Psychological Impact of Type of Breast Cancer Surgery: A National Cohort Study.

BACKGROUND: The present study assessed the impact of different types of breast surgery on rates of psychological disorders in breast cancer patients. METHODS: This nationwide cohort study, based on Korean Health Insurance Review and Assessment Service claims data, included 26,259 breast patients who underwent surgery from June 1, 2017, to December 31, 2018. Associations between the incidence of psychological disorders and variables were evaluated by time dependent Cox regression analyses. RESULTS: Of the 26,259 patients, 9394 (35.8%) underwent total mastectomy (TM) and 16,865 (64.2%) underwent partial mastectomy (PM); of the former, 4056 (43.2%) underwent breast reconstruction surgery (RS). A total of 4685 patients (17.84%) were newly diagnosed with psychological disorders after surgery. Multivariable analysis showed that axillary lymph node dissection was significantly associated with increased rates of overall psychological disorders (p < 0.0001), depression (p = 0.0462), anxiety (p < 0.0001) and insomnia (p < 0.0001). The rates of overall psychological disorders (p = 0.0002) and insomnia (p = 0.01) were significantly lower in patients who underwent TM than PM. RS tended to associated with reduced rates of overall psychological disorders in patients who underwent TM. Subgroup analysis showed that, compared with PM, RS after TM significantly associated with a reduced incidence of overall psychological disorders and insomnia in younger patients (< 50 years) and those who underwent sentinel lymph node biopsy. CONCLUSION: In contrast to general belief, rates of overall psychological disorders and insomnia were lower in patients who underwent TM than PM. Moreover, RS after TM confers psychological benefit in younger patients with early stage breast cancer compared with PM.

Does the morphology of the umbilicus influence the incidence of surgical site infections in transumbilical single-incision laparoscopic appendectomy?

Background: Transumbilical laparoscopic appendectomy (TULA) may be a feasible alternative to conventional laparoscopic appendectomy. However, a transumbilical incision may increase incisional surgical site infections (SSIs) compared to conventional laparoscopic appendectomy. This study aimed to investigate the relationship between the morphology of the umbilicus and the incidence of SSIs in patients who underwent TULA. Patients and Methods: This retrospective study analysed the medical records of consecutive patients who underwent surgery for acute appendicitis at our institution from June 2016 to October 2020. The patients were assigned to the SSI group (those with an SSI) or the non-SSI group. The morphology of the umbilicus was calculated by measuring its width and depth on preoperative computed tomography images and was compared between the SSI and non-SSI groups. Results: The SSI group included 23 patients, while the non-SSI group included 252 patients. The width of the umbilicus was significantly shorter in the SSI group than in the non-SSI group (29 ± 10 mm vs. 34 ± 9 mm, P = 0.027). The umbilicus was slightly deeper in the SSI group than in the non-SSI group; however, the difference was not significant (16 mm vs. 15 mm, P = 0.384). Conclusions: This was the first study investigating the correlation between the morphology of the umbilicus and SSI development in TULA. SSIs tended to occur more commonly in a narrow and deep umbilicus. An extension of the umbilical incision may help prevent SSI in patients with this umbilical morphology.

Current Biomarkers for Precision Medicine in Breast Cancer.

Breast cancer has become the prototypical solid tumor where targets have been identified within the tumor allowing for personalized approach for systemic therapy. Biomarkers are beginning to play an important role in preparing the way for precision treatment. Mandatory biomarkers for every newly diagnosed case of breast cancer are estrogen receptors and progesterone receptors in selecting patients for endocrine treatment and HER2 for identifying patients likely to benefit from antiHER2 therapy. Although methodological problems exist in the determination of Ki67, because of its clearly established clinical value, wide availability, and low costs relative to the available multianalyte signatures, Ki67 may be used for determining prognosis, especially if values are low or high. Also, the androgen receptor (AR) pathway is emerging as a potential therapeutic target in breast cancer. AR-targeted treatments for breast cancer are in development and have shown promising preliminary results. While, most established biomarkers in breast cancer require tissue samples, serum tumor markers are easily accessible and require a less invasive procedure. Among them, tissue polypeptide-specific antigen (TPS), a specific epitope structure of a peptide in serum associated with human cytokeratin 18, is linked to the proliferative activity of tumors. TPS may be a valuable and independent prognostic biomarker for breast cancer.In order to accelerate progress towards precision treatment for women with breast cancer, we need additional predictive biomarker, especially for enhancing the positive predictive value for endocrine and antiHER2 therapies, as well as biomarkers for predicting response to specific forms of chemotherapy.

