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Introduction: Post-mastectomy radiation therapy is an important component of adjuvant therapy for high-risk patients. However, radiation to reconstructed breasts can cause various complications. Recently, hypofractionated (HF) protocols have been adopted in several countries. Here, we aimed to assess the impact of HF protocols on implant-reconstructed breasts through a meta-analysis and systematic review of the currently available literature., Methods: Records published until August 2023 were systematically searched in PubMed, Cochrane Library, and EMBASE databases. Keywords included hypofractionation radiotherapy, mastectomy, and breast reconstruction. Studies that utilized HF and conventional fractionation (CF) after prosthetic reconstruction were selected. Due to the rarity of events in outcomes, Mantel-Haenszel's odds ratios were calculated using a fixed-effect model to compare the complication rates between HF and CF groups. For analysis with high heterogeneity, a random effect model was used., Results: Seven articles with 924 implant reconstructions, in which 506 (54.8 %) underwent HF were included. HF patients received 43.8 Gy on average, while CF patients received 51.2 Gy. Mean follow-up ranged from 10.6 to 35 months. Seven studies were included in the meta-analysis. HF groups had a significantly lower risk of capsular contracture (OR 0.25, 95 % CI 0.11-0.55), major revision surgery (OR 0.19, 95 % CI 0.05-0.80), and wound dehiscence (OR 0.24, 95 % CI 0.07-0.78) compared to CF groups. The risks of other complications were not statistically significant., Conclusion: This study indicates that HF protocols are associated with fewer complications than CF protocols in implant-reconstructed patients. These findings suggest that the application of HF PMRT in implant-reconstructed patients with breast cancer is plausible., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The surface-enhanced Raman scattering (SERS) technique has garnered significant interest due to its ultrahigh sensitivity, making it suitable for addressing the growing demand for disease diagnosis. In addition to its sensitivity and uniformity, an ideal SERS platform should possess characteristics such as simplicity in manufacturing and low analyte consumption, enabling practical applications in complex diagnoses including cancer. Furthermore, the integration of machine learning algorithms with SERS can enhance the practical usability of sensing devices by effectively classifying the subtle vibrational fingerprints produced by molecules such as those found in human blood. In this study, we demonstrate an approach for early detection of breast cancer using a bottom-up strategy to construct a flexible and simple three-dimensional (3D) plasmonic cluster SERS platform integrated with a deep learning algorithm. With these advantages of the 3D plasmonic cluster, we demonstrate that the 3D plasmonic cluster (3D-PC) exhibits a significantly enhanced Raman intensity through detection limit down to 10 -6 M (femtomole-(10 -17 mol)) for p -nitrophenol (PNP) molecules. Afterward, the plasma of cancer subjects and healthy subjects was used to fabricate the bioink to build 3D-PC structures. The collected SERS successfully classified into two clusters of cancer subjects and healthy subjects with high accuracy of up to 93%. These results highlight the potential of the 3D plasmonic cluster SERS platform for early breast cancer detection and open promising avenues for future research in this field.

Background: Implant-based breast reconstruction has evolved over time. However, the effects of prepectoral breast reconstruction (PBR) compared with those of subpectoral breast reconstruction (SBR) have not been clearly defined. Therefore, this study aimed to compare the occurrence of surgical complications between PBR and SBR to determine the procedure that is effective and relatively safe., Methods: The PubMed, Cochrane Library, and EMBASE databases were searched for studies published until April of 2021 comparing PBR and SBR following mastectomy. Two authors independently assessed the risk of bias. General information on the studies and surgical outcomes were extracted. Among 857 studies, 34 and 29 were included in the systematic review and meta-analysis, respectively. Subgroup analysis was performed to clearly compare the results of patients who underwent postmastectomy radiation therapy., Results: Pooled results showed that prevention of capsular contracture (OR, 0.57; 95% CI, 0.41 to 0.79) and infection control (OR, 0.73; 95% CI, 0.58 to 0.92) were better with PBR than with SBR. Rates of hematoma, implant loss, seroma, skin-flap necrosis, and wound dehiscence were not significantly different between PBR and SBR. PBR considerably improved postoperative pain, BREAST-Q score, and upper arm function compared with SBR. Among postmastectomy radiation therapy patients, the incidence rates of capsular contracture were significantly lower in the PBR group than in the SBR group (OR, 0.14; 95% CI, 0.05 to 0.35)., Conclusions: The results showed that PBR had fewer postoperative complications than SBR. The authors' meta-analysis suggests that PBR could be used as an alternative technique for breast reconstruction in appropriate patients., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: We investigated the effects of sevoflurane exposure on the expression of matrix metalloproteinase (MMP), expression and ablation of natural killer group 2, member D (NKG2D) ligands (UL16-binding proteins 1-3 and major histocompatibility complex class I chain-related molecules A/B), and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells., Methods: Three human breast cancer cell lines (MCF-7, MDA-MB-453, and HCC-70) were incubated with 0 (control), 600 (S6), or 1200 μM (S12) sevoflurane for 4 h. The gene expression of NKG2D ligands and their protein expression on cancer cell surfaces were measured using multiplex polymerase chain reaction (PCR) and flow cytometry, respectively. Protein expression of MMP-1 and -2 and the concentration of soluble NKG2D ligands were analyzed using western blotting and enzyme-linked immunosorbent assays, respectively., Results: Sevoflurane downregulated the mRNA and protein expression of the NKG2D ligand in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells but did not affect the expression of MMP-1 or -2 or the concentration of soluble NKG2D ligands in the MCF-7, MDA-MB-453, and HCC-70 cells. Sevoflurane attenuated NK cell-mediated cancer cell lysis in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells (P = 0.040, P = 0.040, and P = 0.040, respectively)., Conclusions: Our results demonstrate that sevoflurane exposure attenuates NK cell-mediated cytotoxicity in breast cancer cells in a dose-dependent manner. This could be attributed to a sevoflurane-induced decrease in the transcription of NKG2D ligands rather than sevoflurane-induced changes in MMP expression and their proteolytic activity.

Objective: This systematic review and meta-analysis evaluated the accuracy of preoperative breast magnetic resonance imaging (MRI) features and tumor-to-nipple distance (TND) for diagnosing occult nipple-areolar complex (NAC) involvement in breast cancer., Materials and Methods: The MEDLINE, Embase, and Cochrane databases were searched for articles published until March 20, 2022, excluding studies of patients with clinically evident NAC involvement or those treated with neoadjuvant chemotherapy. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Two reviewers independently evaluated studies that reported the diagnostic performance of MRI imaging features such as continuity to the NAC, unilateral NAC enhancement, non-mass enhancement (NME) type, mass size (> 20 mm), and TND. Summary estimates of the sensitivity and specificity curves and the summary receiver operating characteristic (SROC) curve of the MRI features for NAC involvement were calculated using random-effects models. We also calculated the TND cutoffs required to achieve predetermined specificity values., Results: Fifteen studies (n = 4002 breast lesions) were analyzed. The pooled sensitivity and specificity (with 95% confidence intervals) for NAC involvement diagnosis were 71% (58-81) and 94% (91-96), respectively, for continuity to the NAC; 58% (45-70) and 97% (95-99), respectively, for unilateral NAC enhancement; 55% (46-64) and 83% (75-88), respectively, for NME type; and 88% (68-96) and 58% (40-75), respectively, for mass size (> 20 mm). TND had an area under the SROC curve of 0.799 for NAC involvement. A TND of 11.5 mm achieved a predetermined specificity of 85% with a sensitivity of 64%, and a TND of 12.3 mm yielded a predetermined specificity of 83% with a sensitivity of 65%., Conclusion: Continuity to the NAC and unilateral NAC enhancement may help predict occult NAC involvement in breast cancer. To achieve the desired diagnostic performance with TND, a suitable cutoff value should be considered., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Society of Radiology.)

