Occurrence of Residual Breast Tumors and Efficacy of MRI in their Detection after Vacuum-assisted Excisional Biopsy.

BACKGROUND: Residual breast tumors may remain after vacuum-assisted excisional biopsy (VAEB). OBJECTIVE: To determine the incidence of residual breast tumors in patients after VAEB and the efficacy of magnetic resonance imaging (MRI) in detecting these tumors. METHODS: This retrospective analysis examined patients who received VAEB before a diagnosis of breast cancer (BC) at our hospital from 2015 to 2019. The incidence of residual tumors after VAEB was determined by MRI and pathological examination. The diagnostic value of MRI in detecting residual tumors was determined for all patients and different subgroups. Logistic regression analysis was used to identify factors associated with residual tumors. RESULTS: We examined 147 patients and obtained pathological samples from 146 patients, including 103 (70.5%) with residual tumors and 43 (29.5%) without residual tumors. The MRI examinations demonstrated the complete tumor resection rate was 48.9%. Compared to the pathological results, MRI had a positive predictive value of 77.8%, negative predictive value of 48.8%, specificity of 65.6%, and sensitivity of 60.7%. Further analysis indicated that MRI had moderate accuracies for patients with stage pT-1 (71.9%), stage pTNM-IA (73.1%), and luminal B subtype (78.3%). Binary logistic regression analysis showed that the risk of tumor residue correlated with the pathological stage. CONCLUSION: Tumor residue is common after VAEB, and MRI has limited accuracy in detecting these residual tumors. However, for small breast tumors and luminal B subtype BC, MRI had higher accuracy in the detection of residual tumors. The risk of tumor residue is closely associated with the pathological stage.

Three-axis angle measurement method based on an optical wedge.

A three-axis angle measurement method is proposed using an optical wedge as a reflector. In this paper, the mathematical model of three-axis angle solving corresponding to the method is derived, and it is verified and corrected by establishing an optical simulation model, and, finally, the feasibility and measurement accuracy of the method are verified by using a principle prototype. The experimental results show that the RMS values of the measurement errors of pitch angle α, yaw angle ß, and roll angle γ are 6.27 ' ' , 4.35 ' ' , and 17.68 ' ' , respectively, within the measurement range of ±2∘, and the measurement accuracy is insensitive to the measurement distance.

Analysis of neoadjuvant chemotherapy for breast cancer: a 20-year retrospective analysis of patients of a single institution.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been widely applied in operable breast cancer patients. This study aim to identify the predictive factors of overall survival(OS) and recurrence free survival (RFS) in breast cancer patients who received NAC from a single Chinese institution. PATIENTS AND METHODS: There were 646 patients recruited in this study. All the patients were treated at department of Surgical Oncology, Sir Run Run Shaw Hospital between February 25, 1999 and August 22, 2018. The relevant clinicopathological and follow-up data were collected retrospectively. RFS and OS were assessed using the Kaplan-Meier method. Multivariate Cox proportional hazards model was also employed. Multi-variate logistic regression model was simulated to predict pathologic complete response (pCR). RESULTS: In total, 118 patients (18.2%) achieved pCR during NAC. The 5-year OS was 94.6% versus 78.1% in patients with and without pCR, respectively (P < 0.001). The 5-year RFS was 95.3% and 72.7%, respectively (P < 0.001). No difference was detected among molecular subtypes of 5-year RFS in patients obtained pCR. Factors independently predicting RFS were HER2-positive subtype (hazard ratio(HR), 1.906; P = 0.004), triple-negative breast cancer (TNBC) (HR,2.079; P = 0.003), lymph node positive after NAC(HR,2.939; P < 0.001), pCR (HR, 0.396;P = 0.010), and clinical stage III (HR,2.950; P = 0.016). Multi-variate logistic regression model was simulated to predict the pCR rate after NAC, according to clinical stage, molecular subtype, ki-67, LVSI, treatment period and histology. In the ROC curve analysis, the AUC of the nomogram was 0.734 (95%CI,0.867-12.867). CONCLUSIONS: Following NAC, we found that pCR positively correlated with prognosis and the molecular subtype was a prognostic factor.