Transumbilical Single-Incision Laparoscopic-Assisted Appendectomy (TULAA) Is Useful in Adults and Young Adolescents: Comparison with Multi-Port Laparoscopic Appendectomy.

Background and objectives: Single-port laparoscopic appendectomy (SLA) in most previous studies has used intracorporeal excision of the appendix and needed a longer operative time than multi-port laparoscopic appendectomy (MLA), although SLA does have the potential benefit of an almost invisible scar within the umbilicus. Some studies have reported that extracorporeal transumbilical single-incision laparoscopic-assisted appendectomy (TULAA) in children took a considerably reduced operative time compared to MLA. We adopted TULAA in adults, adding routine dissection of the peritoneal attachment of the appendix. The aim was to compare the operative outcomes between TULAA and MLA. Materials and Methods: Between March 2013 and January 2016, 770 patients with acute uncomplicated and complicated appendicitis from 15 to 75 years of age were enrolled retrospectively. The operation was performed as early (EA) and interval appendectomy (IA). Results: Operative time was shorter in the TULAA group than in the MLA group, except for IA. No open conversion occurred in the TULAA group, except one case of ileocecal resection for IA. No intra-abdominal fluid collection was found in the TULAA group. Extended resection (especially partial cecectomy) was performed less frequently in the TULAA group than in the MLA group for IA. Mean postoperative hospital stay was shorter in the TULAA group for uncomplicated appendicitis. When the data of the EA group and the IA group were compared, operative time was significantly shorter in the IA group for both MLA and TULAA. The open conversion rate and the complication rate tended to be lower in the IA group. Confined to IA, the TULAA group tended to have shorter mean initial, postoperative, and total hospital stays. Conclusions: TULAA can be a useful surgical alternative to MLA in adults and young adolescents, because it lacks open conversion and provides both a shorter operative time and a shorter postoperative hospital stay. TULAA is feasible for IA in that it showed a lower rate of extended resection and complications.

Recurrent fusion transcripts detected by whole-transcriptome sequencing of 120 primary breast cancer samples.

Relatively few recurrent gene fusion events have been associated with breast cancer to date. In an effort to uncover novel fusion transcripts, we performed whole-transcriptome sequencing of 120 fresh-frozen primary breast cancer samples and five adjacent normal breast tissues using the Illumina HiSeq2000 platform. Three different fusion-detecting tools (deFuse, Chimerascan, and TopHatFusion) were used, and the results were compared. These tools detected 3,831, 6,630 and 516 fusion transcripts (FTs) overall. We primarily focused on the results obtained using the deFuse software. More FTs were identified from HER2 subtype breast cancer samples than from the luminal or triple-negative subtypes (P < 0.05). Seventy fusion candidates were selected for validation, and 32 (45.7%) were confirmed by RT-PCR and Sanger sequencing. Of the validated fusions, six were recurrent (found in 2 or more samples), three were in-frame (PRDX1-AKR1A1, TACSTD2-OMA1, and C2CD2-TFF1) and three were off-frame (CEACAM7-CEACAM6, CYP4X1-CYP4Z2P, and EEF1DP3-FRY). Notably, the novel read-through fusion, EEF1DP3-FRY, was identified and validated in 6.7% (8/120) of the breast cancer samples. This off-frame fusion results in early truncation of the FRY gene, which plays a key role in the structural integrity during mitosis. Three previously reported fusions, PPP1R1B-STARD3, MFGE8-HAPL, and ETV6-NTRK3, were detected in 8.3, 3.3, and 0.8% of the 120 samples, respectively, by both deFuse and Chimerascan. The recently reported MAGI3-AKT3 fusion was not detected in our analysis. Although future work will be needed to examine the biological significance of our new findings, we identified a number of novel fusions and confirmed some previously reported fusions.