Background: Breast cancer brain metastasis (BCBM) is a growing therapeutic challenge and clinical concern. Stromal cancer-associated fibroblasts (CAFs) are crucial factors in the modulation of tumorigeneses and metastases. Herein, we investigated the relationship between the expression of stromal CAF markers in metastatic sites, platelet-derived growth factor receptor-beta (PDGFR-β), and alpha-smooth muscle actin (α-SMA) and the clinical and prognostic variables in BCBM patients., Methods: Immunohistochemistry (IHC) of the stromal expression of PDGFR-β and α-SMA was performed on 50 cases of surgically resected BCBM. The expression of the CAF markers was analyzed in the context of clinico-pathological characteristics., Results: Expression of PDGFR-β and α-SMA was lower in the triple-negative (TN) subtype than in other molecular subtypes (p = 0.073 and p = 0.016, respectively). And their expressions were related to a specific pattern of CAF distribution (PDGFR-β, p = 0.009; α-SMA, p = 0.043) and BM solidity (p = 0.009 and p = 0.002, respectively). High PDGFR-β expression was significantly related to longer recurrence-free survival (RFS) (p = 0.011). TN molecular subtype and PDGFR-β expression were independent prognostic factors of recurrence-free survival (p = 0.029 and p = 0.030, respectively) and TN molecular subtype was an independent prognostic factor of overall survival (p < 0.001)., Conclusions: Expression of PDGFR-β in the stroma of BM was associated with RFS in BCBM patients, and the clinical implication was uniquely linked to the low expression of PDGFR-β and α-SMA in the aggressive form of the TN subtype., (© 2023. The Author(s).)

Purpose: To analyze BE on ABUS using BI-RADS and a modified classification in association with mammographic density and clinical features., Methods: Menopausal status, parity, and family history of breast cancer were collected for 496 women who underwent ABUS and mammography. Three radiologists independently reviewed all ABUS BE and mammographic density. Statistical analyses including kappa statistics (κ) for interobserver agreement, Fisher's exact test, and univariate and multivariate multinomial logistic regression were performed., Results: BE distribution between the two classifications and between each classification and mammographic density were associated (P < 0.001). BI-RADS homogeneous-fibroglandular (76.8%) and modified heterogeneous BE (71.3%, 75.7%, and 87.5% of mild, moderate, and marked heterogeneous background echotexture, respectively) tended to be dense. BE was correlated between BI-RADS homogeneous-fat and modified homogeneous background (95.1%) and between BI-RADS homogeneous-fibroglandular or heterogeneous (90.6%) and modified heterogeneous (86.9%) (P < 0.001). In multinomial logistic regression, age < 50 years was independently associated with heterogeneous BE (OR, 8.89, P = 0.003, in BI-RADS; OR, 3.74; P = 0.020 in modified classification)., Conclusion: BI-RADS homogeneous-fat and modified homogeneous BE on ABUS was likely to be mammographically fatty. However, BI-RADS homogeneous-fibroglandular or heterogeneous BE might be classified as any modified BE. Younger age was independently associated with heterogeneous BE., (© 2023 Wiley Periodicals LLC.)

Multi-color flow cytometry is the standard approach for immunophenotyping clinical samples. With the recent advances in cancer immunotherapy, myeloid-derived suppressor cells (MDSC), immature myeloid-lineage cells in cancer patient blood and the tumor microenvironment, are highlighted as an important immune cell population that correlates with prognosis and therapeutic efficacy. In contrast to their clear functions and existence, immunophenotyping of MDSC is not consistent among investigators due to surface antigens overlapping with many normal hematopoietic lineage cell populations. We performed a clinical study and analyzed more than 1000 breast cancer patients blood samples to quantitate MDSC during breast cancer progression. In this methodology manuscript, we described detailed procedures for study design, sample logistics and handling, staining and flow cytometric analysis. This protocol used a 7-color fluorochrome-conjugated antibody panel to analyze polymorphonuclear (PMN)- and monocytic (M)-MDSC subsets simultaneously. The interim analysis results of this study showed that both PMN and M-MDSC populations are increased in patients with bone metastasis compared with patients with visceral organ metastasis. In conclusion, this work provides a versatile, comprehensive, and practical protocol to measure MDSC in patient blood samples., Competing Interests: Declaration of Competing Interest All authors declare no financial conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Using a parallel-process latent growth model (LGM), this study examined whether posttraumatic stress symptoms (PTSS) are associated with the trajectory of sleep disturbance (SD) and fatigue and whether the SD trajectory mediates the PTSS-fatigue relationship., Methods: Data were from 215 patients with breast cancer recruited from a tertiary hospital in South Korea. A self-report survey was administered at four time points during the course of adjuvant chemotherapy., Results: The mean age of the participants was 46.69 (SD = 9.08) and the majority was at stage I and the average months since diagnosis was 1.33 (SD = 1.43). Unconditional parallel-process LGM indicated that SD and fatigue were positively associated with each other, both in terms of initial status and growth rate. Then, the conditional parallel-process LGM with baseline PTSS (i.e., avoidance, intrusion, and hyperarousal) as predictors were examined and anxiety, depressive symptoms and chronotype were entered as covariates in the model. Results indicated that a higher initial status and faster growth of SD were associated with a faster increase in fatigue. Greater baseline hyperarousal was directly related to a higher initial status and a slower increase in SD, and higher initial fatigue. Furthermore, a higher hyperarousal was associated with a greater initial SD, which was related to a faster increase in fatigue. Additionally, the late chronotype was related to a faster increase in fatigue through its impact on the initial SD., Conclusions: The detrimental impact of hyperarousal on the SD trajectory and fatigue suggests the need to intervene in PTSS and SD early and throughout the course of cancer treatments to prevent fatigue., (© 2022 John Wiley & Sons Ltd.)

Backgrounds: In this study, we evaluated the incidence and outcomes of pregnancy after breast cancer was diagnosed in women of childbearing age. Additionally, we evaluated the prognosis of patients who became pregnant after breast cancer, according to the treatment., Methods: This was a retrospective cohort study of women aged 20-45 years who were surgically treated for breast cancer between 2004 and 2014 using the Korean National Health Insurance database. The patients were classified into six groups according to the treatment. Propensity score matching was applied to the cohort to analyze the risk of breast cancer-associated mortality after pregnancy and childbirth., Results: Of the 45,765 patients who had been newly diagnosed with breast cancer, 1826 (4%) became pregnant after breast cancer diagnosis. Among the pregnant group, the HR of the risk of death was 0.15 (95% CI, 0.06 to 0.36) for patients who became pregnant ≥49 months after the diagnosis. In patients who received endocrine therapy and chemotherapy, the pregnant group had better prognosis than the non-pregnant group. There was no significant difference between the pregnant group and the non-pregnant group in patients who received chemotherapy and trastuzumab with or without endocrine therapy., Conclusion: The risk of death was low in women who became pregnant ≥49 months after the diagnosis of breast cancer. The prognosis of pregnant women was non-inferior to that of non-pregnant women, even in women who received trastuzumab. These findings provide reassurance to patients with HER2-positive cancer who are considering future pregnancy., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Patients with breast cancer receiving neoadjuvant chemotherapy are at increased risk of poor health-related quality of life (HRQOL). This study examined clinical caseness on depression and anxiety mediate the relationship between resilience and HRQOL in patients with breast cancer., Methods: A total of 193 patients with breast cancer undergoing neoadjuvant chemotherapy completed questionnaires including the Connor-Davidson Resilience Scale, Hospital Anxiety and Depression Scale (HADS), and Functional Assessment of Cancer Therapy-Breast before the first session (T0), before the start of the last session (T1), and 6 months after the end (T2) of chemotherapy. Mediation analyses using a bootstrapping method was performed., Results: The indirect effect (IE) through T1 depression was significant (IE through depression = 0.043, 95% confidence interval [CI] [0.002-0.090]), while IE through T1 anxiety was not significant (IE through anxiety = 0.037, 95% CI [-0.010-0.097]) in the association between T0 resilience and T2 HRQOL., Conclusions: Clinical caseness on HADS depression subscale during chemotherapy was a mediating factor of the relationship between resilience before chemotherapy and HRQOL after chemotherapy in patients with breast cancer receiving neoadjuvant chemotherapy. Depression during chemotherapy in patients with breast cancer may be a target symptom of screening and intervention to maintain the HRQOL after chemotherapy. Also, patients with low resilience are more likely to develop depression during chemotherapy, and clinicians should carefully monitor whether depression occurs in these patients with low resilience., (© 2021 John Wiley & Sons Ltd.)

