underwent surgery in KUH between 2012 and 2019, 279 patients were enrolled in this study. All patients, including those who received neoadjuvant chemotherapy, were classified as Model 1 subjects, and those who received immediate surgical treatment were classified as Model 2 subjects. We conducted a Cox regression analysis to identify prognostic factors of breast cancer associated with the time from diagnosis to surgery.ResultsThe univariate results indicated a sharp drop in both groups’ survival rates when the time to surgery was delayed for more than 8 weeks (Model 1 p = 0.000; Model 2 p = 0.001). In the multivariate analysis, the hazard ratio (HR) of Model 1increased (HR = 6.84, 95% CI 1.06–44.25) in response to a delay in surgery of more than 8 weeks. Smoking and the American Joint Committee on Cancer (AJCC) staging system had a negative effect on breast cancer prognosis, while hormone therapy had a positive effect.ConclusionFor all patients, a delay in breast cancer surgery of more than 8 weeks was inversely associated with survival.

Development and validation of novel risk prediction models of breast cancer based on stanniocalcin-1 level.

The function of stanniocalcin-1 (STC-1) in the oncogenesis and progression of tumors has been extensively studied. The purpose of this study was to investigate the relationship between secreted STC-1 and prognosis in patients with breast cancer (BC) and to determine whether STC-1 could be a key prognostic factor in BC. The STC-1 level was measured by ELISA and clinical data from 1210 female patients with BC were used to develop and validate nomograms. We then verified the models through the plotting of ROC curves and calibration curves, calculating the C-index, and performing decision curve analyses (DCA). The level of STC-1 in the peripheral plasma was significantly correlated with the T stage, N stage, clinical stage, grade, hormone receptors, HER-2 status, and tumor subtype. Cox regression analyses revealed that estrogen receptor(ER) status, N stage, and STC-1 level were risk factors for overall survival (OS), whereas T stage, N stage, and STC-1 level were independent prognostic factors for distant disease-free survival (DDFS) and disease-free survival (DFS). Both the ROC curve and the C-index confirmed the high resolution of these models, while the DCA identified the feasibility of their practical application. In addition, the calibration curves indicated good consistency between the predicted and actual survival rates. Nomograms were created based on STC-1 levels for 3-, 5-, and 7-year OS, DDFS, and DFS of patients with BC respectively. As a key prognostic factor for BC, peripheral blood STC-1 level can be used clinically as a liquid biopsy indicator.

Reporting of Surgically Removed Lymph Nodes for Breast Tumors: Recommendations From the International Collaboration on Cancer Reporting.

The International Collaboration on Cancer Reporting (ICCR), supported by major pathology and cancer organizations, aims at the standardization of evidence-based pathology reporting of different types of cancers, with the inclusion of all parameters deemed to be relevant for best patient care and future data collection. Lymph node metastasis is one of the most important prognostic factors in breast cancer. To produce a histopathology reporting guide by a panel of recognized experts from the fields of pathology and surgery with elements deemed to be core (required) and noncore (recommended) to report when assessing regional lymph nodes of patients with breast cancer. Published literature, previous guidelines/recommendations, and current cancer staging principles were the basis of the data set drafted by the expert panel. This was discussed in a series of teleconferences and email communications. The draft data set was then made available for public consultation through the ICCR Web site. After this consultation and ICCR ratification, the data set was finalized. The ICCR has published a data set for the reporting of surgically removed lymph nodes (including sentinel lymph node biopsy, axillary lymph node dissection, targeted axillary surgery, and lymph node sampling specimens) for breast tumors. This is part of a series of 4 ICCR breast cancer-related data sets. It includes 10 core elements along with 2 noncore elements. This should allow for synoptic reporting, which is more precise, uniform, and complete than nonsynoptic reporting, and leads to improved patient outcomes.

A novel twelve-gene signature to predict neoadjuvant chemotherapy response and prognosis in breast cancer.