Impact of Chemotherapy-Induced Ovarian Dysfunction on Response to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The association between chemotherapy-induced ovarian dysfunction (CIOD) and response to neoadjuvant chemotherapy (NAC) is not known. We therefore investigated the impact of CIOD on response to NAC in breast cancer patients according to estrogen receptor (ER) status. METHODS: In total, 343 premenopausal breast cancer patients treated with NAC between 2006 and 2010 were analyzed. Clinical responses were determined based on changes in tumor size measured using breast MRI. Patients with complete response or partial response were considered to have clinical response. RESULTS: After completion of NAC, 264 of 343 patients (76.9 %) developed CIOD. The clinical response rate was significantly higher in patients with CIOD than those without CIOD (65.2 vs. 51.9 %; p = 0.033). Additionally, the mean follicle-stimulating hormone (FSH) level after NAC was significantly higher in patients with clinical response (FSH 68.7 ± 34.5 vs. 59.8 ± 34.3 IU/L; p = 0.021). Multivariate analysis showed an independent association of CIOD to clinical response (OR 0.523, 95 % CI 0.297-0.918; p = 0.024). However, we observed no differences in the pathologic complete response (pCR) rate between patients with and without CIOD (8.7 vs. 6.3 %; p = 0.497). Subgroup analysis according to ER status showed that the association between CIOD and clinical response was significant in ER-positive but not ER-negative breast cancer (p = 0.025 and 0.818, respectively). CONCLUSIONS: CIOD during NAC is significantly associated with clinical response, but not pCR. Moreover, this association is only observed in ER-positive breast cancer, suggesting that the moderate difference in response to NAC is possibly a hormonal effect of chemotherapy-induced ovarian dysfunction.

The Value of Ki67 in Very Young Women with Hormone Receptor-Positive Breast Cancer: Retrospective Analysis of 9,321 Korean Women.

BACKGROUND: Young breast cancer patients have a poorer prognosis, especially when their tumors are hormone receptor positive. We analyzed the association between Ki67 and age and the impact of these factors on outcomes in hormone receptor-positive breast cancer. METHODS: The records of 9,321 hormone receptor-positive invasive breast cancer patients from three large centers were retrospectively reviewed. Each institution separately assayed Ki67 level immunohistochemically. Univariate and multivariate analysis for recurrence-free survival (RFS) was performed on 4,738 patients from a single center. RESULTS: Ki67 level was inversely proportional to age in all three data sets and was significantly higher for younger patients (p < 0.001, 0.03, and <0.001, respectively). This correlation was seen only in the human epidermal growth factor receptor 2 (HER2)-negative population. Survival analysis showed that both very young age (<35 years) and high Ki67 level (≥10 %) were independent prognostic factors. Although young age was a worse prognostic indicator regardless of HER2 status, Ki67 index was associated with worse prognosis only in HER2-negative patients. When patients were stratified into those with low and high Ki67, young age remained a significant factor for RFS, with hazard ratios in these two Ki67 groups of 2.15 and 2.57, respectively (p < 0.001). Also, the young age/low Ki67 group had significantly poorer RFS than the older age/high Ki67 group (p < 0.001). CONCLUSIONS: Ki67 level was higher in younger patients. However, very young patients had a poorer prognosis regardless of Ki67 level. Unknown biologic factors other than high cell proliferation might play a role in the aggressiveness of hormone receptor-positive breast cancer in very young patients.

Preoperative serum tissue polypeptide-specific antigen is a valuable prognostic marker in breast cancer.

Tissue polypeptide-specific antigen (TPS), a specific epitope structure of a peptide in serum associated with human cytokeratin 18, is linked to the proliferative activity of tumors. Here, we aimed to identify the association between the preoperative serum TPS level and outcome in breast cancer patients. We assayed preoperative serum TPS levels in 1,477 breast cancer patients treated between June 2000 and December 2006. The TPS level was measured with a one-step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cutoff value was 80 U/L. Among the 1,477 breast cancer patients examined, preoperative serum TPS level was elevated (>80 U/L) in 290 patients (19.6%). Age (>45 years), tumor size (>2 cm), nodal metastasis, negative progesterone receptor and human epidermal growth factor receptor 2 were associated with elevated TPS. Evidence of recurrence was observed in 229 patients (15.6%). Elevated TPS was associated with poor disease-free survival (p < 0.001) and overall survival (p < 0.001). In a multivariate analysis using the Cox proportional regression model, elevated TPS was an independent prognostic factor for disease-free survival (p = 0.001) and overall survival (p = 0.026). Furthermore, in subgroup analysis based on molecular subtype, the prognostic effect of preoperative TPS on survival (OS: HR 2.614, p = 0.003; DFS: HR 1.895, p = 0.001) was identified only in the luminal A subtype. Elevated preoperative serum TPS level is associated with poor breast cancer outcomes. Based on these findings, we conclude that preoperative TPS is a valuable biomarker for clinical use in predicting outcomes in breast cancer patients.