Development and validation of a nomogram for predicting internal mammary sentinel node metastasis in breast cancer patients.

OBJECTIVE: Internal mammary nodes are important in breast cancer prognosis, but their diagnosis is often missed in clinical practice, leading to inaccurate staging and treatment. We developed a validated nomogram to predict the presence of internal mammary sentinel nodes (IMSN) metastasis. METHODS: A total of 864 sequential IMSN biopsy procedures from a prospective studies database of 1505 cases were used for model development and validation. Multivariable logistic regression was performed on 519 sequential IMSN biopsy procedures from multi-center data between August 2018 and July 2022 to predict the presence of IMSN metastasis. A nomogram was developed based on the logistic regression model and subsequently applied to 345 sequential IMSN biopsy procedures from single-center data between November 2011 and July 2018. The model's discrimination was assessed using the area under the receiver operating characteristic curve. RESULTS: The overall frequency of IMSN metastasis was 17.0% in our study. A predictive model for IMSN metastasis was constructed using tumor size, tumor location, lymphovascular invasion, the number of positive axillary nodes (P < 0.05 for all variables in multivariate analysis), and histological grade (P < 0.05 only in univariate analysis). The nomogram was accurate, with a concordance index of 0.84 in the bootstrapping analysis and an area under the receiver operating characteristic curve of 0.80 in the validation population. CONCLUSION: Our nomogram provides an accurate and validated multivariable predictive model for estimating the individual likelihood of having IMSN metastasis. This may be useful for personalized treatment decisions regarding internal mammary radiotherapy in breast cancer patients.

Patients achieved pCR during neoadjuvant chemotherapy had better outcome than adjuvant chemotherapy setting in breast cancer: A comparative study.

PURPOSE: Pathological complete response(pCR) during neoadjuvant chemotherapy(NAC) has been proposed as a predictor for better prognosis in breast cancer. However, few studies compare the outcomes of patients receiving NAC and adjuvant chemotherapy(AC). METHODS: We retrospectively matched the patients who received NAC(N = 462) and AC(N = 462) by age, time of diagnosis, and primary clinical stage using the propensity score match in breast cancer patients treated in Sir Run Run Shaw Hospital with the median follow up of 67 months. Death from breast cancer and recurrence were used as endpoints. A multivariable Cox models were used to estimate the hazard ratios for breast-cancer specific survival (BCSS) and DFS. A multivariable logistic regression model was simulated to predict pCR. RESULTS: In patients who received NAC, 18.0%(83/462) patients achieved pCR, while the rest of the patients did not. pCR subgroup demonstrated significant better BCSS and DFS than patients receiving AC(BCSS: HR = 0.39, 95% CI:0.12-0.93, P = 0.03; DFS: HR = 0.16, 95%CI 0.009-0.73, P = 0.013) and non-pCR patients(BCSS: HR = 0.32, 95%CI 0.10-0.77, P = 0.008; DFS: HR = 0.12, 95%CI 0.007-0.55, P = 0.002). Patients who received AC demonstrated insignificant survival compared to non-pCR patients(BCSS: HR= 0.82, 95%CI 0.62-1.10, P = 0.19; DFS: HR = 0.75, 95%CI 0.53-1.07, P = 0.12). Patients with AC had significant better DFS than non-pCR patients(HR = 0.33, 95% CI 0.10-0.94, P = 0.04) in luminal B Her2+ patients. More NAC cycles(>2), TNBC, lower cT stage, and mixed histology indicate higher possibility of pCR(AUC = 0.89). CONCLUSION: pCR patients with NAC indicated better prognosis than patients receiving AC or non-pCR patients from NAC. The timing of chemotherapy may need carefully pondering in luminal B Her2+ patients.

The mediating role of appraisal on health-related quality of life in adolescent and young adult cancer survivors.