Accurate evaluation of the response to neoadjuvant chemotherapy (NAC) provides important information about systemic therapies for breast cancer, which implies pharmacologicalresponse, prognosis, and guide further therapy. Gene profiles overcome the shortcomings of the relatively limited detection indicators of the classical pathological evaluation criteria and the subjectivity of observation, but are complicated and expensive. Therefore, it is essential to develop a more accurate, repeatable, and economical evaluation approach for neoadjuvant chemotherapy responses. We analyzed the transcriptional profiles of chemo-resistant breast cancer cell lines and tumors of chemo-resistant breast cancer patients in the GSE25066 dataset. We preliminarily screened out common significantly differentially expressed genes and constructed a NAC response risk model using LASSO regression and univariate and multivariate analyses. The differences in bioinformatic features of tumor cells, immune characteristics, and prognosis were compared between high and low-risk group. The potential drugs that could reverse chemotherapy resistance in breast cancer were screened by the CMap database. Thirty-six genes were commonly up/down-regulated in both NAC chemo-resistant tumors and cells compared to the sensitive tumors and wild-type cells. Through LASSO regression, we obtained a risk model composed of 12 genes. The risk model divided patients into high and low-risk groups. Univariate and multivariate Cox regression analyses suggested that the risk score is an independent prognostic factor for evaluating NAC response in breast cancer. Tumors in risk groups exhibited significant differences in molecular biological characteristics, tumor-infiltrating lymphocytes, and immunosuppressive molecule expression. Our results suggested that the risk score was also a good prognostic factor for breast cancer. Finally, we screened potential drugs that could reverse chemotherapy resistance in breast cancer. A novel 12 gene-signature could be used to predict NAC response and predict prognosis in breast cancer.

Insulin-like growth factor 2 receptor is a key immune-related gene that is correlated with a poor prognosis in patients with triple-negative breast cancer: A bioinformatics analysis

Immunotherapy plays an important role in the treatment of triple-negative breast cancer (TNBC). This study aimed to identify immune-related genes that are associated with the prognosis of patients with TNBC as possible targets of immunotherapy, alongside their related tumor-infiltrating lymphocytes (TILs). The clinical data and gene expression profiles of patients with breast cancer were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and divided into training (n = 1,053) and verification (n = 508) groups. CIBERSORT was used to predict the differences in immune cell infiltration in patient subsets that were stratified according to risk. Gene Ontology (GO) enrichment analysis was used to identify pathways associated with immune-related genes in patient subsets that were stratified according to risk. The clinical data and insulin-like growth factor 2 receptor (IGF2R) expression profiles of patients with breast cancer were extracted from METABRIC. The expression of IGF2R and TILs were evaluated in a cohort containing 282 untreated patients with TNBC. The correlations of IGF2R expression, TILs, and clinicopathological parameters with patient prognosis were analyzed in the whole cohort. The prognostic model, which was composed of 26 immune-related gene pairs, significantly distinguished between high- and low-risk patients. Univariate and multivariate analyses indicated that the model was an independent prognostic factor for breast cancer. Among the identified genes, the expression of IGF2R significantly distinguished between high- and low-risk patients in TCGA (P = 0.008) and in METABRIC patients (P < 0.001). The expression of IGF2R was significantly associated with clinical risk factors such as TNBC, estrogen receptor (ER)-negative expression, human epidermal growth factor receptor 2 (HER2)-positive expression, and age ≤60 years old in METABRIC patients. In addition, the patients with IGF2R-positive expression had lower disease-free survival (DFS) rates than those with IGF2R-negative expression in the TNBC cohort (67.8% vs. 78.5%, P = 0.023). IGF2R expression also was significantly negatively correlated with TILs, particularly with CD8+ TILs and CD19+ TILs in the cohort of patients with TNBC. IGF2R can be used as an indicator of a poor prognosis in patients with TNBC and as a potential target and research direction for TNBC immunotherapy in the future.

Effect of the use of prediagnosis hormones on breast cancer prognosis: MCC-Spain study.

To extend knowledge about the long-term use of hormones in hormone therapy or oral contraception as prognostic factors in breast cancer. The MCC-Spain project is a cohort of 1,685 women with incident breast cancer recruited in Spain. Recruitment was carried out between 2007 and 2010, and the follow-up finished in December 2017. The impact of hormone therapy or oral contraception on breast cancer prognosis was analyzed considering year of birth and menopausal status (1,095 women [65%] were postmenopausal). Hazard ratios (HRs) were estimated using Cox regression models. Death by any cause was considered as the event, and hormone therapy or oral contraception were analyzed as regressors. Oral contraception use for less than 5 years shows an HR of 1.10 (95% CI, 0.75 to 1.62), whereas use for 5 or more years shows an HR of 1.46 (95% CI, 0.95 to 2.25), with a P trend of 0.01, showing a dose-dependent response. Regarding hormone therapy and restricting the analysis to postmenopausal women born between1940 and 1959, where most hormone therapy (consumption) is concentrated, the results did not show any trend. Concerning oral contraception use, our results demonstrate that their use is related to poor prognosis in breast cancer. However, research in this field is limited and controversial, indicating the need for more research in this area. Regarding hormone therapy consumption, our results indicate no association with better prognosis, which contradicts what has previously been published.

