A New Model Including AMH Cut-off Levels to Predict Post-treatment Ovarian Function in Early Breast Cancer: A Prospective Cohort Study.

BACKGROUND: Breast cancer (BC) treatment decreases fertility capacity, but unnecessary fertility preservation procedures in women who would not be infertile after treatment would be a waste of time and resources and could cause the unwarranted exposure of cancer cells to exogenous sex hormones. It has been largely shown that post-treatment ovarian reserve is directly associated with pre-treatment anti-mullerian hormone levels (AMH0). A threshold for AMH0, or a model including AMH0 and patient characteristics that could distinguish the patients who will be infertile after treatments, still needs to be defined. Accordingly, this study was performed to specifically target this high-priority concern. METHODS: Women≤45 years old with newly diagnosed non-metastatic BC were entered in this multicenter prospective cohort study. AMH0 and two-year post-treatment AMH (AMH2) were measured, and hormonal patient features were recorded as well. Receiver operating characteristic (ROC) curve analysis, decision tree (DT), and random forest analyses were performed to find a cut-off point for AMH0 and define a model involving related features for the prediction of AMH2. RESULTS: The data from 84 patients were analyzed. ROC curve analysis revealed that AMH0>3 ng/mL (Area under the curve=0.69, 95% CI: 0.54‒0.84) was the best indicator for predicting AMH2≥0.7 (sensitivity=79%, specificity=60%). The best model detected by DT and random forest for predicting an AMH2>0.7 with a probability of 93% consisted of a combination of AMH0>3.3, menarche age<14, and age<31. CONCLUSION: This combination model can be used to withhold fertility preservation procedures in BC patients. Performing larger studies is suggested to further test this model.

Comparison of the Effect of 2 Virtual Education Methods: Family-based Versus Peer-Support on Perceived Stress and Stress Coping in Women with Breast Cancer: A Randomized Controlled Trial.

Background: Stress is an overwhelming feeling in patients with breast cancer (BC). However, The effect of virtual education has not been fully regulated. Hence, this study intends to compare the impact of 2 virtual education methods on perceived stress and stress coping in women with BC. Methods: A 3-armed randomized clinical trial was conducted among 315 women with BC who were referred to the Cancer Institute in Tehran. They were randomly assigned to 3 groups: (a) Family-based, receiving family-based training package; (b) peer-support, receiving peer-support educational package; and (c) control, receiving routine hospital care. Data were collected through demographic and disease characteristics, the Perceived Stress Scale (PSS-14), and Coping Inventory for Stressful Situations (CISS-21) questionnaires before and 3 months after the intervention. Results: The effect of the group factor after controlling the before-intervention scores in perceived stress, problem-oriented, emotion-oriented, and avoidance-oriented strategies were P < 0.0001, P = 0.015, P < 0.0001, and P = 0.111, respectively. Also, the effect of the confounding factor of BC disease stage in the dependent variables was P = 0.527, P = 0.275, P = 0.358, and P = 0.609, respectively. The effect size test showed that before the intervention, the mean scores of perceived stress, problem-oriented, emotion-oriented, and avoidance-oriented strategies were 32.00 ± 7.03, 19.36 ± 4.68, 25.10 ± 5.90, and 17.65 ± 6.64 respectively, but after the intervention showed a decrease in mean scores of perceived stress, emotion-oriented, and avoidance strategies. Conclusion: What is vibrant in virtual family-based education is far more effective than peer support when problem-oriented coping increases. Conversely, reducing perceived stress in women with BC receiving enough information and family support should be considered.

Thoracic duct identification with indocyanine green fluorescence to prevent chyle leaks during minimally invasive esophagectomy.

INTRODUCTION: Chylothorax (CT) is a rare yet serious complication after esophagectomy. Identification of the thoracic duct (TD) during esophagectomy is challenging due to its anatomical variation. Real-time identification of TD may help to prevent its injury. Near infra-red imaging with Indocyanine green (ICG) is a novel technique that recently has been used to overcome this issue. METHODS: Patients who underwent minimally invasive esophagectomy for esophageal cancer were divided into two groups with and without ICG. We injected ICG into bilateral superficial inguinal lymph nodes. Identification of TD and its injuries during the operation was evaluated and compared with the non-ICG group. RESULTS: Eighteen patients received ICG, and 18 patients underwent surgery without ICG. Each group had one (5.5%) TD ligation. In the ICG group injury was detected intraoperative, and ligation was done at the site of injury. In all cases, the entire thoracic course of TD was visualized intraoperatively after a mean time of 81.39 min from ICG injection to visualization. The Mean extra time for ICG injection was 11.94 min. In the ICG group, no patient suffered from CT. One patient in the non-ICG group developed CT after surgery that was managed conservatively. According to Fisher's exact test, there was no significant association between CT development and ICG use, possibly due to the small sample size. CONCLUSIONS: This study confirms that ICG administration into bilateral superficial inguinal lymph nodes can highlight the TD and reduce its damage during esophagectomy. It can be a standard method for the prevention of postoperative CT.