BACKGROUND: Adolescent and young adult (AYA) cancer survivors (first diagnosed with cancer at age 15-39) are distinct within the cancer community due to their unique challenges and diverse psycho-behavioral characteristics. This study aimed to analyze psycho-behavioral pathways and further explore the mediating role of cognitive appraisals on AYA cancer survivors' quality of life (QoL). METHODS: Three hundred and eighty-nine AYA cancer survivors were eligible for analyses and recruited to self-administer questionnaires on QoL (the Chinese version of EORTC Quality of Life Questionnaire-C30 v3.0), resilience, coping, and appraisal on site. This study performed structural equation modeling (SEM) to examine pathways on QoL based on the Rapkin & Schwartz QoL Appraisal Model. RESULTS: The average age of participants (47.6% female) was 32.7 ± 4.1 years. The SEM results closely fit the measured data (RMSEA = 0.053, GFI = 0.955, CFI = 0.964, SRMR = 0.052). The final model showed direct negative effects of later clinical-stage, more comorbidities, and more Acceptance-Resignation coping on QoL; indirect positive effects of better resilience on QoL through less Acceptance-Resignation coping (ß = 0.286, P = 0.002). Appraisal mediated the effects of treatment and resilience on QoL (ß = -0.024, P = 0.038). Further, Calm, Peaceful, and Active appraisal patterns were associated with improved Cognitive Functioning (ß = 0.119, P = 0.009). CONCLUSION: Appraisal, coping, and resilience could significantly mediate the effects of cancer and its treatment on the QoL of AYA cancer survivors. Future interventions targeting cognitive appraisals and psycho-behaviors will be helpful. Figuring out what matters to such a unique population and how they appraise a cancer diagnosis through treatment trajectories could help nurses adjust support.

Immune landscape and risk prediction based on pyroptosis-related molecular subtypes in triple-negative breast cancer.

The survival outcome of triple-negative breast cancer (TNBC) remains poor, with difficulties still existing in prognosis assessment and patient stratification. Pyroptosis, a newly discovered form of programmed cell death, is involved in cancer pathogenesis and progression. The role of pyroptosis in the tumor microenvironment (TME) of TNBC has not been fully elucidated. In this study, we disclosed global alterations in 58 pyroptosis-related genes at somatic mutation and transcriptional levels in TNBC samples collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Based on the expression patterns of genes related to pyroptosis, we identified two molecular subtypes that harbored different TME characteristics and survival outcomes. Then, based on differentially expressed genes between two subtypes, we established a 12-gene score with robust efficacy in predicting short- and long-term overall survival of TNBC. Patients at low risk exhibited a significantly better prognosis, more antitumor immune cell infiltration, and higher expression of immune checkpoints including PD-1, PD-L1, CTLA-4, and LAG3. The comprehensive analysis of the immune landscape in TNBC indicated that alterations in pyroptosis-related genes were closely related to the formation of the immune microenvironment and the intensity of the anticancer response. The 12-gene score provided new information on the risk stratification and immunotherapy strategy for highly heterogeneous patients with TNBC.

Efficacy and Safety of Mitoxantrone Hydrochloride Injection for Tracing Axillary Sentinel Nodes in Breast Cancer: A Self-Controlled Clinical Trial.

Background: Mitoxantrone hydrochloride injection for tracing (MHI), a new strategy to identify lymph nodes, has not been tested for axillary node staging in breast cancer. This multicenter, self-controlled, non-inferiority trial aimed to evaluate MHI's efficacy and safety in sentinel lymph node biopsy (SLNB). Methods: The trial was conducted across seven hospitals from December 2019 to December 2020. Patients with early-stage breast cancer received MHI and technetium-99m (99mTc) during the surgery. Sentinel node detection rates were compared between MHI and 99mTc to evaluate non-inferiority and concordance. Non-inferiority was valid if the lower limit of the 95% CI of sentinel node relative detection rate difference was ≥-5%. Results: SLN relative detection rate of MHI was 97.31% (362/372). Of the SLNs, 79.69% (871/1093) were co-detected by both tracers. Of the patients, 4.13% (16/387) had adverse events and recovered during the follow-up. Conclusions: MHI is a lymphatic tracer with comparable efficacy to radionuclides and can be used alone or in combination with radioactive substances for SLNB. Clinical Trial Registration: http://www.chinadrugtrials.org.cn, CTR20192435.

