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Leptomeningeal metastasis (LM) occurs when tumor cells spread to the leptomeningeal space surrounding the brain and the spinal cord, thereby causing poor clinical outcomes. The triple-negative breast cancer (TNBC) has been associated with symptoms of LM and mechanism remained unclear. Through proteomic analysis, we identified high expression of ICAM2 in leptomeningeal metastatic TNBC cells, which promoted the colonization of the spinal cord and resulted in poor survival in vivo. Two-way demonstration indicated that high levels of ICAM2 promoted blood–cerebrospinal fluid barrier (BCB) adhesion, trans-BCB migration, and stemness abilities and determined the specificity of LM in vivo. Furthermore, pulldown and antibody neutralizing assay revealed that ICAM2 determined the specificity of LM through interactions with ICAM1 in the choroid plexus epithelial cells. Therefore, neutralizing ICAM2 can attenuate the progression of LM and prolong survival in vivo. The results suggested that targeting ICAM2 is a potential therapeutic strategy for LM in TNBC.

Objective To investigate the effects of perturbation-based pinch task training on the sensorimotor performance of the upper extremities of patients with chronic stroke via a novel vibrotactile therapy system. Design A single-blinded randomized controlled trial. Setting A university hospital. Participants Patients with chronic stroke (N=19) randomly assigned into either an experimental group or a control group completed the study. Interventions In addition to 10 minutes of traditional sensorimotor facilitation, each participant in the experimental group received 20 minutes of perturbation-based pinch task training in each treatment session, and the controls received 20 minutes of task-specific motor training twice a week for 6 weeks. Main Outcome Measures The scores for the primary outcome, Semmes-Weinstein monofilament (SWM), and those for the secondary outcomes, Fugl-Meyer Assessment (FMA), amount of use, quality of movement (QOM) on the Motor Activity Log (MAL) scale, and box and block test (BBT), were recorded. All outcome measures were recorded at pretreatment, post treatment, and 12-week follow-up. Results There were statistically significant between-group differences in the training-induced improvements revealed in the SWM results (P=.04) immediately after training and in the BBT results (P=.05) at the 12-week follow-up. The changes in muscle tone and in the QOM, SWM, and BBT scores indicated statistically significant improvements after 12 sessions of treatment for the experimental group. For the control group, a significant statistical improvement was found in the wrist (P Conclusions This study indicated that the perturbation-based pinch task training has beneficial effects on sensory restoration of the affected thumb in patients with chronic stroke.

Brian metastasis, which is diagnosed in 30% of triple-negative breast cancer (TNBC) patients with metastasis, causes poor survival outcomes. Growing evidence has characterized miRNAs involving in breast cancer brain metastasis; however, currently, there is a lack of prognostic plasma-based indicator for brain metastasis. In this study, high level of miR-211 can act as brain metastatic prognostic marker in vivo. High miR-211 drives early and specific brain colonization through enhancing trans-blood–brain barrier (BBB) migration, BBB adherence, and stemness properties of tumor cells and causes poor survival in vivo. SOX11 and NGN2 are the downstream targets of miR-211 and negatively regulate miR-211-mediated TNBC brain metastasis in vitro and in vivo. Most importantly, high miR-211 is correlated with poor survival and brain metastasis in TNBC patients. Our findings suggest that miR-211 may be used as an indicator for TNBC brain metastasis.

Background Maxillary defects after oncologic resection can lead to not only cosmetic deformity but also functional problem. Reconstruction of maxillary defects remains the most challenging endeavor for plastic surgeons. An algorithm to guide plastic surgeons in selecting either the anterolateral thigh flap or the fibula flap for oncologic maxillary reconstruction has not been well established. Methods Patients who underwent oncologic maxillectomy and free flap reconstruction from August 2012 to April 2018 were enrolled for retrospective chart review. Their operative findings and postoperative outcomes were analyzed as a case series. The reconstructive plan was decided using the 4 essential components in sequence: the anterior maxillary arch, orbital floor, eyeball, and oro-sinonasal communication, which are the main considerations in the established classification systems. Accordingly, when the anterior maxillary arch was lost or when the orbital floor was lost with eyeball preservation, a fibula flap was used. Otherwise, an anterolateral thigh flap was used. Results Various maxillectomy defects were successfully reconstructed using an anterolateral thigh flap and a fibula flap. The defect types and corresponding reconstruction were fit into our proposed algorithm and classification. The corresponding outcomes were satisfactory. Conclusion The proposed algorithm by using the anterolateral thigh flap and the fibula flap for oncologic maxillary reconstruction is feasible, simple, and effective.