Inhibition of breast cancer cell growth and migration through siRNA-mediated modulation of circ_0009910/miR-145-5p/MUC1 axis.

Circular RNAs (circRNAs) characterize a novel kind of regulatory RNAs distinguished by great evolutionary conservation and constancy. Although their exact role in malignancies is not fully understood, they mainly work through specific axes. Circular RNA/miRNA/mRNA axes affect the pathogenesis of human cancers including breast cancer. We assessed the expression and function of circ_0009910/miR-145-5p/MUC1 axis in Breast Cancer tissues and MCF-7 cells. Expression levels of circ_0009910 and MUC1 were notably increased in breast cancer tissues compared with control tissues, parallel with the down-regulation of miR-145-5p. Clinicopathological analysis indicated that up-regulation of circ_0009910 in breast tumors is related to invasion of the tumor to lymph node (P value = 0.011). Also, the downregulation of miR-145-5p was significantly correlated with tumor invasion to lymph nodes (P value = 0.04) and HER2-negative tumors (P value = 0.037). Finally, overexpression of MUC1 was correlated with age under 45 years (P value = 0.002). More importantly, circ_0009910-siRNA decreased the proliferation and migration ability of breast cancer cells, enhanced expression of miR-145-5p, and decreased levels of MUC1. Taken together, the circ_0009910/miR-145-5p/MUC1 axis has been demonstrated to affect the pathogenesis of breast cancer and might provide a target for breast cancer treatment.

The association of metformin and aspirin intake with mammographic breast density: A cross-sectional study.

Background: Our purpose was to investigate the association between Mammographic breast density (MBD), a known strong marker for breast cancer and metformin and aspirin use and duration of use alone or simultaneously, in a sample of Iranian women considering other confounding factors. Methods: In a cross-sectional study, 712 individuals were selected out of women referred to two university hospitals for screening mammography. Participants' information was collected with a questionnaire. Four-category density scale (a = almost entirely fatty, b = scattered fibroglandular densities, c= heterogeneously dense, and d = extremely dense) was categorized as low (a&b) and high (c&d) density. Results: The mean age of the participants was 49.80 ± 7.26 years. Sixty-five percent of women belonged to the high and 35% to the low MBD category. Both aspirin and metformin had a significantly negative association with MBD, however, when confounding factors were entered into the models, only aspirin after adjustment for age and BMI had an inverse association with MBD (OR = 0.53, 95% CI: 0.35-0.94). Simultaneous use of metformin and aspirin (OR = 0.44, 95 %CI: 0.17-1.12) was associated with lower MBD. Furthermore, in women who used metformin (OR = 0.23, 95% CI: 0.09-0.62) and aspirin (OR= 0.35, 95% CI: 0.17-0.72) for 2 to 5 years, MBD was significantly lower. However, after the adjustment of confounding factors, these associations were not statistically significant. Conclusion: It seems metformin and aspirin intakes are associated with MBD. However, further studies with more sample size are needed.

Evaluation of HER2 Positivity Based on Clinicopathological Findings in HER2 Borderline Tumors in Iranian Patients with Breast Cancer.

Background & Objective: Human epidermal growth receptor-2 (HER2) gene amplification is an important predictive and prognostic factor in breast cancer treatment. However, the expression of HER2 determined by immunohistochemistry (IHC) is considered as borderline in some cases, and confirmation of the HER2 status by either fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) is necessary for correct treatment decision-making. Considering the high cost of FISH and CISH, we aimed to investigate whether clinicopathological findings of the tumor could predict the HER2 status. Methods: A retrospective study was performed using the data from 584 patients with breast cancer with HER2-borderline disease, confirmed by IHC. Final HER2 status, pathologic tumor size and type, nodal involvement, Ki67 index, presence of estrogen and progesterone receptors (ER, PR), lymphovascular invasion (LVI), and stage were retrieved from the clinical records. Results: One hundred twenty-one (20.7%) patients were HER2-positive according to the FISH or CISH results. Logistic regression analysis showed that the pathologic size was positively associated with HER2 positivity with an odds ratio (OR) of 1.02 (95% CI: 1.01-1.04). In addition, the adjusted OR illustrated a statistically significant association between HER2 positivity and PR negativity (OR= 2.22, 95% CI: 1.29-3.83). Conclusion: In HER2 borderline breast cancer, HER2 positivity significantly increases with tumor size and PR negativity. Further studies are recommended that may find an applicable model to predict the actual status of HER2 in borderline cases.