HER2 protein expression level is positively associated with the efficacy of neoadjuvant systemic therapy in HER2-positive breast cancer.

PURPOSE: The purpose of this study was to determine whether the HER2 protein expression level assessed by immunochemistry (IHC) was related to the treatment response in HER2-positive breast cancer patients who received neoadjuvant chemotherapy. PATIENTS AND METHODS: 167 HER2-positive breast cancer patients who had received neoadjuvant chemotherapy containing trastuzumab were included in this study. There were 27 HER2 2 + and 140 HER2 3 + cases. Using propensity score matching (PSM), the two groups were matched 1:3 by T stage, N stage, hormone receptor (HR) status, Ki67, and targeted therapy regimen. We performed univariate and multivariate analyses of the association between HER2 expression level and pathological complete response (pCR) rate. RESULTS: The overall pCR rate was 43.7% (73/167). The pCR rate in the HER2 3 + group was significantly higher than in the HER2 2 + group (47.9% versus 22.2%, p = 0.014). After propensity score matching, 26 patients in the HER2 2 + group and 59 patients in the HER2 3 + group were matched. The pCR rate in the HER2 3 + group was still higher than in the HER2 2 + group (50.8% versus 19.2%, p = 0.006). Multivariate analysis showed that HER2 protein expression was an independent predictive factor for pCR (OR=5.353, 95% CI 1.649-17.379, p = 0.005). Additionally, the Ki67 index was also a significant factor for pCR (OR=3.702, 95% CI 1.327-10.326, p = 0.012). CONCLUSION: For HER2-positive breast cancer patients, the HER2 protein expression level detected by IHC may be a good predictive factor for the efficacy of neoadjuvant chemotherapy.

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio and C-Reactive Protein/Albumin Ratio in Luminal Breast Cancers With HER2-Negativity.

Purpose: This study was determined to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR) prior to surgery in luminal breast cancers (BC) with HER2-negativity. Methods: The clinical data of 708 HER2-negative luminal BC patients from January 2013 to December 2016 were retrospectively collected and analyzed. The optimal cut-off value of NLR and CAR were determined via receiver operating characteristic (ROC) curve. The disease-free survival (DFS) and cancer specific survival (CSS) rates were estimated using the Kaplan-Meier method. Cox univariate and multivariate proportional hazards regression models were performed to identify significant predictors of DFS and CSS simultaneously. Results: The mean age of the patients diagnosed was 52.43 years (range, 15-95 years), and the median follow-up was 62.71 months (range, 12-92 months). Univariate and multivariate analysis confirmed that NLR ≥2.2 was significantly associated with worse DFS (HR=2.886, 95%CI=1.756-4.745, p<0.001), and same results were obtained in terms of CSS (HR=3.999, 95%CI=2.002-7.987, p<0.001). Similarly, CAR ≥0.07 was independently and significantly associated with poor DFS (HR=3.858, 95%CI=2.346-6.345, p<0.001) and CSS (HR=6.563, 95%CI=3.558-12.106, p<0.001). Conclusion: Preoperative evaluation of NLR and CAR were significant and independent prognostic indicators for luminal breast cancers with HER2-negativity.

Pegylated Liposomal Doxorubicin Versus Epirubicin as Adjuvant Therapy for Stage I-III Breast Cancer.

Background: Conventional anthracyclines, like epirubicin, are cornerstone drugs for breast cancer treatment of all stages, but their cumulative toxicity could cause life-threatening side effects. Pegylated liposomal doxorubicin (PLD), an effective anti-breast cancer drug, has lower toxicity than conventional anthracyclines. This retrospective study compared the efficacy and toxicity profiles between PLD and epirubicin as adjuvant therapy for breast cancer. Patients and Methods: A total of 1,471 patients diagnosed with stage I-III breast cancer between 2000 and 2018 were included in this study, among which 661 were treated with PLD and 810 with epirubicin, with 45.9 months as the median follow-up time. Anti-breast cancer efficacy was assessed with overall survival (OS) and disease-free survival (DFS), while cardiac toxicity was assessed with left ventricular ejection fraction (LVEF) and electrocardiogram (ECG). Results: The Kaplan-Meier method and Cox proportional hazards model revealed that there was no statistical difference in OS or DFS between patients treated with PLD and epirubicin, regardless of cancer stages or molecular subtypes (all p-values > 0.05). In addition, patients had significantly better LEVF and ECG data after adjuvant therapy with PLD (both p-values < 0.05). Conclusion: Based on the large sample size and the long follow-up time of this study, we conclude that PLD has a similar anti-breast cancer efficacy as epirubicin while inducing lower level of cardiac toxicity in Han Chinese. This study suggests that PLD-based adjuvant chemotherapy could be a better option than epirubicin for breast cancer patients especially with existing cardiac disease.