Purpose Dynamic changes of body image and quality of life (QoL) in breast cancer patients were not commonly investigated. We aimed to compare the dynamic changes in QoL and body image of breast cancer survivors receiving breast-conserving surgery or total mastectomy within 5-10 years after surgery. Methods Patients with non-metastatic breast cancer who received surgery were invited to complete the World Health Organization Quality of Life-Brief (WHOQOL-BREF) questionnaire and the Body Image Scale (BIS) within 10 years after surgery. We applied kernel smoothing methods to capture the dynamic changes of the patients' QoL and body image within 5 years after surgery. We also constructed multiple linear regression models to identify predictive factors for QoL and body image. Results A total of 581 patients were collected, and 211 of them received breast-conserving surgery. There were no statistically significant differences in QoL and body image for breast-conserving surgery versus total mastectomy, but the former showed fluctuating trends. BIS was a predictor of every item and domain in the WHOQOL-BREF in the multiple linear regression model, and explanatory of the trends of dynamic change over time. Patients without lymph node dissection seemed to have less positive feelings but were more satisfied with sexual activities. Conclusion Body image is predictive of the QoL of breast cancer patients. Dynamic changes of body image and QoL would be useful for shared decision-making regarding surgery in breast cancer patients.

Simple Summary SnoRNAs are essential for fundamental cellular processes. However, emerging evidence shows that snoRNAs play regulatory roles during cancer progression. The snoRNA U50A (U50A) is a newly-identified putative tumor suppressor, but its clinical and mechanistic impacts in breast cancer remain elusive. In this study, we quantified the copy number of U50A in breast cancer patient tissues and found that a higher level of U50A expression is correlated with better overall survival in breast cancer patients. By utilizing transcriptomic analysis, we demonstrated that U50A prolongs mitosis and reduces colony-forming ability through downregulating mitosis-related genes. Consistent with these in vitro results, breast cancer tissues expressing higher U50A significantly exhibited accumulated mitotic tumor cells and were associated with reduced tumor size. Altogether, this is the first study showing the clinical, cellular, and regulatory impacts of snoRNA U50A in human breast cancer. Abstract Small nucleolar RNAs (snoRNAs) are small noncoding RNAs generally recognized as housekeeping genes. Genomic analysis has shown that snoRNA U50A (U50A) is a candidate tumor suppressor gene deleted in less than 10% of breast cancer patients. To date, the pathological roles of U50A in cancer, including its clinical significance and its regulatory impact at the molecular level, are not well-defined. Here, we quantified the copy number of U50A in human breast cancer tissues. Our results showed that the U50A expression level is correlated with better prognosis in breast cancer patients. Utilizing RNA-sequencing for transcriptomic analysis, we revealed that U50A downregulates mitosis-related genes leading to arrested cancer cell mitosis and suppressed colony-forming ability. Moreover, in support of the impacts of U50A in prolonging mitosis and inhibiting clonogenic activity, breast cancer tissues with higher U50A expression exhibit accumulated mitotic tumor cells. In conclusion, based on the evidence from U50A-downregulated mitosis-related genes, prolonged mitosis, repressed colony-forming ability, and clinical analyses, we demonstrated molecular insights into the pathological impact of snoRNA U50A in human breast cancer.