Fatty acid profiles and Delta9 desaturase (stearoyl-CoA desaturase; SCD 1) expression in adipose tissue surrounding benign and malignant breast tumors.

The progression of tumors occurs through interactions between the tumor and the stroma. Understanding the role of adipose tissue (AT), as the main component of the breast tumor microenvironment (TME) in the development of cancer, is crucial for the early detection of breast cancer (BC). This study compared the FA profiles, desaturase index (DI), and stearoyl CoA desaturase 1 (SCD1) mRNA levels in the AT that surrounds tumors in women with BC and benign breast disease (BBD). Specimens were collected from 40 Iranian women who had undergone breast surgery. These women were age- and BMI-matched and were divided into two groups: BC (n = 20) and BBD (n = 20). Gas chromatography and quantitative real-time PCR were used to analyze the FA profiles and SCD1 mRNA levels, respectively. The DI was calculated by dividing the amounts of monounsaturated FAs by the amount of saturated FA. There were no significant differences in age and BMI between women with BC and BBD. The FA profiles and DI were also similar in both groups. However, mRNA levels of SCD1 were found to be 5 times higher in the breast AT of BC than in the breast AT of BBD (p < 0.0001). We showed that SCD1 was significantly upregulated in the AT surrounding BC tumors, even though the DI and FA profiles were unchanged compared to those in the AT of BBD patients. It is important to note that the breast AT of women with BBD has previously been overlooked and warrants further studies.

Clinical characteristics of breast cancer patients admitted to academic surgical wards in Tehran, Iran: an analytical cross-sectional study.

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer death among women. Knowledge of the clinical characteristics of BC in a population may be informative for disease prediction or diagnosis and for developing screening and diagnostic guidelines. This study aimed to evaluate the clinical characteristics of female patients with BC who were admitted to academic surgical wards in Tehran, Iran. METHODS: In this cross-sectional study, demographic information and clinical characteristics of Iranian females with BC who had undergone breast surgery from 2017-2021 in four academic Breast Surgery Units were extracted from medical files and recorded via a pre-designed checklist. RESULTS: A total of 1476 patients with a mean age of 48.03 (± 11.46) years were enrolled. Among them, 10.4% were aged less than 35. In younger patients, Triple-negative and Her2-enriched subtypes of BC were significantly higher compared to older ones. Overall, 85.7% of tumors were invasive ductal carcinoma, 43.3% were grade 2, 41.4% were located in the UOQ, and 65.2% had presented with mass palpation. The mean pathologic tumor size was 28.94 mm, and the most common subtype was luminal B. CONCLUSIONS: Many characteristics of breast cancer in this study were similar to other countries and previous studies in Iran. However, a higher proportion of young BC compared with Western countries, and even with older studies in Iran, suggest a trend toward lower age for BC in recent years. These results indicate the need for preventive measures and screening in Iranian women at a younger age.

Abbreviated breast MRI for evaluating breast cancer before initiation of neoadjuvant chemotherapy: A cross-sectional study.

Background: Although, there are accumulating evidence about diagnostic role of abbreviated breast magnetic resonance imaging (MRI) in screening setting, the implementation of abbreviated MRI in staging of breast cancer has been poorly elucidated. Objective: To evaluate the diagnostic performance of abbreviated breast MRI in estimating extent of disease before initiation of neoadjuvant chemotherapy. Methods: A total of 54 patients with biopsy-proven main lesion referred to evaluate by standard protocol breast MRI before initiation of neoadjuvant chemotherapy were retrospectively enrolled. From a standard protocol, a data set of abbreviated protocol consisting fat-saturated T1-weighted (T1W) pre-contrast and first two fat-saturated T1W post-contrast series with reconstruction of their subtraction including maximum intensity projection (MIP) were obtained and interpreted. The concordance rate of abbreviated with standard protocol (as a reference standard) were compared. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive value were calculated, as well. Results: The maximum size of the main mass was 38.6 ± 17.3 and 40.7 ± 17.9 for abbreviated and standard protocol, respectively. All of the main mass was detected by abbreviated protocol with 100% concordance. Concordance was 98.1% and 94.4% in terms of multifocal/multicentric status and for estimating of NME, respectively. The abbreviated protocol has high sensitivity and specificity with more than 90% value regarding main mass detection, measurement of the maximum size of the main mass, determination of multifocal/multicenter status and NAC involvement. Conclusion: Abbreviated protocol may be a reliable surrogate for standard protocol breast MRI in evaluating extent of breast cancer.