Purpose: Fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT) affects the management of patients with breast cancer. Our study aimed to determine the predictive ability of characteristics such as lymph node involvement or subtype and the prognostic value of pretreatment FDG-PET/CT in breast cancer., Method: A total of 270 patients who were confirmed with breast cancer histopathologically and underwent pretreatment FDG-PET/CT were enrolled in the study. Nuclear medicine specialists obtained the readings and measured the maximum standardized uptake value (SUVmax) of the images. Tumor and lymph node SUVmax were evaluated according to lymph node metastasis and subtype status. Survival outcomes were analyzed by the Kaplan-Meier method., Results: The lymph node SUVmax and the lymph node/tumor SUVmax ratio were significantly higher in the subgroup of patients with lymph node metastasis than in those without lymph node metastasis. High cutoff lymph node SUVmax value and lymph node/tumor SUVmax ratio were confirmed as significant predictive factors in multivariate analysis. In a comparison of the tumor SUVmax values, the more biological aggressive subtype showed higher tumor SUVmax values. In survival analysis, tumor SUVmax and lymph node SUVmax were significant predisposing factors for disease-free survival in breast cancer. In subgroup analysis, tumor SUVmax was a more significant prognostic factor in patients who had breast cancer with tumor sizes of ≤2 cm. The lymph node SUVmax was more a significant prognostic factor in patients who had breast cancer with lymph node metastasis., Conclusion: In this study, we showed that the SUVmax of FDG-PET/CT was a useful predictor of lymph node metastasis and breast cancer prognosis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Schwannoma in the breast parenchyma is very unusual. It usually develops on the head, neck, and extensor surfaces of the upper and lower extremities., Patient Concerns: We report a case of a 60-year-old woman with a palpable and painful mass. Clinically, she experienced neuropathic pain at the mass site., Diagnoses: The tumor was a 1 cm, well-circumscribed mass, and revealed schwannoma on core needle biopsy., Interventions: The patient underwent wide excision., Outcomes: No postoperative complications were observed. A six-month follow-up revealed no recurrence., Lessons Subsections: Although breast schwannoma is a very rare tumor, it is a very important consideration in case of a Breast Imaging-Report and Data System 4A lesion with a painful and palpable mass., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer., (© 2021. The Author(s).)

Breast cancer is one of the major causes of deaths due to cancer, especially in women. The crucial barrier for breast cancer treatment is resistance to radiation therapy, one of the important local regional therapies. We previously established and characterized radio-resistant MDA-MB-231 breast cancer cells (RT-R-MDA-MB-231 cells) that harbor a high expression of cancer stem cells (CSCs) and the EMT phenotype. In this study, we performed antibody array analysis to identify the hub signaling mechanism for the radiation resistance of RT-R-MDA-MB-231 cells by comparing parental MDA-MB-231 (p-MDA-MB-231) and RT-R-MDA-MB-231 cells. Antibody array analysis unveiled that the MAPK1 protein was the most upregulated protein in RT-R-MDA-MB-231 cells compared to in p-MDA-MB-231 cells. The pathway enrichment analysis also revealed the presence of MAPK1 in almost all enriched pathways. Thus, we used an MEK/ERK inhibitor, PD98059, to block the MEK/ERK pathway and to identify the role of MAPK1 in the radio-resistance of RT-R-MDA-MB-231 cells. MEK/ERK inhibition induced cell death in both p-MDA-MB-231 and RT-R-MDA-MB-231 cells, but the death mechanism for each cell was different; p-MDA-MB-231 cells underwent apoptosis, showing cell shrinkage and PARP-1 cleavage, while RT-R-MDA-MB-231 cells underwent necroptosis, showing mitochondrial dissipation, nuclear swelling, and an increase in the expressions of CypA and AIF. In addition, MEK/ERK inhibition reversed the radio-resistance of RT-R-MDA-MB-231 cells and suppressed the increased expression of CSC markers (CD44 and OCT3/4) and the EMT phenotype (β-catenin and N-cadherin/E-cadherin). Taken together, this study suggests that activated ERK signaling is one of the major hub signals related to the radio-resistance of MDA-MB-231 breast cancer cells.

Abstract: This study evaluated the outcomes and prognostic factors for breast cancer according to initial lymph node (LN) status. Among patients with LN-negative breast cancer, we also focused on the prognostic value of estrogen receptor (ER) status.Medical records were retrospectively reviewed for 715 patients who underwent curative surgery for breast cancer between January 2005 and December 2015 at a single Korean institution. We evaluated factors that were associated with metastasis-free survival (MFS) according to LN status.Among the 715 patients (age: 28-87 years), 458 patients (64.1%) did not have axillary LN metastasis. Relative to patients without LN metastasis, patients with LN metastasis had larger tumor sizes and higher histological grades. Among patients with no LN metastasis, ER positivity was associated with non-significantly poorer MFS than ER negativity (mean survival: 138.90 months vs. 146.99 months, p = .17), and patients with LN-negative ER-positive disease had MFS rates of 91.7% at 5 years and 74.5% at 10 years. Among patients with LN-negative ER-positive disease, a poor prognosis was significantly associated with larger tumor size (≥2 cm, P = .03) and older age (≥50 years, P = .03).These results indicate that the risk of metastasis increases over time for patients with LN-negative ER-positive breast cancer, and especially for older patients or patients with larger tumors., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Complications of breast cancer treatment can cause physical and psychosocial distress in patients. Yoga demonstrates substantial potential as a supportive therapy for patients with breast cancer. Our aim is to conduct a meta-analysis of randomized controlled trials to evaluate the effectiveness of yoga in enhancing the quality of life (QoL) of patients with breast cancer., Methods: We searched for studies published before March 2020 in the PubMed, Embase, and Cochrane Library databases. Individual effect sizes were standardized, and the pooled effect size was calculated using a random effect model. Measured outcomes included QoL, anxiety and depression, stress, fatigue, pain severity, and sleep quality., Results: In total, 26 trials involving 2069 patients were reviewed. Significant enhancement in QoL was observed immediately after the yoga intervention. The pooled mean differences in social (weighted mean difference [WMD]: 1.36, 95% confidence interval [CI] 0.12-2.61), emotional (WMD: 1.46, 95% CI 0.26-2.66), and functional well-being (WMD: 2.04, 95% CI 0.21-3.87) were significantly higher in the yoga group than in the control group. Patients practicing yoga exhibited significant improvements in physical well-being, mental well-being, and sleep quality as well as reductions in anxiety, depression, stress, fatigue, and pain severity after the intervention., Conclusions: Yoga may enhance QoL in patients with breast cancer experiencing post-treatment complications. Therefore, we recommend yoga as a supportive therapy for patients with breast cancer to relieve post-treatment distress.

Background: We aimed to identify whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are more useful predictors after initial intention to treat than at the time of diagnosis., Methods: We collected the medical data of 533 patients. The results of the peripheral blood sampling before the primary treatments were labeled as initial cohort, and those obtained between 24 and 36 months after initial treatment were defined as the 2nd cohort. Delayed metastasis has been defined as distant metastasis 2 years after treatment, and survival outcome was estimated and compared across groups., Results: Median follow-up duration was 74 months (24-162 months), and 53 patients experienced delayed metastasis. In univariate analysis, metastasis-free survival, patient age at diagnosis, tumor size, axillary lymph node metastasis, HER-2 status, initial NLR and PLR, and 2nd NLR and PLR were found to be significantly associated with delayed metastasis. However, in multivariate analysis, only the 2nd NLR and PLR were found to be significantly associated with delayed metastasis, excluding initial NLR and PLR. Metastasis-free survival was analyzed through the pattern changes of NLR or PLR. The results revealed that patients with continued low NLR and PLR values at pre- and post-treatment (low initial values and 2nd values) showed a significantly better prognosis than those with a change in value or continued high NLR and PLR., Conclusions: We identified that patients with persistent high NLR and PLR after initial treatment have significant worse prognosis in terms of late metastasis. Therefore, these results suggest that NLR and PLR are more useful in predicting prognosis post-treatment.