Breast cancer molecular phenotype and the use of HER2-targeted agents influence the accuracy of breast MRI after neoadjuvant chemotherapy.

OBJECTIVE: To investigate whether the accuracy of magnetic resonance imaging (MRI) after neoadjuvant systemic therapy (NST) is affected by molecular features of primary breast cancer and the use of human epidermal growth factor receptor 2 (HER2)-targeted agents. BACKGROUND: Improved understanding of factors affecting the accuracy of breast MRI after NST can lead to more tailored use of MRI in deciding surgical extent after NST. METHODS: We analyzed the imaging and clinicopathological data of 463 patients who underwent NST. We aimed to investigate whether the molecular subtypes, and the use of targeted therapies, were associated with changes in the accuracy of MRI predicting residual tumor extent. RESULTS: The accuracy of MRI predicting the residual tumor extent was most accurate in triple-negative breast cancer and was least accurate in Luminal A subtype (Pearson correlation coefficient of 0.754 and 0.531, respectively). Multivariate analysis suggested estrogen receptor (ER) status as an independent factor influencing the MRI accuracy. In HER2-amplified tumors, the use of HER2-targeted agents was associated with a less accurate MRI prediction. CONCLUSIONS: The accuracy of MRI in predicting residual tumor extent was lowest in ER-positive tumors treated with NST. In HER2-positive tumors, the use of HER2-targeted agents resulted in a less accurate MRI after NST. These factors should be considered for deciding the extent of breast conservation after neoadjuvant chemotherapy.

Prognostic effect of preoperative serum estradiol level in postmenopausal breast cancer.

BACKGROUND: The prognostic role of serum estrogen level in breast cancer patients is unclear. We investigated the prognostic importance of preoperative serum estradiol (E2) level in postmenopausal women according to their estrogen receptor (ER) status. METHODS: The medical records of 313 postmenopausal breast cancer patients who underwent surgery between 2006 and 2008 at a single institution were retrospectively evaluated. Patients who received neoadjuvant chemotherapy, synchronous bilateral breast cancer, or those with metastasis at diagnosis were excluded. Serum E2 and follicular stimulating hormone (FSH) levels were measured by radioimmunoassay and immunoradiometric assay, respectively, within 3 months prior to surgery. After a median follow-up of 52.0 months (11-77 months), 21 women were found to have metastatic disease. RESULTS: The overall, median E2 level was 13.0 pg/ml, and was slightly higher in ER-positive than ER-negative (p=0.69). The mean serum E2 level was significantly higher in patients with metastasis (17.41 ± 8.34 pg/ml) than in those without metastasis (13.54 ± 7.58 pg/ml) (p=0.02). Kaplan-Meier analysis using a cut-off of 13 pg/ml showed that, ER negative (p=0.02) but not ER positive (p>0.05) patients with higher E2 level showed significantly poorer metastasis-free survival. Multivariate analysis showed that, the high E2 level of ER negative tumors was an independent negative prognostic factor for metastasis- free survival (HR, 3.32; 95% CI, 1.05 to 10.51; p=0.04). CONCLUSIONS: Higher preoperative serum E2 level had a negative prognostic effect in postmenopausal women with breast cancer, especially in the ER-negative subgroup.

Prognostic influence of BCL2 expression in breast cancer.