Enhancing the Screening Efficiency of Breast Cancer by Combining Conventional Medical Imaging Examinations With Circulating Tumor Cells.

PURPOSE: Ultrasound (US) and mammogram (MMG) are the two most common breast cancer (BC) screening tools. This study aimed to assess how the combination of circulating tumor cells (CTC) with US and MMG would improve the diagnostic performance. METHODS: CTC detection and imaging examinations, US and MMG, were performed in 238 treatment-naive BC patients, 217 patients with benign breast diseases (BBD), and 20 healthy females. Correlations of CTC, US and MMG with patients' clinicopathological characteristics were evaluated. Diagnostic performances of CTC, US and MMG were estimated by the receiver operating characteristic curves. RESULTS: CTC, US and MMG could all distinguish BC patients from the control (p < 0.0001). Area under curve (AUC) of CTC, US and MMG are 0.855, 0.861 and 0.759, respectively. While US has the highest sensitivity of 0.79, CTC and MMG have the same specificity of 0.92. Notably, CTC has the highest accuracy of 0.83. Combination with CTC increases the AUC of US and MMG to 0.922 and 0.899, respectively. Combining MMG with CTC or US increases the sensitivity of MMG to 0.87, however "CTC + MMG" has a higher specificity of 0.85. "CTC + US" performs the best in BC diagnosis, followed by "CTC + MMG" and then "US + MMG". CONCLUSION: CTC can be used as a diagnostic aid for BC screening. Combination with CTC increases the diagnostic potency of conventional BC screening imaging examinations, US and MMG, in BC diagnosis, especially for MMG.

Evaluation of circulating tumor cells as a prognostic biomarker for early recurrence in stage II-III breast cancer patients using CytoSorter® system: a retrospective study.

PURPOSE: Circulating tumor cells (CTCs) are known to be associated with late recurrence and poor prognosis in breast cancer (BC). Different CTC enrichment platforms have different CTC cut-off values for poor prognosis. This study aimed to evaluate whether preoperative CTCs could be a prognostic factor for early recurrence of disease in BC patients with resectable tumors, and to ascertain the CTC cut-off value for early recurrence with CytoSorter® CTC system. METHODS: Thirty-six stage II and III BC patients who had preoperative (pre-op) CTC detection and underwent a mastectomy or lumpectomy for curative intent between January and May 2018 were enrolled in this retrospective study. CTC detection was performed using CytoSorter® CTC system. Correlations of patients' demographics, clinicopathological characteristics, adjuvant therapies and CTCs with relapse and survival were evaluated. RESULTS: CTCs were detected in 32 out of 36 patients before surgery. Nine patients developed relapses during follow-up, and seven of them were distant recurrence. Univariate analysis showed that CTCs were correlated with two-year recurrence free survival (RFS) and distant RFS (D-RFS) (P = 0.013 and 0.029, respectively). Two-year RFS and D-RFS were 85.2% and 88.9%, respectively, for patients with <4 CTCs, while 44.4% and 55.6%, respectively, for patients with ≧4 CTCs. In multivariate analysis, only CTC was shown to be correlated with two-year RFS (HR: 0.219, 95% CI: [0.058-0.82], P = 0.024) and D-RFS (HR: 0.218, 95% CI [0.048-0.977], P = 0.047). CONCLUSION: BC patients with pre-op CTCs ≥4 per four mL of blood have significantly reduced two-year RFS and D-RFS. A pre-op CTC cut-off of four per four mL of blood was found for CytoSorter® to identify BC patients with a higher risk for early recurrence.