Objective: This study examined the growth trajectory of fear of cancer recurrence (FCR) and its predictors, and the association of that trajectory with the beliefs and rates of medication adherence in patients with breast cancer., Methods: Two hundred and ten patients with breast cancer undergoing adjuvant endocrine therapy in a university hospital in Seoul, Korea, were followed up five times over 18 months following surgery, and data from the final 162 patients were analyzed., Results: Latent class growth analysis identified three classes. Classes 1 (38.31%) and 2 (39.89%) showed low and moderate FCR levels, respectively, with a decreasing trend over time. Class 3 (21.80%) showed a high FCR level with an initially decreasing but increasing trend afterward s. Lower education and unemployed status were associated with the high FCR class. Higher depression was more associated with the moderate FCR class than the low FCR class. Higher emotional representation was more associated with the high FCR class than with low FCR class, and greater illness comprehension was more associated with the moderate FCR class than with the high FCR class. Both necessity and concerns about medication were the highest in the high FCR class. However, self-reported medication adherence rates did not significantly differ between the classes., Conclusions: A high level of FCR appears to persist over time, and given its association with greater concerns about medication, monitoring and management of FCR throughout the cancer trajectory., (© 2020 John Wiley & Sons Ltd.)

Objective: To investigate the clinical feasibility of synthetic diffusion-weighted imaging (sDWI) at different b-values in patients with breast cancer by assessing the diagnostic image quality and the quantitative measurements compared with conventional diffusion-weighted imaging (cDWI)., Materials and Methods: Fifty patients with breast cancer were assessed using cDWI at b-values of 800 and 1500 s/mm² (cDWI 800 and cDWI 1500 ) and sDWI at b-values of 1000 and 1500 s/mm² (sDWI 1000 and sDWI 1500 ). Qualitative analysis (normal glandular tissue suppression, overall image quality, and lesion conspicuity) was performed using a 4-point Likert-scale for all DWI sets and the cancer detection rate (CDR) was calculated. We also evaluated cancer-to-parenchyma contrast ratios for each DWI set in 45 patients with the lesion identified on any of the DWI sets. Statistical comparisons were performed using Friedman test, one-way analysis of variance, and Cochran's Q test., Results: All parameters of qualitative analysis, cancer-to-parenchyma contrast ratios, and CDR increased with increasing b-values, regardless of the type of imaging (synthetic or conventional) ( p < 0.001). Additionally, sDWI 1500 provided better lesion conspicuity than cDWI 1500 (3.52 ± 0.92 vs. 3.39 ± 0.90, p < 0.05). Although cDWI 1500 showed better normal glandular tissue suppression and overall image quality than sDWI 1500 (3.66 ± 0.78 and 3.73 ± 0.62 vs. 3.32 ± 0.90 and 3.35 ± 0.81, respectively; p < 0.05), there was no significant difference in their CDR (90.0%). Cancer-to-parenchyma contrast ratios were greater in sDWI 1500 than in cDWI 1500 (0.63 ± 0.17 vs. 0.55 ± 0.18, p < 0.001)., Conclusion: sDWI 1500 can be feasible for evaluating breast cancers in clinical practice. It provides higher tumor conspicuity, better cancer-to-parenchyma contrast ratio, and comparable CDR when compared with cDWI 1500 ., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2020 The Korean Society of Radiology.)

Anthocyanins isolated from Vitis coignetiae Pulliat (Meoru in Korea) (AIMs) have various anti-cancer properties by inhibiting Akt and NF-κB which are involved in drug resistance. Cisplatin (CDDP) is one of the popular anti-cancer agents. Studies reported that MCF-7 human breast cancer cells have high resistance to CDDP compared to other breast cancer cell lines. In this study, we confirmed CDDP resistance of MCF-7 cells and tested whether AIMs can overcome CDDP resistance of MCF-7 cells. Cell viability assay revealed that MCF-7 cells were more resistant to CDDP treatment than MDA-MB-231 breast cancer cells exhibiting aggressive and high cancer stem cell phenotype. AIMs significantly augmented the efficacy of CDDP with synergistic effects on MCF-7 cells. Molecularly, Western blot analysis revealed that CDDP strongly increased Akt and moderately reduced p-NF-κB and p-IκB and that AIMs inhibited CDDP-induced Akt activation, and augmented CDDP-induced reduction of p-NF-κB and p-IκB in MCF-7 cells. In addition, AIMs significantly downregulated an anti-apoptotic protein, XIAP, and augmented PARP-1 cleavage in CDDP-treated MCF-7 cells. Moreover, under TNF-α treatment, AIMs augmented CDDP efficacy with inhibition of NF-κB activation on MCF-7 cells. In conclusion, AIMs enhanced CDDP sensitivity by inhibiting Akt and NF-κB activity of MCF-7 cells that show relative intrinsic CDDP resistance.

Vitis coignetiae Pulliat (Meoru in Korea) has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. Evidence suggests that NF-κB activation is mainly involved in cancer cell proliferation, invasion, angiogenesis, and metastasis. TNF-α also enhances the inflammatory process in tumor development. Recently, flavonoids from plants have been reported to have inhibitory effects on NF-κB activities. We investigated the effects of anthocyanins extracted from the fruits of Vitis coignetiae Pulliat (AIM, anthocyanins isolated from Meoru (AIM)) on TNF-α-induced NF-κB activities in MCF-7 human breast cancer cells and the molecules involved in AIM-induced anti-cancer effects, especially on cancer metastasis. We performed cell viability assay, gelatin zymography, invasion assay, and western blot analysis to unravel the anti-NF-κB activity of AIMs on MCF-7 cells. AIM suppressed the TNF-α effects on the NF-κB-regulated proteins involved in cancer cell proliferation (COX-2, C-myc), invasion, and angiogenesis (MMP-2, MMP9, ICAM-1, and VEGF). AIM also increased the expression of E-cadherin, which is one of the hallmarks of the epithelial-mesenchymal transition (EMT) process. In conclusion, this study demonstrates that the anthocyanins isolated from the fruits of Vitis coignetiae Pulliat acts as an inhibitor of TNF-α induced NF-κB activation, and subsequent downstream molecules involved in cancer proliferation, invasion, adhesion, angiogenesis, and thus have anti-metastatic activities in MCF-7 breast cancer cells.