A pilot study of the use of human amniotic membrane as subcutaneous implants in a mouse model: a potential for temporary substitutes in two-stage breast reconstructions.

INTRODUCTION: Breast reconstruction by prosthesis is frequently performed in breast cancer treatments, and a temporary substitute is used in the first step of two-stage operations. AIM: Due to the advantageous biological features of the human amniotic membrane, we aimed to evaluate its use for temporary implants. METHOD: We prepared small spherical implants from human amniotic membranes and inserted them into BALB/c mice's subcutaneous flanks. Then, we compared the bulging they produced, the durability, and the host reaction with implants made from the chorionic membrane, folded membrane patches, and sterile plastic beads. RESULTS: All amionitic cases were healthy throughout the study and only mild inflammation occurred in them. Furthermore, the bulging of the implants was acceptable and faded gradually. However, moderate inflammation was observed in chorionic implant mice, and the bulging disappeared very soon. Finally, the control group had severe inflammation and the beads implant was rejected. CONCLUSION: Our study showed that the human amniotic membrane could represent a safe and valid tool for breast reconstruction, however, further studies on larger animals and more implants are suggested.

SBF2-AS1 and TreRNA: novel lncRNA players in triple-negative breast cancer pathogenesis.

BACKGROUND: Compared to other breast cancer subtypes, triple-negative breast cancer (TNBC) has always been challenging for clinicians due to its aggressive behavior and lack of a specific treatment. There is a confirmed association between invasive features of tumors and increased epithelial-mesenchymal transition (EMT) process, which is consistent with a higher rate of EMT in TNBC. METHODS AND RESULTS: We investigated the expression of EMT-related genes, SNAI1 and MMP7, and EMT-related lncRNAs, treRNA and SBF2-AS1, in 50 TNBC tumors and 50 non-TNBC tumors to reveal more regulators and effectors involved in TNBC malignancy. In the present study, we showed the overexpression of all the studied genes and lncRNAs in TNBC tumors compared to non-TNBC samples. Moreover, a significant association was observed between MMP7 and treRNA expression levels and larger tumor size. A positive correlation between SNAI1 and lncRNA treRNA expression levels was also detected. CONCLUSIONS: Due to the differential expression and the potential diagnostic power of the studied genes, SBF2-AS1 and treRNA can be proposed as new probable biomarkers and therapeutic targets in TNBC.

Application of Breast Scintigraphy for Patients with Suspicious (Breast Imaging-Reporting and Data System IV) Breast Lesions.

Background: The surgery for a breast imaging-reporting and data system (BIRADS) IV lesions needs imaging or pathology supporting data. The roll of breast scintigraphy for this purpose is unclear. Materials and Methods: In a prospective design, 16 patients with 25 BIRADS IV lesions who were scheduled for surgery were included. Before the surgery, breast scintigraphy was done using a nondedicated dual head gamma camera in the prone position employing a shaped foam pad providing imaging at breast pendulous position. Twenty mCi99m Tc methoxy-isobutyl-isonitrile was injected and two 15 and 60-min delayed imaging were done (anterior, bilateral, and single photon emission computed tomography [SPECT] projections). Pathology reports were collected and tumor to nontumor uptake ratio (T/NT) was analyzed, accordingly. Results: Out of all lesions, 12 were malignant (invasive ductal and lobular carcinoma ductal carcinoma in situ). At 15 min, T/NT was insignificantly higher in the malignant compared to benign lesions (22.8 ± 23.9 vs. 10.1 ± 10.1; P = 0.109). The optimal T/NT cutoff for discrimination of malignant and benign lesions was 20. Only 1 out of 13 benign lesions presented uptake >20 (7.7%; false-positive rate; P = 0.047). The diagnostic accuracy, sensitivity, and specificity for T/NT calculated at 0.68, 0.42, and 0.92, respectively. The T/NT at 60 min remained unchanged for either benign or malignant lesions (22.3 ± 30.2 vs. 11.7 ± 17.1; P = 0.296). Conclusions: Breast scintigraphy with general purpose gamma camera employing SPECT imaging may assist the selection of BIRADS IV lesions in need for surgery. All uptake positive cases should undergo surgery and decision for uptake negative cases should be made based on other data.