BACKGROUND Various kinds of breast reconstruction (BR) options, including implants and autologous, and surgery techniques, including traditional and endoscope assisted, can be used to perform surgery. All options have their own advantages and disadvantages. Women decide on an option depending on the values and preferences they emphasize. Lacking knowledge about BR or having decision difficulties during the treatment decision process makes women experience more decision regret, psychological distress, and poor body image. Delivering decision support with a values clarification exercise using eHealth approaches would be beneficial for patient outcomes. OBJECTIVE This study aims to examine the effects of a decision support app on decision-making quality and psychological morbidity for women considering BR surgery. METHODS This randomized controlled trial included women who were over 20 years of age and were newly diagnosed with breast cancer and candidates for mastectomy. Women having an option for breast conservation were excluded. After being referred from the outpatient physician, the women provided consent and completed the baseline assessment. Women allocated to the control group (CG) received usual care and were provided with a pamphlet with information about types of surgery and the advantages and disadvantages of different surgery types. Women allocated to the intervention group (IG) were given the same pamphlet and guided to use the Pink Journey app to support their decision. Then they were also prompted to discuss the opinions with their significant others. Finally, the decision-making process of using the app was printed out for women that they could take home. Decision conflict, anxiety, and depression were measured at baseline. At 1 week after the intervention (T1) and at 1 month (T2), 8 months (T3), and 12 months (T4) after surgery, the women completed decision conflict, decision regret, anxiety, depression, and body image scales. An intention-to-treat analysis was performed. RESULTS From February 2018 to July 2019, 96 women were randomly assigned to the CG (n=48) or the IG (n=48). Results revealed that body image distress declined significantly for the IG but increased for the CG. The interaction of time and group also reached significance, indicating a significant decrease in body image distress from baseline in the IG compared with the CG after the 12th month (T4) follow-up (β=–2.25, standard error=1.01, P=.027). However, there was no significant difference in decision conflict (P=.21-.87), decision regret (P=.44-.55), anxiety (P=.26-.33), and depression (P=.20-.75), indicating that the decrease in these outcomes in the IG was not greater than those in the CG. CONCLUSIONS Although we found no effect on decision conflict, decision regret, anxiety, and depression, a decision aid that combines surgery information and values clarification can help women reduce their body image distress. CLINICALTRIAL ClinicalTrials.gov NCT04190992; https://clinicaltrials.gov/ct2/show/NCT04190992

Background Sentinel lymph node biopsy (SLNB) is the standard approach for the axillary region in early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes in intraoperative frozen sections (FNSN) using real-world data. Methods A case–control study with a 1:3 ratio was conducted. FNSN was determined when sentinel nodes (SNs) were negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections. Results A total of 20 FNSN cases and 60 matched controls from 333 SLNB patients were enrolled between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between the FNSN and control groups. The FNSN patients had larger tumor sizes on preoperative mammography (P = 0.033) and more lymphatic tumor emboli on core biopsy (P < 0.001). Four FNSN patients had metastasis in nonrelevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in nonrelevant SNs were recognized in two patients. All FNSN patients underwent a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed breast cancer recurrence. The disease-free survival, breast cancer-specific survival, and overall survival in FNSN were not inferior to those in controls. Conclusions Patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, the outcomes of FNSN patients after completing ALND were noninferior to those without SN metastasis. ALND provides a correct staging for patients with metastasis in nonsentinel axillary lymph nodes.

Background: Sentinel lymph node biopsy (SLNB) is the standard approach of the axillary region for early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes of intraoperative frozen section (FNSNs) in real-world data.Methods: A case–control study with a 1:3 ratio was conducted. FNSN was diagnosed when sentinel nodes (SNs) are negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections.Results: A total of 20 FNSN cases and 60 matched controls were enrolled from 333 SLNB patients between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between FNSN and controls. The FNSN patients had larger tumor sizes in preoperative mammography (P = 0.033) and more lymphatic tumor emboli in core biopsy (P < 0.001). Four FNSN patients had metastasis in the non-relevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from the FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in non-relevant SNs were recognized in two patients. All FNSN patients received a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed recurrence of breast cancer. The disease-free survival, disease-specific survival, and overall survival in FNSN were not inferior to the controls.Conclusions: The patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, outcomes of FNSN patients after completing ALND were noninferior to those without metastasis in SNs. ALND provides a correct diagnosis of patients with metastasis in non-sentinel axillary lymph nodes.

In 2016, 12,676 new cases of breast cancer were diagnosed among Taiwan women. In 2018 the standardized death rate of breast cancer was 12.5 per 100,000 persons. Previous studies have integrated data and text mining to yield fusion genes, identify genetic factors for breast cancer and select single-gene feature sets for colon cancer discrimination. However, our study is the first to select significantly different expression between breast normal tissue and cancer using TCGA data and biostatistics, excluding know genes using abstracts from PubMed and natural language processing. The top twenty genes for research potential from the selection of Mining-BreastCancer are EML3, ABCB9, GRASP, KANK3, GPR146, ZNF623, CCDC9, ADCY4, DLL1, ADAM33, GRRP1, LRRN4CL, C14orf180, ABCD4, ABCC6P1, PEAR1, FAM43A, C20orf160, KIF21A and PP-FIA3. Few studies for these genes exist, but they hold significantly different expressions between breast cancer and normal tissue, each pathologic tumor and lymph node, or between each pathologic metastasis. These results show that MiningBreastCancer can help scientists select genes for research potential. MiningBreastCancer is available through http://bio.yungyun.com.tw/MiningBreastCancer.aspx.