The influence of preoperative biopsy on the surgical method in breast cancer patients: a single-center experience of 3,966 cases in China.

BACKGROUND: The National Surgical Adjuvant Breast and Bowel Project (NSABP) B32 trial reported that the detection rate of sentinel lymph nodes by core needle biopsy (CNB) is higher than that by segmental resection. However, there are few reports regarding the detection rate of sentinel lymph nodes by vacuum-assisted breast biopsy (VABB). Therefore, we analyzed the impact of preoperative biopsy methods on the surgical modes of 3,966 patients with breast cancer in our center. METHODS: In total, 3,966 female breast cancer patients [clinical tumor node metastasis (TNM) stage I-III] were enrolled in this study. Preoperative pathological diagnosis methods included fine needle aspiration (FNA) biopsy, CNB, excision biopsy, and VABB. According to the time of diagnosis. The data were analysis by chi square test, variance analysis and the Kaplan-Meier time series in SPSS 22.0. RESULTS: There was a decrease in the number of patients that underwent excision biopsy (7.3% to 2.7%) and intraoperative freezing (89.4% to 28.9%) over time, while CNB exhibited an increasing trend (1.6% to 55.3%). The positive rates of VABB, CNB, excision biopsy, and FNA were 99.5%, 97.1%, 97.9%, and 82.2%, respectively, and the false negative rates were 0%, 1.8%, 0.34%, and 8.9%, respectively. The overall breast-conserving rate was 36.7%, while the breast-conserving rate for VABB was 57.1%. The axillary sentinel lymph node biopsy rate of cN0 patients was 48.3%, and the intraoperative frozen group (36.7%) and excision biopsy group (39.5%) were lower than the CNB (57.1%) and VABB (77.9%) groups. Until December 2019, there were 350 cases with tumor recurrence or metastasis. The methods of biopsy were not correlated to the cumulative survival time. CONCLUSIONS: Changes to the diagnosis and treatment of breast cancer has a profound impact on the method of tumor biopsy. VABB biopsy offers advantages such as accurate diagnosis, a greater volume of tissue taken at one time, minimally invasive and repeatable, and does not affect the surgical approach and prognosis of patients. It will gradually become the primary method of preoperative pathological evaluation of breast cancer.

A predictive signature for oxaliplatin and 5-fluorouracil based chemotherapy in locally advanced gastric cancer.

Adjuvant chemotherapy(AC) plays a substantial role in the treatment of locally advanced gastric cancer (LAGC), but the response remains poor. We aims to improve its efficacy in LAGC. Therefore, we identified the expression of eight genes closely associated with platinum and fluorouracil metabolism (RRM1, RRM2, RRM2B, POLH, DUT, TYMS, TYMP, MKI67) in the discovery cohort (N=291). And we further validated the findings in TCGA (N=279) and GEO. Overall survival (OS) was used as an endpoint. Univariate and multivariate Cox models were applied. A multivariate Cox regression model was simulated to predict the OS. In the discovery cohort, the univariate Cox model indicated that AC was beneficial to high-RRM1, high-DUT, low-RRM2, low-RRM2B, low-POLH, low-KI67, low-TYMS or low-TYMP patients, the results were validated in the TCGA cohort. The multivariate Cox model showed consistent results. Cumulative analysis indicated that patients with low C-Score respond poorly to the AC, whereas the high and medium C-Score patients significantly benefit from AC. A risk model based on the above variables successfully predicted the OS in both cohorts (AUC=0.75 and 0.67, respectively). Further validation in a panel of gastric cancer cell (GC) lines (N=37) indicated that C-Score is significantly associated with IC50 value to fluorouracil. Mutation profiling showed that C-Score was associated with the number and types of mutations. In conclusion, we successfully simulated a predictive signature for the efficacy of AC in LAGC patients and further explored the potential mechanisms. Our findings could promote precision medicine and improve the prognosis of LAGC patients.

H19/let­7/Lin28 ceRNA network mediates autophagy inhibiting epithelial­mesenchymal transition in breast cancer.