Clinical Breast Cancer Registry of IR. Iran (CBCR-IR): Study Protocol and First Results.

BACKGROUND: Breast cancer (BC), as a significant global health problem, is the most common cancer in women. Despite the importance of clinical cancer registries in improving the quality of cancer care and cancer research, there are few reports on them from low- and middle-income countries. We established a multicenter clinical breast cancer registry in Iran (CBCR-IR) to collect data on BC cases, the pattern of care, and the quality-of-care indicators in different hospitals across the country. METHODS: We established a clinical cancer registry in 12 provinces of Iran. We defined the organizational structure, developed minimal data sets and data dictionaries, verified data sources and registration processes, and developed the necessary registry software. During this registry, we studied the clinical characteristics and outcomes of patients with cancer who were admitted from 2014 onwards. RESULTS: We registered 13086 BC cases (7874 eligible cases) between 1.1.2014 and 1.1.2022. Core needle biopsy from the tumor (61.25%) and diagnostic mammography (68.78%) were the two most commonly used diagnostic methods. Stage distribution was 2.03% carcinoma in situ, 12% stage I, 44.65% stage II, 21.32% stage III, and 4.61% stage IV; stage information was missing in 1532 patients (19.46%). Surgery (95.01%) and chemotherapy (79.65%) were the most common treatments for all patients. CONCLUSION: The information provided by this registry can be used to evaluate and improve the quality of care for BC patients. It will be scaled up to the national level as an important resource for measuring quality of care and conducting clinical cancer research in Iran.

Breast Cancer Sentinel Lymph Node Detection Rate: First Large Scale Multi-Centric Data for Technetium Phytate.

BACKGROUND: Sentinel lymph node biopsy (SLNB) with injection of radiopharmaceuticals is now the standard of care for staging the axilla in patients with breast cancer. Sulfur or antimony colloids labeled with 99mTechnetium (Tc) are used globally for the procedure, with a detection rate of 94%. However, in Iran, Tc phytate has been used because it is more easily producible in the country. The detection rate with Tc phytate has not been well determined in large-scale studies. Objective: We performed this study to report the detection rate of SLNB with Tc phytate, its advantages and disadvantages using large multicentric data. METHODS: This is a retrospective cross-sectional multicenter study. Participants were breast cancer patients without previous history of axillary surgery, who underwent sentinel node biopsy using Tc phytate on the morning of surgery or the day before. The detection rate was calculated as the number of patients with histologically positive sentinel nodes to all patients with histologically positive lymph nodes; we compared those injected on the day of surgery and those injected on the day before. RESULTS: Overall, 2663 women aged 50.2±11.6 years were included. The detection rate was 91.8% (806 out of 878). The false negative rate was 8.2% overall, and statistically similar for injections on the day or the day before surgery (2.9 vs 2.1; P=0.32). CONCLUSION: Tc phytate has a good detection rate for breast radio-guided SLNB with similar result for injections on the surgery day or the day before it.

Feasibility of measuring comorbidity indices based on clinical breast cancer records.

Background: Comorbidities have a significant impact on the treatment and outcome of breast cancer. However, data on such comorbidities from low-income countries are limited. Aim: To evaluate the feasibility and accuracy of comorbidity data extracted from medical records for estimating the prevalence of comorbidities among patients registered in the clinical breast cancer registry of the Islamic Republic of Iran. Methods: We collected data from the medical records of 400 patients on 30 comorbidities included in the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). The sensitivity and specificity of comorbidity data extracted from medical records were calculated using data from interviews with 97 randomly selected patients. We studied the prevalence of comorbidities using the CCI and ECI. Data were analysed using SPSS version 24. Results: The mean age of patients was 51.69 SD 12.28 years. The sensitivity and specificity of medical records for detecting any comorbidity data contained in CCI versus non-comorbidity were 93.2% and 69.8%, respectively. However, for the comorbidity data included in ECI, both sensitivity (86.9%) and specificity (44.4%) were lower than in CCI. Hypertension (n = 144, 36.0%) and diabetes without chronic complications (n = 77, 19.3%) were the most prevalent comorbidities. A higher proportion of patients had no comorbidity with CCI (72.2%) than with ECI (44.8%). Conclusion: It is feasible to construct a comorbidity index using medical records with high accuracy, especially when we extract comorbidities using the CCI. Further studies are needed to understand the association between comorbidity index and breast cancer survival among Iranian patients.