Background Sentinel lymph node biopsy (SLNB) is standard approach of axillary region for early breast cancer patients with clinically negative node. The present study investigated patients with false-negative sentinel nodes (FNSN) of intraoperative frozen section.Methods A case-control study with 1:3 ratio was conducted. FNSN was diagnosed as negative sentinel nodes (SNs) in frozen sections, but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) blocks. Control was defined no metastasis of SNs in both frozen and FFPE sections.Results Total 20 FNSN cases and 60 matched-controls were enrolled from 333 SLNB patients between April 1, 2005 and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between FNSN and controls. The FNSN patients had a larger tumor size in preoperative mammography and more lymphatic tumor emboli in core biopsy (P-value 0.033 and

Inflammatory response after peripheral nerve injury is required for clearance of tissue debris and effective regeneration. Studies have revealed that hyaluronic acid (HA) may exert different properties depending on their molecular size. High molecular weight HA (>>1,000 kDa; HMW-HA) displays immunosuppressive properties, whereas low molecular weight HA (

This study examines the influence of partner involvement in decision-making for breast reconstruction (BR) on women’s body image and post-BR decision regret. A cross-sectional and correlational approach was used in a convenience sample of 105 women in Taiwan who had breast cancer (BC) whose partners were involved in decision-making for BR. A structured questionnaire including the Involvement in the Breast Reconstruction Decision-Making Process Scale, the Body Image Scale, and the Decision Regret Scale was administered. Pearson’s r and path analysis were used to examine the relationships among the dyadic BR decision-making process, women’s body image, and decision regret. The greater the amount of medical information women had, the better their body image and the less decision regret they experienced. Moreover, partner involvement was not related to women’s body image, though it was inversely related to women’s decision regret. The final path model showed that the amount of medical information women obtained was directly related to body image and decision regret, while body image also directly influenced decision regret. Overall, the amount of medical information women obtained and their body image explained 45% of the variance in decision regret. Medical teams should provide female BC patients with complete medical information, and through partner involvement, women can be supported to make an appropriate decision regarding BR to achieve optimal levels of body image and lower levels of decision regret.

Background The improved survival rate for breast cancer has increased the number of women living with the diagnosis for more than 5 years. Limited studies have focused on the care needs for long-term healthy survivors of breast cancer. Objective The aims of this study were to understand the care needs of long-term breast cancer survivors and identify related factors that influence these needs. Methods A convenience sampling with a correlational study design was used. Women at least 20 years old, who were given a diagnosis of breast cancer at least 5 years, were recruited from 2 hospital clinics in southern Taiwan. A self-administered questionnaire measuring cancer survivors' unmet needs was administered after obtaining informed consent. Binary logistic regression was used to examine variables associated with unmet care needs. Results Of the 192 women participating, the highest unmet needs related to existential survivorship. The most frequently endorsed unmet need was for an ongoing case manager. Fear of recurrence was associated with 3 aspects including existential survivorship, comprehensive cancer, and quality-of-life unmet needs (odds ratio, 1.14-1.21). Conclusions Even 5 years after the diagnosis and completion of therapy, women continue to report unmet needs. Evaluating women's fear of recurrence to identify high-risk women with unmet needs is critical to providing quality care. Implication for practice Developing appropriate survivorship care programs combined with managing concerns regarding recurrence by a nursing case manager is needed.