Quantitative Assessment of Restriction Spectrum MR Imaging for the Diagnosis of Breast Cancer and Association With Prognostic Factors.

Restriction spectrum imaging (RSI) is an advanced quantitative diffusion-weighted magnetic resonance imaging (DWI) technique to assess breast cancer. To investigate the ability of RSI to differentiate the benign and malignant breast lesions and the association with prognostic factors of breast cancer. Retrospective. Seventy women (mean age, 49.6 ± 12.3 years) with 56 malignant and 19 benign breast lesions. 3-T; RSI-based DWI sequence with echo-planar imaging technique. The apparent diffusion coefficient (ADC) and RSI parameters (restricted diffusion f1 , hindered diffusion f2 , free diffusion f3 , and signal fractions f1 f2 ) were calculated by two readers for the whole lesion volume and compared between the benign and malignant groups and the subgroups with different statuses of prognostic factors in breast cancer. Mann-Whitney U test or Student's t-test was applied to compare the quantitative parameters between the different groups. Intraclass correlation coefficient (ICC) was used to assess readers' reproducibility. Binary logistic regression was used to combine parameters. Area under the curve (AUC) of receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of parameters to distinguish benign from malignant breast lesions. A P-value <0.05 was considered statistically significant. Malignant breast lesions showed significantly lower ADC and f3 values, and significantly higher f1 and f1 f2 values than the benign lesions, with AUC of 0.951, 0.877, 0.868, and 0.860, respectively. When RSI-derived parameters and ADC were combined, the diagnostic performance was superior to either single parameter (AUC=0.973). The f3 value was significantly differed between estrogen receptor (ER)-positive and ER-negative tumors. The ADC, f1 , f3 , and f1 f2 values were significantly different progesterone receptor (PR)-positive and PR-negative status. The RSI-derived parameters (f1 , f3 , and f1 f2 ) may facilitate the differential diagnosis between benign and malignant breast lesions. 4 TECHNICAL EFFICACY: Stage 2.

EVI1 expression in early-stage breast cancer patients treated with neoadjuvant chemotherapy

BackgroundOverexpression of the EVI1 (ecotropic viral integration site 1) oncogene has recently been implicated as a prognostic factor in breast cancer (BC), particularly in triple-negative BC (TNBC). In this study we aimed to investigate frequency and clinical relevance of EVI1 expression in newly diagnosed BC treated with neoadjuvant chemotherapy.MethodsEVI1 expression was determined by immunohistochemistry using H-score as a cumulative measurement of protein expression in pretherapeutic biopsies of BC patients treated with anthracycline/taxane based neoadjuvant chemotherapy within the GeparTrio trial. EVI1 was analyzed as a continuous variable and dichotomized into low or high based on median expression. Endpoints were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS).ResultsOf the 993 tumors analyzed, 882 had available subtype information: 50.8% were HR + /HER2-, 15% HR + /HER2 + , 9.8% HR-/HER2 + , and 24.5% TNBC. Median EVI1 H-score was 112.16 (range 0.5–291.4). High EVI1 expression was significantly associated with smaller tumor size (p = 0.002) but not with BC subtype. Elevated EVI1 levels were not significantly associated with therapy response and survival in the entire cohort or within BC subtypes. However, TNBC patients with high EVI1 showed a trend towards increased pCR rates compared to low group (37.7% vs 27.5%, p = 0.114; odds ratio 1.60 (95%CI 0.90–2.85, p = 0.110) and numerically better DFS (HR = 0.77 [95%CI 0.48–1.23], log-rank p = 0.271) and OS (HR = 0.76 [95% 0.44–1.31], log-rank p = 0.314) without reaching statistical significance.ConclusionEVI1 was not associated with response to neoadjuvant therapy or patient survival in the overall cohort. Further analyses are needed to verify our findings especially in the pathological work-up of early-stage HER2-negative BC patients.Trial registrationNCT00544765.

Real-world outcomes for Chinese breast cancer patients with tumor location of central and nipple portion.