To assist radiologists in breast cancer classification in automated breast ultrasound (ABUS) imaging, we propose a computer-aided diagnosis based on a convolutional neural network (CNN) that classifies breast lesions as benign and malignant. The proposed CNN adopts a modified Inception-v3 architecture to provide efficient feature extraction in ABUS imaging. Because the ABUS images can be visualized in transverse and coronal views, the proposed CNN provides an efficient way to extract multiview features from both views. The proposed CNN was trained and evaluated on 316 breast lesions (135 malignant and 181 benign). An observer performance test was conducted to compare five human reviewers' diagnostic performance before and after referring to the predicting outcomes of the proposed CNN. Our method achieved an area under the curve (AUC) value of 0.9468 with five-folder cross-validation, for which the sensitivity and specificity were 0.886 and 0.876, respectively. Compared with conventional machine learning-based feature extraction schemes, particularly principal component analysis (PCA) and histogram of oriented gradients (HOG), our method achieved a significant improvement in classification performance. The proposed CNN achieved a >10% increased AUC value compared with PCA and HOG. During the observer performance test, the diagnostic results of all human reviewers had increased AUC values and sensitivities after referring to the classification results of the proposed CNN, and four of the five human reviewers' AUCs were significantly improved. The proposed CNN employing a multiview strategy showed promise for the diagnosis of breast cancer, and could be used as a second reviewer for increasing diagnostic reliability., Competing Interests: Conflict of interest disclosure The authors declare that they have no conflicts of interest., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the predictive value of virtual monoenergetic images (VMIs) by assessing tumor conspicuity on dual-layer spectral detector CT (SDCT) and correlate tumor conspicuity on VMI with prognostic biomarkers in patients with breast cancer., Methods: Sixty-four patients underwent arterial phase and 90-s delayed phase dual-layer SDCT. A retrospective tumor conspicuity analysis of 14 benign tumors and 65 breast cancers was performed using conventional images (CIs) and VMI at 40 keV (VMI40) on arterial and delayed phase scans (CI ART , VMI40 ART , CI DE , VMI40 DE ). Mean Hounsfield units (HU) of tumors were measured on VMI40 ART and VMI40 DE . A receiver operating characteristic (ROC) curve analysis was performed to compare diagnostic accuracy between image sets. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 levels were evaluated using histopathology. Correlations between VMI analyses and histological characteristics of cancers were analyzed., Results: Cancers on VMI40 had a significantly higher conspicuity score and mean HU than benign tumors (p < 0.001). VMI40 DE showed the highest conspicuity for cancers (mean, 3.79) and the greatest area under the ROC curve (0.817; 95% confidence interval 0.745-0.889). VMI40 DE yielded significantly higher mean HU for cancers than VMI40 ART (p < 0.001). The conspicuity score and mean HU on VMI40 ART were significantly higher in cancers with ER negativity, PR negativity, and Ki67 positivity (p < 0.05)., Conclusions: VMI40 DE may be useful in the diagnosis of breast cancers due to higher tumor conspicuity and better enhancement than VMI40 ART . VMI40 ART may be beneficial for the prediction of poor breast cancer prognoses., Key Points: • VMI40 improved conspicuity of breast cancer than CI. • VMI40 DE yielded higher diagnostic performance of breast cancer than VMI40 ART . • VMI40 ART has an additional benefit in terms of prognosis prediction in patients with breast cancers.

Objective: Few studies have examined the effect of perceived social support (PSS) on chemotherapy-related symptoms (CRS). This study examined the effect of PSS on CRS in 184 patients with breast cancer., Methods: Participants were consecutively enrolled from a tertiary general hospital in Seoul, South Korea. CRS were assessed eight times, from before the first neoadjuvant chemotherapy to six months after the end of neoadjuvant chemotherapy, with the MD Anderson Symptom Inventory. PSS was evaluated once, before the first neoadjuvant chemotherapy session, using the Multidimensional Scale of Perceived Social Support (MSPSS). Two groups were formed based on MSPSS scores: the low PSS group (n = 62) and the moderate-to-high PSS group (n = 122). Linear mixed model analyses were used to compare the change in CRS severity between the two groups during chemotherapy., Results: Results indicated a significant group-by-time (low PSS or moderate-to-high PSS; 8 periods of chemotherapy) interaction for pain (p = .005), nausea (p = .033), insomnia (p < .001), distress (p = .003), dyspnea (p = .014), memory loss (p = .021), vomiting (p = .016), and numbness (p = .008) in which the moderate-to-high PSS group showed significantly lower levels of increase in those symptoms during chemotherapy. Moreover, the effect of PSS on CRS differed depending on the sources of PSS., Conclusion: Patients with moderate-to-high PSS experience less severe CRS compared with patients with low PSS during chemotherapy. The current findings indicate the potential benefits of providing social support in the management of CRS., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Although sentinel lymph node biopsy (SLNB) is the current standard for identifying lymph metastasis in breast cancer patients, there are complications of SLNB., Purpose: To evaluate preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) of invasive breast cancer for predicting sentinel lymph node metastasis., Study Type: Retrospective., Population: In all, 309 patients who underwent clinically node-negative invasive breast cancer surgery FIELD STRENGTH/SEQUENCE: 3.0T, DCE-MRI, DWI., Assessment: We collected clinicopathologic variables (age, histologic and nuclear grade, extensive intraductal carcinoma component, lymphovascular invasion, and immunohistochemical profiles) and preoperative MRI features (tumor size, background parenchymal enhancement, internal enhancement, adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, kinetic curve types, quantitative kinetic parameters, tumoral apparent diffusion coefficient [ADC], peritumoral maximal ADC, and peritumoral-tumoral ADC ratio)., Statistical Tests: Multivariate logistic regressions were performed to determine independent variables associated with SLN metastasis, and the area under the receiver operating characteristic curve (AUC) was analyzed for those variables., Results: 41 (13.3%) of the patients showed SLN metastasis. With MRI, tumor size (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.06-1.17), heterogeneous (OR, 5.33; 95% CI, 1.71-16.58), and rim (OR, 15.54; 95% CI, 2.12-113.72) enhancement and peritumoral-tumoral ADC ratio (OR, 72.79; 95% CI, 7.15-740.82) were independently associated with SLN metastasis. Clinicopathologic variables independently associated with SLN metastasis included age (OR, 0.96; 95% CI, 0.92-0.99) and CD31 (OR, 2.90; 95% CI, 1.04-8.92). The area under the curve (AUC) of MRI features (0.80; 95% CI, 0.73-0.87) was significantly higher than for clinicopathologic variables (0.68; 95% CI, 0.60-0.77; P = 0.048) and was barely below statistical significance for combined MRI features with clinicopathologic variables (0.84; 95% CI 0.78-0.90, P = 0.057)., Data Conclusion: Preoperative internal enhancement on DCE-MRI and peritumoral-tumoral ADC ratio on DWI might be useful for predicting SLN metastasis in patients with invasive breast cancer., Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:615-626., (© 2019 International Society for Magnetic Resonance in Medicine.)

Purpose: The aim of this study was to examine profiles of depressive symptoms and the association with anxiety and quality of life (QOL) in breast cancer survivors., Methods: A cross-sectional multicenter survey involving 5 hospitals in Korea was implemented between February 2015 and January 2017. A self-report survey included the Patient Health Questionnaire-9, Short Form 36, and State and Trait Anxiety Scale. Data from 347 patients were analyzed., Results: Latent profile analysis identified five profiles of depressive symptoms: (1) "no depression" (63.98%); (2) "mild depression with sleep problems" (16.43%); (3) "mild depression" (8.65%); (4) "moderate depression with anhedonia" (7.78%); and (5) "moderately severe depression" (3.17%). Results from Fisher's exact test and analysis of variance (ANOVA) to examine whether sociodemographic and clinical characteristics distinguish the classes indicated that marital status, income and education as well as C-reactive protein distinguished a few classes. Multivariate analysis of covariance and analysis of covariance results indicated that both types of anxiety as well as several dimensions of QOL differed between the identified classes., Conclusions: The current results suggest that although identified classes were characterized overall by severity of depression, a few classes also reflected pronounced individual symptom patterns, warranting tailored interventions for these symptom patterns, along with overall severity of depression.

Aquaporin-5 (AQP5) plays a role in breast cancer cell migration. This study aimed to identify AQP5-targeting miRNAs and examine their effects on breast cancer cell migration through exosome-mediated delivery. Bioinformatic analyses identified miR-1226-3p, miR-19a-3p, and miR-19b-3p as putative regulators of AQP5 mRNA. Immunoblotting revealed a decrease of AQP5 protein abundance when each of these miRNAs was transfected into human breast cancer MDA-MB-231 cells. Quantitative real-time PCR demonstrated the reduction of AQP5 mRNA expression by the transfection of miR-1226-3p and a luciferase reporter assay revealed the reduction of AQP5 translation after the transfection of miR-19b-3p in MDA-MB-231 cells. Consistently, the transfection of each miRNA impeded cell migration. Pathway enrichment analyses showed that these three miRNAs regulate target genes, which were predominantly enriched in the gap junction pathway. For the efficient delivery of AQP5-targeting miRNAs to breast cancer cells, exosomes expressing both miRNAs and a peptide targeting interleukin-4 receptor, which is highly expressed in breast cancer cells, were bioengineered and their inhibitory effects on AQP5 protein expression and cell migration were demonstrated in MDA-MB-231 cells. Taken together, AQP5-regulating miRNAs are identified, which could be exploited for the inhibition of breast cancer cell migration via the exosome-mediated delivery., (© 2020 Federation of American Societies for Experimental Biology.)