We aimed to develop an inexpensive and easy-to-fabricate gelatin-based training phantom for improving the breast biopsy skill and confidence level of residents. Young’s modulus and acoustic properties of the gelatin tissue phantom and simulated tumors were investigated. Six residents were requested to evaluate the effectiveness of the breast phantom. The results showed that 83% (n = 5) of the participants agreed that the ultrasound image quality produced by the breast phantom was excellent or good. Only 17% (n = 1) of the participants claimed that there was room for improvement for the haptic feedback they received during the placement of the core needle into the breast phantom. The mean pre-instructional score was 17% (SD 17%) for all participants. The mean post-instructional score was 83% (SD 17%), giving an overall improvement of 67%. In conclusion, the mean needle biopsy skill and confidence levels of the participants substantially increased through simulation training on our breast phantom. The participants’ feedback showed the phantom is sufficiently realistic in terms of ultrasound imaging and haptic feedback during needle insertion, thus, the training outcome can be linked to the performance of residents when they perform a live biopsy.

Breast cancer is the most common cancer in women, and some patients develop recurrence after standard therapy. Effective predictors are urgently needed to detect recurrence earlier. The activation of Hedgehog signaling in breast cancer is correlated with poor prognosis. PTCH1 is an essential membrane receptor of Hedgehog. However, there are few reports about mutations in Hedgehog genes in breast cancer. We conducted a comprehensive study via an experimental and bioinformatics approach to detect mutated genes in breast cancer. Twenty-two breast cancer patients who developed recurrence within 24 months postoperatively were enrolled with 22 control cancer patients. Targeted deep sequencing was performed to assess the mutations among individuals with breast cancer using a panel of 143 cancer-associated genes. Bioinformatics and public databases were used to predict the protein functions of the mutated genes. Mutations were identified in 44 breast cancer specimens, and the most frequently mutated genes were BRCA2, APC, ATM, BRCA1, NF1, TET2, TSC1, TSC2, NOTCH1, MSH2, PTCH1, TP53, PIK3CA, FBXW7, and RB1. Mutation of these genes was correlated with protein phosphorylation and autophosphorylation, such as peptidyl-tyrosine and protein kinase C phosphorylation. Among these highly mutated genes, mutations of PTCH1 were associated with poor prognosis and increased recurrence of breast cancer, especially mutations in exons 22 and 23. The public sequencing data from the COSMIC database were exploited to predict the functions of the mutations. Our findings suggest that mutation of PTCH1 is correlated with early recurrence of breast cancer patients and will become a powerful predictor for recurrence of breast cancer.

Women with breast cancer have difficulty deciding whether to undergo breast reconstruction when mastectomy is necessary. A computer-based decision aid that can be individualized to provide both surgery information and value clarification may be helpful for women considering breast reconstruction surgery. The objectives of this study are to program a prototype of an application (app) with a value clarification exercise and to evaluate the pilot usability, feasibility, and efficacy of the app. In phase 1, a prototype app called Pink Journey for use on the iPhone OS (IOS) platform was created following the framework of shared decision making. In phase 2, 11 women who were given the option of reconstruction by a breast surgeon were recruited from July 2017 to December 2017. A pretest-posttest design was adopted to test the usability and feasibility of the app. The results showed that the women who used the app reported significantly less decisional conflict after intervention on each subscale of the Decision Conflict scale, i.e., "being informed", "uncertainty", "social support", "effective decision", and "value clarification". This research provides preliminary data indicating that Pink Journey holds promise for decreasing decision conflict. Most women felt that the app was both helpful and user-friendly. The app increased their participation in decision making, helped them obtain more accurate risk perceptions, and clarified their values. It also helped the women make decisions regarding breast reconstruction more confidently.

Fibrosis has been considered as a major cause of capsular contracture. Hypoxia has widely emerged as one of the driving factors for fibrotic diseases. The aim of this study was to examine the association between hypoxia-induced fibrosis and breast capsular contracture formation. Fibrosis, epithelial-mesenchymal transition (EMT), expression levels of hypoxia-inducible factor-1α (HIF-1α), vimentin, fibronectin, and matrix metalloproteinase-9 (MMP-9) in tissues from patients with capsular contracture were determined according to the Baker classification system. Normal breast skin cells in patients with capsular contracture after implant-based breast surgery and NIH3T3 mouse fibroblasts were cultured with cobalt chloride (CoCl2) to mimic hypoxic conditions. Treatment responses were determined by detecting the expression of HIF-1α, vimentin, fibronectin, N-cadherin, snail, twist, occludin, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2, as well as phosphorylated ERK. The expression levels of HIF-1α, vimentin, fibronectin, and fibrosis as well as EMT were positively correlated with the severity of capsular contracture. MMP-9 expression was negatively correlated the Baker score. Hypoxia up-regulated the expression of HIF-1α, vimentin, fibronectin, N-cadherin, snail, twist, TIMP-1 and -2, as well as phosphorylated ERK in normal breast skin cells and NIH3T3. Nonetheless, the expression levels of MMP-9 and occludin were down-regulated in response to CoCl2 treatment. This study is the first to demonstrate the association of hypoxia-induced fibrosis and capsular contracture.