BackgroundThe association between tumor location and breast cancer prognosis has been controversial. We sought to explore the relationship between tumors located in central and nipple portion (TCNP) and Chinese breast cancer.Patients and methodsA total of 1,427 breast cancer patients were recruited. There were 328 cases of TCNP and 1,099 cases of tumors in the breast peripheral quadrant (TBPQ). The chi-square test was used to compare different variables between TCNP and TBPQ groups. A one-to-one propensity score matching (PSM) was applied to construct a matched sample consisting of pairs of TCNP and TBPQ groups. Kaplan–Meier curves were used for survival analysis of disease-free survival (DFS), breast cancer-specific survival (BCSS) and overall survival (OS). The Cox proportional hazards regression model was applied to identify prognostic risk factors.ResultsThe median follow-up time was 58 months. Compared to TBPQ, TCNP patients had significantly larger tumor size, more frequent metastasis to lymph nodes (LN) and more proportions of TNM stage II–III. DFS, OS and BCSS rates were markedly lower in the TCNP group as compared to the TBPQ group before and after PSM (all p < 0.05). Multivariate Cox analysis showed that TCNP was an independent prognostic factor for breast cancer. Subgroup analysis indicated that for breast molecular subtypes and TNM stage II-III breast cancer, TCNP were related to worse prognosis. Multivariate logistic regression revealed that TCNP was an independent contributing factor for LN metastasis.ConclusionIn Chinese breast cancer, compared to TBPQ, TCNP is associated with more LN metastasis and poorer prognosis.

CD47 expression and tumor-associated immune cells in breast cancer and their correlation with molecular subtypes and prognostic factors.

Breast cancer is the most common malignancy in women and a heterogeneous disease at the molecular level. Since most breast cancer cases are not of a special type, it is suggested that tumor-associated macrophages and tumor-infiltrating lymphocytes, which are involved in tumor growth, invasion, angiogenesis, and metastasis, may be important factors that should be evaluated together with standard criteria to determine the prognosis of cancer and assist in treatment decisions and outcome stratification. In this study, CD47 expression, which is involved in macrophage-mediated immune escape, tumor-infiltrating lymphocytes, and tumor-associated macrophages were evaluated in breast cancer molecular subgroups and correlated with prognostic factors. The immunohistochemistry of CD47, CD163, and CD3 was analyzed on the tissue microarrays of 278 invasive breast cancer cases. The CD47, CD163, and CD3 expressions were found to be correlated with various clinicopathological parameters in breast cancer. High levels of CD47, CD163, and CD3 expressions had a significant correlation with the ER status and PR status, Ki-67 proliferation index, and molecular subtype (P<0.05). The CD47 expression had a significant correlation with the CD3 and CD163 expressions (p=0.021 and p=0.001, respectively). Our results suggest that CD47, CD163, and CD3 may be among the prognostic factors of breast cancer. The combined use of CD47, CD163, and CD3 can be a new prognostic factor for patients with breast cancer, especially as a therapeutic target in hormone receptor-negative breast cancer cases and those with a high proliferation index.

Hsa_circ_0097922 promotes tamoxifen resistance and cell malignant behaviour of breast cancer cells by regulating ACTN4 expression via miR-876-3p.

An increasing number of findings have verified the critical roles of circular RNAs (circRNAs) in human cancers, and chemotherapy resistance is a poor prognostic factor for breast cancer (BC). This study is designed to explore the function of hsa_circ_0097922 in the tamoxifen resistance of breast cancer. Hsa_circ_0097922, microRNA-876-3p (miR-876-3p), and alpha-actinin 4 (ACTN4) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell survival, proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry, wound healing and Transwell assays. Protein levels of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2), cleaved caspase 3, matrix metalloproteinase 9 (MMP9), and ACTN4 were determined using western blot assay. Using bioinformatics software, the binding between miR-876-3p and hsa_circ_0097922 or ACTN4 was predicted, followed by confirmation by RNA immunoprecipitation (RIP) and RNA pull-down assays. A xenograft tumour model in vivo analysed the biological role of hsa_circ_0097922 on BC tumour growth and drug resistance. Hsa_circ_0097922 and ACTN4 were increased, and miR-876-3p was decreased in tamoxifen resistance BC cells. Moreover, hsa_circ_0097922 knockdown can block BC cell malignant behaviour and tamoxifen resistance in vitro. Mechanically, hsa_circ_0097922 acted as a sponge of miR-876-3p to regulate ACTN4 expression. Hsa_circ_0097922 silencing increased the drug sensitivity of BC in vivo. Hsa_circ_0097922 might regulate BC cell malignant behaviour and tamoxifen resistance partly by regulating the miR-876-3p/ACTN4 axis, hinting at a promising therapeutic target for the BC treatment.