Although BCL2 has occasionally been suggested as a candidate prognostic factor for breast cancer, it is still not accepted as a prognostic factor. We attempted to validate the role of BCL2 as a prognostic factor of breast cancer. Data on 7,230 primary breast cancer patients from the Seoul National University Hospital Breast Care Center were analyzed. Three current prognostic models, including the St. Gallen model, the Nottingham prognostic index (NPI) model and the TNM model, were used for analysis of the prognostic influence of BCL2. The positive BCL2 group showed more favorable features with regard to clinicopathologic parameters than the BCL2 negative group and a strong correlation was observed between BCL2 and the hormonal receptor. The positive BCL2 group showed better prognosis in overall survival and disease free survival (log-rank test, both p < 0.001), even in all subgroups, than the BCL2 negative group. BCL2 was a significant prognostic factor in both univariate (hazard ratio [HR], 0.361; 95% confidence interval (CI), 0.306-0.426; p < 0.001) and multivariate analyses (HR, 0.417; 95% CI, 0.417-0.705; p < 0.001). BCL2 had a strong influence on the established prognostic models, including the St. Gallen model, the NPI model and the TNM model. BCL2 was a powerful independent prognostic factor for breast cancer and had a strong influence on the current prognostic models. Favorable clinicopathologic features and a strong correlation with the hormonal receptor are suggested as the causes of superior survival in patients with BCL2 positive breast cancer.

Limited value and utility of breast MRI in patients undergoing breast-conserving cancer surgery.

BACKGROUND: Our aim was to compare the accuracy of magnetic resonance imaging (MRI) and ultrasonography (US) in measuring the size of invasive breast cancer (IBC) and carcinoma in situ (CIS). We also examined the utility of routinely performing MRI in addition to US before breast-conserving surgery (BCS). PATIENTS AND METHODS: Data from 1558 consecutive patients diagnosed with IBC and/or CIS between 2003 and 2005 were reviewed. For comparing the accuracy of US and MRI, paired t test was done comparing pathologic and imaging (US and MRI) tumor size in 821 patients who received both breast US and MRI. In instance of attempted BCS (n = 794), operative approach, resection margins, and clinical outcomes of non-MRI and MRI groups were compared. RESULTS: For CIS, IBC without CIS, and IBC with CIS, MRI was more accurate in estimating tumor size than US. When BCS was attempted (n = 794), the rate of tumor involvement in initial resection margins did not differ between non-MRI and MRI groups (23.0% and 23.4%, P = .926). Similarly, rates of re-excision (13.1% vs 17.5%, P = .130) and conversion to mastectomy (2.3% vs 2.1%, P = .893) were comparable, as were ipsilateral breast tumor recurrence, locoregional recurrence, and disease-free survival (log rank P = .284, .950, and .955, respectively). CONCLUSIONS: Breast MRI provided more accurate estimates of tumor size, correlating better with pathologic tumor size than US for both IBC and CIS. However, no clear benefit in terms of lower re-excision rate, higher breast conservation success, or reduced recurrence emerged for routine use of breast MRI before BCS.

The value of preoperative staging chest computed tomography to detect asymptomatic lung and liver metastasis in patients with primary breast carcinoma.

Little is known about the benefits of preoperative staging chest computed tomography (CT) in patients with asymptomatic breast cancer. We therefore investigated the clinical value of preoperative chest CT in detecting lung and liver metastases by retrospectively reviewing the records of 1,703 patients who underwent preoperative chest CT in a single institution between January 2006 and June 2009. Abnormal CT findings, including suspected metastases and indeterminate nodules in the lung or liver, were found in 266 patients (15.6%). Among these, 26 patients (1.5% of all patients and 9.8% of patients with abnormal CT findings) had true metastases, including 17 in the lungs, 3 in the liver, and 6 in both. True metastases were detected in 1 (0.2%), 0 (0%), and 24 (6.0%) patients with stage I, II, and III disease, respectively. The sensitivity, specificity, and positive predictive value of chest CT were 100, 89.1, and 11.3%, respectively, for lung metastasis and 100, 97.6, and 18.4%, respectively, for liver metastasis. All true metastatic lung lesions were all small-sized nodules, ranging from 0.2 to 1.5 cm in largest diameter, and could not be detected on chest X-rays. In conclusion, our results demonstrate the lack of usefulness of routine preoperative chest CT in detecting asymptomatic liver and lung metastasis in patients with early breast cancer. Chest CT, however, upstaged 6.0% of stage III patients to stage IV.

Young age is associated with ipsilateral breast tumor recurrence after breast conserving surgery and radiation therapy in patients with HER2-positive/ER-negative subtype.