The purpose of this study was to evaluate the effect of a web-based survivorship care plan (SCP) computerized application (APP): (SCP-A) on women's unmet needs, fear of recurrence, symptom distress, anxiety, depression, and quality of life (QoL).Women diagnosed with breast cancer, who had completed their primary treatment but less than 5 years without a sign of recurrence (N = 165) were randomized to a SCP-A or a control group. Self-reported questionnaires were completed by the both groups at baseline (T0), 5 weeks (T1), 3 months (T2), 6 months (T3), and 12 months (T4).Controlling for relevant covariates, mixed effect model analyses revealed a significant decrease in women in the SCP-A group compared to the control group for total unmet needs since T3 (p .004) and fear of recurrence since T4 (p = .02). Women in the SCP-A group also reported significant improvements in QoL at T4 (p .001) relative to those in the control group.Providing SCP using an information website application for women with breast cancer can decrease unmet needs, fear of recurrence, and improve quality of life during short-term and long-term use.Web-based information that provides survivorship care plans for breast cancer survivors are beneficial.

Tamoxifen is the most widely used hormone therapy in estrogen receptor-positive (ER+) breast cancer, which accounts for approximately 70% of all breast cancers. Although patients who receive tamoxifen therapy benefit with respect to an improved overall prognosis, resistance and cancer recurrence still occur and remain important clinical challenges. A recent study identified TAR (HIV-1) RNA binding protein 2 (TARBP2) as an oncogene that promotes breast cancer metastasis. In this study, we showed that TARBP2 is overexpressed in hormone therapy-resistant cells and breast cancer tissues, where it enhances tamoxifen resistance. Tamoxifen-induced TARBP2 expression results in the desensitization of ER+ breast cancer cells. Mechanistically, tamoxifen post-transcriptionally stabilizes TARBP2 protein through the downregulation of Merlin, a TARBP2-interacting protein known to enhance its proteasomal degradation. Tamoxifen-induced TARBP2 further stabilizes SOX2 protein to enhance desensitization of breast cancer cells to tamoxifen, while similar to TARBP2, its induction in cancer cells was also observed in metastatic tumor cells. Our results indicate that the TARBP2-SOX2 pathway is upregulated by tamoxifen-mediated Merlin downregulation, which subsequently induces tamoxifen resistance in ER+ breast cancer.

De Quervain's disease is a stenosing tenosynovitis of the first dorsal compartment of the wrist. Histopathological studies have reported that the thickening of the first dorsal retinaculum is characterized by degeneration rather than inflammation. However, significant infiltration of mast cells and macrophages was noted in a torn tendon study, which suggested that innate immune pathways are part of the mechanism that mediates early tendinopathy. Recently, Interleukin-20 (IL-20) has been reported to provoke potent inflammation and regulate angiogenesis and chemotaxis, which are important for the pathogenesis of inflammatory diseases. The main purpose of our study was to investigate the correlation between IL-20 and tumor necrosis factor (TNF-α) and clarify the potential predictor of tendinopathy progression. Hematoxylin and eosin (H & E) and immunohistochemistry (IHC) staining were used to score and analyze the clinical outcome. TNF-α, IL-20 and related inflammation cytokines were examined. Moreover, the tenocytes were cultured with a stimulator and were used to examine inflammatory cytokine secretions. A real-time polymerase chain reaction (Real-time PCR) was used to detect the gene expression profile. The IHC data showed that TNF-α is up-regulated in grade III de Quervain's. The analysis data showed that IL-20 is positively correlated with TNF-α and disease severity. The real-time PCR showed that the inflammation stimulator enhanced the expression of IL-20 mRNA expression. Inflammation cytokines such as TNF-alpha, transforming growth factor-β (TGF-β) and IL-1 have been used as predictors of de Quervain's; IL-20 is a new predictor based on this study. In the future, IL-20 expression's involvement in the molecular mechanism of the severity of de Quervain's should be further investigated.