Purpose: To examine whether depression, anxiety disorder, and their co-occurrence would increase the risk of mortality in patients with breast cancer, and whether antidepressant treatment would reduce the same., Methods: Data were retrieved from the database of the Korean National Health Insurance Service. Of 145,251 patients diagnosed with breast cancer between 2007 and 2014, 20,870 patients diagnosed with depression or anxiety disorder one year before breast cancer diagnosis were excluded. Thus, data of 124,381 patients were included in this study., Results: Depression and anxiety disorder were associated with an increased risk of mortality [Hazard Ratio (HR) 1.26, 95% CI 1.18-1.36; HR 1.14, 95% CI 1.08-1.22, respectively] and their co-occurrence further increased the risk (HR = 1.38, 95% CI 1.24-1.54). Antidepressant treatment was related to a reduced risk of mortality. Compared to patients without any psychiatric comorbidity with no antidepressant treatment, the mortality risk increased in patients with either psychiatric comorbidity or both, but the risk seemed to attenuate with antidepressant treatments., Conclusion: The current findings suggest that psychiatric comorbidities are markers of increased mortality risk in patients with breast cancer, and antidepressant treatment may attenuate the risk. This underscores the need for screening and treating depression and anxiety disorders to improve survival in patients with breast cancer.

Objective: To develop a scoring system stratifying the malignancy risk of mammographic microcalcifications using the 5th edition of the Breast Imaging Reporting and Data System (BI-RADS)., Materials and Methods: One hundred ninety-four lesions with microcalcifications for which surgical excision was performed were independently reviewed by two radiologists according to the 5th edition of BI-RADS. Each category's positive predictive value (PPV) was calculated and a scoring system was developed using multivariate logistic regression. The scores for benign and malignant lesions or BI-RADS categories were compared using an independent t test or by ANOVA. The area under the receiver operating characteristic curve (AUROC) was assessed to determine the discriminatory ability of the scoring system. Our scoring system was validated using an external dataset., Results: After excision, 69 lesions were malignant (36%). The PPV of BI-RADS descriptors and categories for calcification showed significant differences. Using the developed scoring system, mean scores for benign and malignant lesions or BI-RADS categories were significantly different ( p < 0.001). The AUROC of our scoring system was 0.874 (95% confidence interval, 0.840-0.909) and the PPV of each BI-RADS category determined by the scoring system was as follows: category 3 (0%), 4A (6.8%), 4B (19.0%), 4C (68.2%), and 5 (100%). The validation set showed an AUROC of 0.905 and PPVs of 0%, 8.3%, 11.9%, 68.3%, and 94.7% for categories 3, 4A, 4B, 4C, and 5, respectively., Conclusion: A scoring system based on BI-RADS morphology and distribution descriptors could be used to stratify the malignancy risk of mammographic microcalcifications., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 The Korean Society of Radiology.)

Background: Breast cancer is the most common cancer among Asian women in the U.S. The first objective was to investigate predictors (including ethnicity) of never having a mammogram in middle-aged and older Chinese, Vietnamese, and Korean immigrant women (main effects). The second objective was to explore whether relationships between predictors and never having a mammogram varied across the three groups (moderation effects of ethnicity)., Methods: Merged (2005-2007-2009-2011) California Health Interview Survey data were utilized. Unweighted sample was 3,710 Asian women ages 40 years and older (Chinese = 1,389; Vietnamese = 1,094; Korean = 1,227). Replicate weighted total sample size was 1,710,233 (Chinese = 940,000; Vietnamese = 410,000; Korean = 360,000). Replicate-weighted multivariate logistic regression was applied. Interaction effects (moderator role of ethnicity) were also examined, using multivariate logistic regression, for the second objective., Results: For the first objective, odds of never having a mammogram were higher for women who were Korean (Ref = Vietnamese), unmarried, or a non-U.S. citizen. Odds were lower in women ages 50-59 or 60-69 (Ref = 70-85). Regarding the second objective, only for Chinese women, odds of never having a mammogram were lower as the number of physician visits got higher., Conclusion: Culturally-sensitive outreach and services should be developed to target higher-risk groups. Patient-centered healthcare strategies tailored for the three groups could be effective. For Chinese women, in particular, regular information sessions or education programs could be provided for enhancing their physician visits., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study was to determine whether disease recurrence and intrinsic characteristics of ductal carcinoma in situ (DCIS) are associated with the imaging method of detection in asymptomatic women. This multicenter, retrospective study included 844 women treated for asymptomatic DCIS who had pre-operative mammography and breast ultrasonography (US) studies available. Of the 844 women, 25 (3.0%) developed recurrences. Patients in the US group had significantly lower 5- and 10-y recurrence-free survival (RFS) rates compared with patients in the mammography group (p = 0.011). US-detected DCIS showed significantly lower 5-and 10-y RFS rates compared with mammography-detected DCIS in patients <50 y or with mammographically dense breasts (p = 0.002 and 0.002, respectively). US as the detection modality (hazard ratio [HR]: 4.451; 95% confidence interval [CI]: 1.530, 12.950; p = 0.006) and HER2 positivity (HR: 4.036; 95% CI: 1.438; 11.330; p = 0.008) were significantly associated with recurrence. We concluded that US as the detection modality and HER2 positivity were significantly associated with recurrence in patients treated for asymptomatic DCIS., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the interpretive performance and inter-observer agreement on digital mammographs among radiologists and to investigate whether radiologist characteristics affect performance and agreement., Materials and Methods: The test sets consisted of full-field digital mammograms and contained 12 cancer cases among 1000 total cases. Twelve radiologists independently interpreted all mammograms. Performance indicators included the recall rate, cancer detection rate (CDR), positive predictive value (PPV), sensitivity, specificity, false positive rate (FPR), and area under the receiver operating characteristic curve (AUC). Inter-radiologist agreement was measured. The reporting radiologist characteristics included number of years of experience interpreting mammography, fellowship training in breast imaging, and annual volume of mammography interpretation., Results: The mean and range of interpretive performance were as follows: recall rate, 7.5% (3.3-10.2%); CDR, 10.6 (8.0-12.0 per 1000 examinations); PPV, 15.9% (8.8-33.3%); sensitivity, 88.2% (66.7-100%); specificity, 93.5% (90.6-97.8%); FPR, 6.5% (2.2-9.4%); and AUC, 0.93 (0.82-0.99). Radiologists who annually interpreted more than 3000 screening mammograms tended to exhibit higher CDRs and sensitivities than those who interpreted fewer than 3000 mammograms ( p = 0.064). The inter-radiologist agreement showed a percent agreement of 77.2-88.8% and a kappa value of 0.27-0.34. Radiologist characteristics did not affect agreement., Conclusion: The interpretative performance of the radiologists fulfilled the mammography screening goal of the American College of Radiology, although there was inter-observer variability. Radiologists who interpreted more than 3000 screening mammograms annually tended to perform better than radiologists who did not., Competing Interests: The authors have no financial conflicts of interest., (Copyright © 2019 The Korean Society of Radiology.)