Long non­coding RNA (lncRNA) H19 and Lin28 protein have been shown to participate in various pathophysiological processes, including cellular proliferation, autophagy and epithelial­mesenchymal transition (EMT). A number of studies have investigated lncRNAs, microRNAs and mRNAs, and their roles in the initiation and progression of cancer, in doing so identifying competitive endogenous RNA (ceRNA) networks, including the H19/let­7/Lin28 network. However, whether the H19/let­7/Lin28 ceRNA network is involved in autophagy and EMT in breast cancer (BC) remains unclear. The present study demonstrated that the H19/let­7/Lin28 loop was required for the downregulation of autophagy in BC cells via western blot analysis, reverse transcription­quantitative PCR and autophagy flux monitoring. Using wound healing, migration and invasion assays, and morphological assays, the H19/let­7/Lin28 loop was revealed to promote EMT in BC cells. Moreover, the H19/let­7/Lin28 network was found to contribute to autophagy by inhibiting EMT in BC cells. To the best of our knowledge, the present study is the first to suggest the important roles of the H19/let­7/Lin28 ceRNA network in BC autophagy and EMT, thus providing insight for the use of these molecules as prognostic biomarkers and therapeutic targets in BC metastasis.

Evaluation of the diagnostic value of circulating tumor cells with CytoSorter® CTC capture system in patients with breast cancer.

PURPOSE: In this study, we aimed to investigate the viability of utilizing CytoSorter® system to detect circulating tumor cells (CTCs) and to evaluate the diagnostic value of CTCs in breast cancer (BC). METHODS: A total of 366 females patients suspected of having BC and 30 healthy female volunteers were enrolled in this study. CTCs were enriched by CytoSorter® , a microfluidic-based CTCs capturing platform. CTC detection was performed before operation or biopsy. Based on the biopsy results, patients were divided into two groups, namely patients with BC and patients with benign breast diseases (BBD). Patients with BBD and healthy volunteers were serving as controls. The correlation between CTC enumeration and patients' clinicopathological characteristics was evaluated. The receiver operating characteristic (ROC) curve was plotted to assess the diagnostic potency of CytoSorter® system in BC. RESULTS: Based on the biopsy results, 130 BC patients at different cancer stages and 236 patients with BBD were enrolled in the study. Seven subjects were dropped out from the study. CTCs were detected in 109 of 128 BC patients, in one of 29 healthy volunteers, and in 37 of 232 patients with BBD. Maximum CTC counts detected in BC patients, healthy volunteers, and patients with BBD were 8, 1, and 4, respectively. Statistical analysis showed CTCs could be used to distinguish BC patients from healthy volunteers and patients with BBD (P < .0001). Circulating tumor cells were statistically associated with patients' cancer stage (P = .0126), tumor size (tumor node metastasis [TNM] T stage, P = .0253), cancer type (invasive vs noninvasive, P = .0141), and lymph node metastasis (P = .0436). More CTCs were found in patients at advanced cancer stage or TNM T stage and in patients with invasive tumor or lymph node metastasis. Furthermore, CTC detection rates in BC patients at Tis and T1-4 stages were 50%, 81.67%, 91.07%, 100%, and 100%, respectively. When the CTC cut-off value was set to 2, the ROC curve gave an area under the curve (AUC) of 0.86 with a specificity and sensitivity of 95.4% and 76.56%, respectively. Taken together, CTCs could be used as a diagnostic aid in assistance of cancer screening and staging. CONCLUSION: Circulating tumor cells were successfully isolated in BC patients using CytoSorter® system. CTCs can be used to differentiate BC patients from the patients with BBD or healthy volunteers, and as a diagnostic aid for early cancer diagnosis and cancer staging.

Molecular Characterization and Functional Analysis of Leucine Zipper Transcription Factor Like 1 in Zebrafish (Danio rerio).