Introduction: Breast cancer is the most common cancer in women, and some patients develop recurrence after standard therapy. Effective predictors are urgently needed to detect recurrence earlier. Methods: We conducted a comprehensive study via an experimental and bioinformatics approach to detect mutated genes in breast cancer. Twenty-seven breast cancer patients who developed recurrence within 24 months postoperatively and 22 control cancer patients without recurrence were enrolled from National Cheng Kung University Hospital in Taiwan. Targeted deep sequencing was performed to assess the mutations among individuals with breast cancer using a panel of 143 cancer-associated genes. Bioinformatics and public databases were used to predict the protein functions of the mutated genes. Results: Mutations were identified in 49 breast cancer specimens, and the most frequently mutated genes were BRCA2, TP53, APC, ATM, BRCA1, NOTCH1, TET2, NF1, TSC2, PIK3CA, TSC1, PTEN, MSH2, PTCH1, PIK3R1, STK11, RB1, BAP1, CDH1 and FBXW7. Mutation of these genes was correlated with protein phosphorylation and autophosphorylation. Among these highly mutated genes, mutations of STK11 were associated with poor prognosis and increased recurrence of breast cancer. Knockdown of STK11 in triple negative breast cancer cell lines increases transcription of cytokines and modulates immune response. Conclusion: Our findings suggest that mutation of STK11 is correlated with early recurrence of breast cancer patients and it will become a powerful prognostic marker for recurrence of breast cancer. Suppression of STK11 signaling by gene mutation may contribute to immune escape. Citation Format: Chih-Yang Wang, Yung-Chieh Chang, Yao-Lung Kuo, Kuo-Ting Lee, Pai-Sheng Chen, Chun Hei Antonio Cheung, Che-Hung Shen, Chih-Peng Chang, Ming-Derg Lai, Meng-Ru Shen, Hui-Ping Hsu. Mutation of the STK11 gene predicts recurrence of breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2487.

e15185 Background: Standard treatment for breast cancer patients includes surgery, chemotherapy, radiotherapy, target and endocrine therapy. Immune checkpoint inhibitors are newly developing medications. The theoretical basis of immunotherapy is the interaction between cancer cells and tumor-infiltrating immune cells. Cancer cells secrete cytokines and create a specific tumor immune microenvironment (TIME) to attract or modulate immune cells. Further, genetic mutations or copy-number variations in cancer cells contribute to immunosuppression. Liver kinase B1 (LKB1) protein ( STK11 gene) is the upstream of AMP activated Protein Kinase (AMPK)/mammalian Target of Rapamycin Complex 1 (mTORC1) signaling pathway. STK11/LKB1 is one of the possible pathways modulating TIME. Methods: Twenty-seven breast cancer patients who developed recurrence within postoperative 24 months and 22 control cancer patients without recurrence were enrolled from National Cheng Kung University Hospital in Taiwan. Targeted deep sequencing was performed to assess the mutations among individuals with breast cancer using a panel of 143 cancer-associated genes. Bioinformatics and public databases were used to predict the protein functions of the STK11 genes. Immunohistochemical staining of LKB1 protein was performed in clinical specimens. Immune-related molecules were analyzed by RNA sequencing and cytokine array after suppression of STK11. Results: Mutations of STK11 gene were detected in recurrent patients and associated with poor prognosis of patients. From immunohistochemical study, the patients with low LKB1 expression had a worse survival. We utilized CRISPER/Cas9 system to transfect sgRNA into three mouse cell lines, including M158, NF639 and PY8119. RNA sequencing was performed in parental and Stk11-sgRNA cells. Immune-related pathways were ranked in the top 10 networks. Increased mRNA expression of Csf3 (protein G-CSF), Cxcl5, and Ccl2 was detected. The results are confirmed by cytokine array. The expression of G-CSF (gene Csf3) and CXCL5 (gene Cxcl5) proteins was increased in Stk11-sgRNA cells. The results were similar with RNA sequencing. Conclusions: Our findings suggest that suppression of STK11/LKB1 is correlated with early recurrence of breast cancer patients and contributes to modulate TIME. The STK11/LKB1 and downstream AMPK/mTORC1 pathways may be potential targets for immunotherapy.