Rationale: Lymphangiomas develop in the head, neck, and axilla of patients <2 years old in more than 90% of cases. They are rarely reported in adults., Patient Concerns: Here, we report on a 37-year-old woman with a firm, hypoechoic 3.3 cm mass in the right upper, outer quadrant of the breast with discomfort, and swelling of the right axillary region., Diagnosis and Interventions: She underwent wide excision of the right breast and axillary lesion and the lesion pathologic finding is lymphangioma of the breast., Outcomes: She was in good condition with no signs of postoperative complications and no evidence of recurrence at 6 months postsurgery., Lessons: Despite the rarity of breast cystic lymphangioma, its evaluation should be considered for prompt diagnosis and definitive treatment to prevent recurrence and complications. Furthermore, this is the first case of concomitant lymphangioma of the breast parenchyma and axillary region.

Germline BRCA1 mutations predispose women to breast and ovarian cancer. BRCA1, a large protein with multiple functional domains, interacts with numerous proteins involved in many important biological processes and pathways. However, to date, the role of BRCA1 interactions at specific stages in the progression of mammary tumors, particularly in relation to cell cycle regulation, remains elusive. Here, we demonstrate that BRCA1 interacts with cyclin B1, a crucial cell cycle regulator, and that their interaction is modulated by DNA damage and cell cycle phase. In DNA-damaged mitotic cells, BRCA1 inhibits cytoplasmic transportation of cyclin B1, which prevents cyclin B1 degradation. Moreover, restoration of cyclin B1 in BRCA1-deficient cells reduced cell survival in association with induction of apoptosis. We further demonstrate that treatment of Brca1-mutant mammary tumors with vinblastine, which induces cyclin B1, significantly reduced tumor progression. In addition, a correlation analysis of vinblastine responses and gene expression profiles in tumors at baseline revealed 113 genes that were differentially expressed between tumors that did and did not respond to vinblastine treatment. Further analyses of protein-protein interaction networks revealed gene clusters related to vinblastine resistance, including nucleotide excision repair, epigenetic regulation, and the messenger RNA surveillance pathway. These findings enhance our understanding of how loss of BRCA1 disrupts mitosis regulation through dysregulation of cyclin B1 and provide evidence suggesting that targeting cyclin B1 may be useful in BRCA1-associated breast cancer therapy.

The pervasive role of microRNAs (miRNAs) in cancer pathobiology drives the introduction of new drug development approaches such as miRNA inhibition. In order to advance miRNA-therapeutics, meticulous screening strategies addressing specific tumor targets are needed. Small molecule inhibitors represent an attractive goal for these strategies. In this study, we devised a strategy to screen for small molecule inhibitors that specifically inhibit, directly or indirectly, miR-10b (SMIRs) which is overexpressed in metastatic tumors. We found that the multi-tyrosine kinase inhibitor linifanib could significantly inhibit miR-10b and reverse its oncogenic function in breast cancer and liver cancer both in vitro and in vivo. In addition, we showed that the efficacy of linifanib to inhibit tyrosine kinases was reduced by high miR-10b levels. When the level of miR-10b is high, it can "hijack" the linifanib and reduce its kinase inhibitory effects in cancer resulting in reduced anti-tumor efficacy. In conclusion, our study describes an effective strategy to screen for small molecule inhibitors of miRNAs. We further propose that miR-10b expression levels, due to the newly described "hijacking" effect, may be used as a biomarker to select patients for linifanib treatment.

Introduction: Annexin A3 (ANXA3) participates in various tumor-associated biological processes, including tumor initiation, progression, and metastasis. The present study was designed to investigate the expression and function of ANXA3 in breast cancer cells., Materials and Methods: Annexin A3 protein expression in breast cancer cell lines was evaluated using Western blot analysis. ANXA3 expression in MDA-MB 231 breast cancer cells was silenced by RNA interference, and the effects of RNA silencing on cell proliferation, colony forming ability, wound-healing, and invasiveness were evaluated. Levels of ANXA3 expression in 30 primary breast cancers were assayed using immunohistochemistry and correlated with patient survival., Results: Levels of ANXA3 expression were higher in the basal subtype of breast cancer cells, such as MDA-MB 231, HCC-70, and HCC-1954 cells, than in other subtypes. ANXA3 silencing inhibited the activities of MDA-MB 231 and HCC-1954 cells, including their proliferation, invasion across transwell membranes, and wound-healing and colony forming abilities. ANXA3 small interfering RNA (siRNA) also reduced the expression of cycle-dependent kinase protein and increased the expression of E2F1 and p27 proteins compared with control siRNA. Expression of ANXA3 was closely correlated with tumor size, with higher ANXA3 expression associated with reduced disease-free survival in breast cancer patients., Conclusion: These findings indicate that ANXA3 is associated with the natural progression of breast cancer and might be a potential prognostic marker of patient survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Fear of progression (FOP) is a prevalent concern among breast cancer patients that affect their adjustment to disease. This study examined whether self-efficacy moderates the effect of illness perception (IP) on FOP and whether the moderating effect of self-efficacy depends on the level of depressive symptoms., Methods: A cross-sectional survey including brief illness perception questionnaire (BIPQ), FOP short form, general self-efficacy scale, and the center for epidemiologic studies depression scale were administered to 245 patients with breast cancer in Korea., Results: Self-efficacy moderated the negative impact of the patients' perception of chronic timeline and a greater emotional impact of the illness on FOP. However, the moderating effect of self-efficacy of the BIPQ timeline and emotions on FOP depended on level of depressive symptoms., Conclusions: The findings underscore the importance of considering the IP as determinants of FOP, as well as of self-efficacy and depression as the moderating factors in the relationship between IP and FOP, suggesting the need to enhance self-efficacy and depressive symptoms in order to compensate the negative impact of IP on FOP in breast cancer patients., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objectives: To investigate the automated breast volume scanner (ABVS) in comparison with hand-held ultrasound (HHUS) according to the fifth edition of BI-RADS ultrasound., Material and Methods: A total of 831 lesions in 786 patients who underwent both HHUS and ABVS were included. Three radiologists independently evaluated the sonographic features of each lesion according to the fifth BI-RADS edition. The kappa coefficient (κ) was calculated for each BI-RADS descriptor and final assessment category. The accuracy of malignancy prediction and diagnostic performance of the BI-RADS descriptors were assessed using multivariate logistic regression and area under the receiver operator characteristic curve (AUC), respectively., Results: ABVS and HHUS showed moderate to good interobserver agreement (κ = 0.53-0.67 and 0.55-0.70, respectively) except in associated features (κ = 0.31 and 0.36, respectively) for BI-RADS lexicons. Irregular shape, a non-circumscribed margin, and posterior features (combined or shadowing) were independently associated with malignancy in both ABVS and HHUS. Calcification presence on ABVS (odds ratio [OR], 95% confidence interval [CI]: 2.09, 1.11-3.94) and non-parallel orientation on HHUS (OR, 95% CI: 2.04, 1.10-3.78) were independently associated with malignancy. There were no significant differences between ABVS and HHUS in sensitivity (84.2% vs. 84.2%), specificity (80.5% vs. 83.9%), or AUC (0.88 vs. 0.90)., Conclusions: According to the fifth BI-RADS edition, ABVS is not statistically significantly different from HHUS with regard to interobserver variability and diagnostic performance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Here the underlying role of CNOT2, a subunit of CCR4-NOT complex, was elucidated in cancer progression. CNOT2 was overexpressed in HIT-T15, ASPC-1, BXPC-3, PC-3, LNCaP, MCF-7 and MDA-MB-231 cell lines, which was confirmed by Tissue array in various human tumor tissues. Also, CNOT2 depletion suppressed proliferation and colony formation of MDA-MB-231 cells. Of note, microarray revealed decreased expression of CNOT2, VEGF-A, HIF2 alpha (<0.5 fold) and increased expression of UMOD1, LOC727847, MMP4, hCG and other genes (>2.0 fold) in CNOT2 depleted MDA-MB-231 cells compared to untreated control. Consistently, downregulation of VEGF, CNOT2 and HIF2 alpha was verified in CNOT2 depleted MDA-MB-231 cells by RT-qPCR. Additionally, CNOT2 depletion inhibited VEGF induced tube formation in HUVECs and reduced neovascularization in CAM assay. Furthermore, the growth of CNOT2 depleted MDA-MB-231 cells was significantly reduced in Balb/c nude mice along with decreased expression of VEGF and PCNA by immunohistochemistry compared to untreated control group. Overall, our findings provide evidences that CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells as a potent molecular target for breast cancer treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Trastuzumab has been widely used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer, however, it cannot easily cross the blood-brain barrier (BBB) and is known to increase the incidence of brain metastases. In contrast, lapatinib has a low molecular weight and can cross the BBB and it could be useful to treat brain metastases in patients with HER2-positive breast cancer.To explore the impact of lapatinib on radiation response, we conducted an in vitro experiment using SKBR3 and BT474 breast carcinoma cells exhibiting HER2/neu amplification. Lapatinib down-regulated phosphorylated (p)-HER2, p-epidermal growth factor receptor, p-AKT, and p-extracellular signal-regulated kinase. Pretreatment of lapatinib increased the radiosensitivity of SKBR3 (sensitizer enhancement ratio [SER]: 1.21 at a surviving fraction of 0.5) and BT474 (SER: 1.26 at a surviving fraction of 0.5) cells and hindered the repair of DNA damage, as suggested by the prolongation of radiation-induced γH2AX foci and the down-regulation of phosphorylated DNA-dependent protein kinase, catalytic subunit (p-DNAPKcs). Increases in radiation-induced apoptosis and senescence were suggested to be the major modes of cell death induced by the combination of lapatinib and radiation. Furthermore, lapatinib did not radiosensitize a HER2- negative breast cancer cell line or normal human astrocytes.These findings suggest that lapatinib can potentiate radiation-induced cell death in HER2-overexpressing breast cancer cells and may increase the efficacy of radiotherapy. A phase II clinical trial using lapatinib concurrently with whole-brain radiation therapy (WBRT) is currently being conducted.