Leucine zipper transcription factor like 1 (LZTFL1) is a member of the Bardet-Biedl syndrome gene family. LZTFL1-null mice show the phenotype of obesity, retinal degeneration, and abnormal cilia development. Functionally, LZTFL1 serves as a tumor suppressor and a negative regulator in the hedgehog signaling pathways. The biological function of mammalian LZTFL1 is partially addressed, but data on other model organisms are limited. Zebrafish (Danio rerio) is widely considered as a powerful model to understand the functions of genes implicated in obesity, disease, and cancer. In this study, LZTFL1 homologs were identified in zebrafish (zebrafish LZTFL1). The full-length cDNA of zebrafish LZTFL1 contained 897 bps encoding 298 amino acids. Zebrafish LZTFL1 displayed conserved domains of coil-coil and leucine zipper domain. PCR results showed that zebrafish LZTFL1 was widely distributed in various tissues. Western blot analysis further revealed that zebrafish LZTFL1 was detected to be ectopically expressed in HeLa cells with correct molecular weight. Fluorescence images showed as well that zebrafish LZTFL1 was localized in the cytoplasm. Furthermore, luciferase reporter assay indicated zebrafish LZTFL1 served as a negative regulator in the hedgehog signaling pathway. These data supported that zebrafish was a good model for understanding the biological roles of LZTFL1.

Impact of the 2018 ASCO/CAP HER2 guidelines update for HER2 testing by FISH in breast cancer.

Recently, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the guidelines on HER2 testing for invasive breast cancer. Little is known about the impact of the guidelines update. We aimed to study the impact of the 2018 ASCO/CAP HER2 testing guidelines update. We compared the HER2 FISH results interpreted by 2013 and 2018 ASCO/CAP guidelines in 331 cases of invasive breast cancers. We also analyzed the pathological features and clinical outcomes of these cases. In comparing to the 2013 ASCO/CAP guidelines, the HER2 negative rate was increased significantly from 62.5% to 75.8%(P < 0.05), and 13.3% changed from equivocal to negative by the 2018 guidelines. Our findings indicate that the guidelines update significantly increased the rate of negative results. The reclassification of the equivocal results by the 2018 guidelines is the main reason for this change. Patients with HER2 equivocal results were associated with larger tumor size and higher Ki67 index than those with negative results, while clinical outcomes were similar between them.

KLF4 overcomes tamoxifen resistance by suppressing MAPK signaling pathway and predicts good prognosis in breast cancer.

Tamoxifen resistance represents a daunting challenge to the successful treatment for breast cancer. Krüppel-like factor 4 has critical roles in the development and progression of breast cancer, but its expression, function and regulation in the efficacy of TAM therapy in breast cancer have yet to be investigated. Here, we examined the clinical significance and biologic effects of KLF4 in breast cancer. Firstly, higher expression of KLF4 correlated with increased TAM sensitivity in breast cancer cells, and analysis of GEO datasets indicated that KLF4 expression was positively correlated with ERα and enhanced expression of KLF4 sensitized breast cancer patients to endocrine therapy. Knockdown of KLF4 in MCF-7 and BCAP37 cells led to increased TAM resistance, while ectopic KLF4 expression promoted the responsiveness to TAM in T47D and TAM-resistant MCF-7/TAM cells. Secondly, ectopic KLF4 overexpression suppressed MCF-7/TAM cell growth, invasion and migration. Moreover, KLF4 expression was down-regulated in breast cancer tumor tissues and high expression of KLF4 was associated with favorable outcomes. Mechanistically, KLF4 may enhance the responsiveness of breast cancer cells to TAM through suppressing mitogen-activated protein kinase (MAPK) signaling pathway. We found that ERK and p38 were more activated in MCF-7/TAM compared with MCF-7, and treatment with MAPK-specific inhibitors significantly suppressed cell viability. Knockdown of KLF4 activated ERK and p38 and drove MCF-7 cells to become resistant to TAM. Conversely, overexpression of KLF4 in MCF-7/TAM cells suppressed ERK and p38 signaling and resulted in increased sensitivity to TAM. Therefore, our findings suggested that KLF4 contributed to TAM sensitivity in breast cancer via phosphorylation modification of ERK and p38 signaling. Collectively, this study highlighted the significance of KLF4/MAPK signal interaction in regulating TAM resistance of breast cancer, and suggested that targeting KLF4/MAPK signaling may be a potential therapeutic strategy for breast cancer treatment, especially for the TAM-resistant patients.