Air pollution exposure and mammographic breast density in Tehran, Iran: a cross-sectional study.

BACKGROUND: Air pollution is one of the major public health challenges in many parts of the world possibly has an association with breast cancer. However, the mechanism is still unclear. This study aimed to find an association between exposure to six criteria ambient air pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and mammographic breast density (MBD), as one of the strongest predictors for developing breast cancer, in women living in Tehran, Iran. METHODS: Participants were selected from women attending two university hospitals for screening mammography from 2019 to 2021. Breast density was rated by two expert radiologists. Individual exposures to 3-year ambient air pollution levels at the residence were estimated. RESULTS: The final analysis in 791 eligible women showed that low and high breast density was detected in 34.8 and 62.2 of participants, respectively. Logistic regression analysis after considering all possible confounding factors represented that an increase in each unit of NO2 (ppb) exposure was associated with an increased risk of breast density with an OR equal to 1.04 (95CI: 1.01 to 1.07). Furthermore, CO level was associated with a decreasing breast density (OR = 0.40, 95CI = 0.19 to 0.86). None of the other pollutants were associated with breast density. CONCLUSION: Higher MBD was associated with an increased level of NO2, as a marker of traffic-related air pollution. Furthermore, CO concentration was associated with a lower MBD, while other criteria air pollutants were not related to MBD. Further studies are needed to evaluate the association between ambient air pollutants with MBD.

Innovative targets of the lncRNA-miR-mRNA network in response to low-dose aspirin in breast cancer patients.

This study aimed to investigate innovative targets in breast cancer patients by considering the interaction of the lncRNA-miR-mRNA network in response to low-dose aspirin. The candidate miRs were first taken from the GEO and TCGA databases. Then, the candidate network was constructed using the high-throughput sequencing data. The expression levels of candidate targets were finally measured using Real-Time PCR in luminal A breast cancer patients undergoing aspirin (80 mg daily for three months) and non-aspirin groups during chemotherapy after surgery. The expression levels of TGFß, IL-17, IFNγ, and IL-ß proteins were measured using the ELISA technique. 5 lncRNAs, 12 miRs, and 10 genes were obtained in the bioinformatic phase. A significant expression increase of the candidate tumor suppressor lncRNAs, miRs, and genes and a substantial expression decrease of the candidate onco-lncRNAs, oncomiRs, and oncogenes were achieved after the aspirin consumption. Unlike the non-aspirin group, the expression levels of TGFß, IL-17, IFNγ, and IL-ß proteins were significantly decreased following aspirin consumption. The Kaplan-Meier analysis indicated a longer overall survival rate in the patients after aspirin consumption. Our results showed that the lncRNA-miR-mRNA network might be a significant target for aspirin; their expression changes may be a new strategy with potential efficacy for cancer therapy or prevention.

An innovative systematic approach introduced the involved lncRNA-miR-mRNA network in cell cycle and proliferation after conventional treatments in breast cancer patients.

The present study aimed to explore the involved lncRNA-miRNA-mRNA network in the cell cycle and proliferation after conventional treatments in Luminal A breast cancer patients.The candidate miRNAs (miRs), lncRNAs, and mRNAs were first taken from the Gene Expression Omnibus and TCGA databases. The lncRNA-miR-mRNA network was then constructed using the high-throughput sequencing data. The expression levels of selected targets were measured in the breast cancer and healthy samples by the Real-Time PCR technique and compared with the clinical outcomes by the Kaplan-Meier method.Our analysis revealed a group of differentially expressed 3 lncRNAs, 9 miRs, and 14 mRNAs in breast cancer patients. A significant expression decrease of the selected tumor suppressor lncRNAs, miRs, and genes and a substantial expression increase of the selected onco-lncRNAs, oncomiRs, and oncogenes were obtained in the patients compared to the healthy group. The plasma levels of the lncRNAs, miRs, and mRNAs were more significant after the operation, chemotherapy, and radiotherapy than the pre-treatment. The Kaplan-Meier analysis indicated that the patients with a high expression of miR-21, miR-20b, IGF1R, and E2F2 and a low expression of miR-125a, PDCD4, and PTEN had exhibited a shorter overall survival rate.Our results suggested that the underlying mechanisms of the lncRNA, miRs, and mRNAs and relevant signaling pathways may be considered predictive and therapeutic targets for breast cancer.