Autophagy is a highly conserved mechanism that degrades long-lived proteins and dysfunctional organelles, and contributes to cell fate. In this study, autophagy attenuates Notch1 signaling by degrading the Notch1 intracellular domain (Notch1-IC). Nutrient-deprivation promotes Notch1-IC phosphorylation by MEKK1 and phosphorylated Notch1-IC is recognized by Fbw7 E3 ligase. The ubiquitination of Notch1-IC by Fbw7 is essential for the interaction between Notch1-IC and p62 and for the formation of aggregates. Inhibition of Notch1 signaling prevents the transformation of breast cancer cells, tumor progression, and metastasis. The expression of Notch1 and p62 is inversely correlated with Beclin1 expression in human breast cancer patients. These results show that autophagy inhibits Notch1 signaling by promoting Notch1-IC degradation and therefore plays a role in tumor suppression.

The aim of the study was to evaluate dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) features for the prediction of early and late recurrences in patients with breast cancer.Of 1030 breast cancer patients who underwent surgery at our hospital from January 2007 to July 2011, 83 recurrent breast cancer patients were enrolled in this study. We compared MRI features (background parenchymal enhancement [BPE], internal enhancement, adjacent vessel sign, whole-breast vascularity, initial enhancement pattern, kinetic curve types, and quantitative kinetic parameters) and clinico-pathologic variables (age, stage, histologic grade, nuclear grade, existence of lymphovascular invasion and extensive intraductal carcinoma component, and immunohistochemical profiles) between patients with early (≤2.5 years after surgery) and late recurrence (>2.5 years after surgery). Cox proportional hazard regression analysis was performed to evaluate independent risk factors for early and late recurrence.On breast MRI, prominent ipsilateral whole-breast vascularity was independently associated with early recurrence (hazard ratio [HR], 2.86; 95% confidence intervals [CI], 1.39-5.88) and moderate or marked BPE (HR, 2.08; 95% CI, 1.04-4.18) and rim enhancement (HR, 2.14; 95% CI, 1.00-4.59) were independently associated with late recurrence. Clinico-pathologic variables independently associated with early recurrence included negative estrogen receptor (HR, 0.53; 95% CI, 0.29-0.96), whereas T2 stage (HR, 2.08; 95% CI, 1.04-4.16) and nuclear grade III (HR, 2.54; 95% CI, 1.29-4.98) were associated with late recurrence.In DCE-MRI, prominent ipsilateral whole-breast vascularity, moderate or marked BPE, and rim enhancement could be useful for predicting recurrence timing in patients with breast cancer., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Background: Doctor-patient communication is a crucial aspect of patient care. This study explored the communication experience of patients in a cancer consultation over the course of the cancer continuum., Methods: In-depth interviews with seven breast cancer patients were carried out., Results: Themes related to communication experiences across the five phases of cancer consultation, from diagnosis to recurrence, were identified. The most salient issue is that patients also perceived cancer as 'a disease of the mind', which is not adequately cared for in consultation. This highlights the notion that cancer care providers should provide appropriate care for the psychological dimensions of the cancer experience with an empathic and sincere attitude during consultations. To this end, non-verbal aspects of communication that convey caring, support, and respect seem important. Furthermore, patients perceived that the consultation time was far shorter then they needed and reported that they felt pressured for time. Moreover, the stance taken by patients and the needs and preferences of patients varied across the phases of the cancer trajectory. As patients progressed through the phases of their treatment, they assumed more active roles in the course of their care and the need for more detailed information and questioning increased. Thus, ensuring that patients have opportunities to ask questions in the consultation is important., Conclusion: Current findings suggest that the efficacy of communication varies depending on which phase patients are in and that effective communication should be tailored to these evolving needs and preferences of breast cancer patients. Also, patients perceived that the consultation did not adequately address their need for information related to their care or their emotional issues associated with the cancer experience. It is therefore important to address their needs by paying particular attention to non-verbal aspects of communication that convey empathy and respect toward patients, as well as allowing patients to ask questions.

The receptor Notch1 plays an important role in malignant progression of many cancers, but its regulation is not fully understood. In this study, we report that the kinase HIPK2 is responsible for facilitating the Fbw7-dependent proteasomal degradation of Notch1 by phosphorylating its intracellular domain (Notch1-IC) within the Cdc4 phosphodegron motif. Notch1-IC expression was higher in cancer cells than normal cells. Under genotoxic stress, Notch1-IC was phosphorylated constitutively by HIPK2 and was maintained at a low level through proteasomal degradation. HIPK2 phosphorylated the residue T2512 in Notch1-IC. Somatic mutations near this residue rendered Notch1-IC resistant to degradation, as induced either by HIPK2 overexpression or adriamycin treatment. In revealing an important mechanism of Notch1 stability, the results of this study could offer a therapeutic strategy to block Notch1-dependent progression in many types of cancer. Cancer Res; 76(16); 4728-40. ©2016 AACR., (©2016 American Association for Cancer Research.)

Purpose/objectives: To investigate the relationships among life stress, family functioning, family coping, reliance on formal and informal resources, and decisional conflict in cancer survivors. 
., Design: Cross-sectional.
., Setting: Participants were recruited from the California Cancer Surveillance Program, hospital registries, and community agencies in southern California and Cleveland, Ohio. 
., Sample: 243 European American, African American, Chinese American, and Korean American cancer survivors diagnosed with breast, colorectal, or prostate cancer.
., Methods: The merged data from an ethnically diverse cohort of cancer survivors participating in the two survey studies were used. Standardized measures were used to identify family context variables and decisional conflict. 
., Main Research Variables: Life stress, family functioning, family coping, reliance on formal and informal resources, and decisional conflict.
., Findings: Structural equation modeling demonstrated that life stress was significantly associated with decisional conflict. Family functioning significantly mediated the impact of life stress on decisional conflict through family coping. Reliance on formal and informal resources moderated the relationships among the study variables. 
., Conclusions: The role of the family context, which includes family functioning and coping, on decisional conflict is important in the adjustment process to make high-quality decisions in cancer survivorship care. 
., Implications for Nursing: Findings present nursing practice and research implications that highlight the need for efforts to encourage and support family involvement in the decision-making process and to enhance cancer survivors' adjustment process.