Young breast cancer patients are more likely than old patients to experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS). However, the pathological processes underlying this relationship have not been elucidated. We investigated the effect of young age on IBTR in a Korean cohort of women with different molecular subtypes of breast cancer. We analyzed data of 2,102 consecutive breast cancer patients who underwent BCS and post-surgical radiation therapy (RT) at two Korean institutions between 2000 and 2005. Patients were classified as young (≤ 40 years; N = 513) or old (> 40 years; N = 1,589). Breast cancer subtype was determined by estrogen receptor (ER), progesterone receptor (PR), and HER2. Median follow-up duration was 61 months. The 5-year IBTR rate was 3.4% in young patients and 1.1% in old patients (P < 0.001). Univariate analysis indicated that IBTR rate in young patients with luminal A and HER2 subtypes was significantly greater than in old patients with these subtypes (P = 0.015 and P < 0.001, respectively). Multivariate analysis, which used luminal A subtype in old patients as reference, indicated that HER2 subtype in young patients was associated with increased risk of IBTR (hazard ratio, HR = 12.24; 95% CI: 2.54-57.96). Among old patients, HER2 subtype was not associated with increased IBTR. In conclusion, young women had a higher rate of IBTR after BCS and RT than old women. This difference is mainly among women with HER2 subtype. Aggressive local control and adjuvant therapy should be considered for young women with HER2 subtype breast cancer.

Clinicopathologic factors affecting discrepancies in HER2 overexpression between core needle biopsy and surgical biopsy in breast cancer patients according to neoadjuvant treatment or not.

Background: Accurate determination of human epidermal growth factor receptor 2 (HER2) status on breast core needle biopsy (CNB) tissue is important for determining neoadjuvant chemotherapies (NACs) for primary breast cancer. However, HER2 discrepancies occur before and after surgery, creating difficulties in the administration of appropriate NAC. This study aimed to identify the clinical factors affecting these discrepancies. Methods: This study was conducted on patients with primary breast cancer who underwent breast surgery from January 2012 to December 2018 at the Chung-Ang University Hospital. HER2 status was analyzed using immunohistochemistry. HER2 was graded as 0 to +3, and all 2+ cases were evaluated for gene amplification. The patients were divided into two groups based on whether or not they received chemotherapy. Patient and clinical characteristics between the two groups were compared using the χ2 test and a logistic regression model. Results: A total of 443 patients were evaluated; 384 patients (86.7%) did not receive NAC, and 59 patients (13.3%) received NAC. The HER2 discordance rate was 12.5% in the no NAC group and 23.7% in the NAC group. Most cases showed a change in HER2 status from negative in CNB to positive in surgical biopsy (SB). Clinicopathological factors affecting HER2 change in the no NAC group were larger tumor size and higher histologic grade. Meanwhile, poor response to prior chemotherapy affected HER2 change in NAC. Conclusion: The overall accuracy of CNB in determining HER2 status was lower in the NAC group than in the no NAC group. Some clinicopathological factors may affect HER2 changes in each group at different levels. Based on the HER2 status at the time of diagnosis, the choice of HER2-targeted therapy may vary, even if this is not true. Future research on the effects of changes in HER2 status between CNB and SB on prognosis is needed.

Soybeans ameliolate diabetic nephropathy in rats.

Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. Soybeans have been shown to reduce urinary albumin excretion and total cholesterol in non-diabetic patients with nephrotic syndrome. However, reports focusing specifically on diabetic nephropathy are scarce and the available results are inconsistent. It was reported that soybean consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas it was found to elicit an increase in urinary protein excretion when soybeans were consumed by type 2 diabetic patients. This study aims to investigate the effects of soybean in diabetic nephropathy, particularly the effects of consuming soybeans on the histopathology of diabetic nephropathy, using aquaporin (AQP) and osteopontin (OPN) expression as diagnostic markers. Male Sprague-Dawley rats were assigned to one of three groups: control, diabetic with red chow diet and diabetic with soybean diet. For histological examination, the expression of OPN and AQP, renal function and hemoglobin A1c were evaluated at the end of the study. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group given a soybean diet. OPN and AQP expression were suppressed in the kidney specimens of diabetic rats with the soybean diet. In conclusion, soybeans may prevent the weight loss and morphological disruption of the kidney associated with diabetes mellitus. Soybeans also may improve glycemic control. It seems likely that long-term control of blood glucose levels using a soybean diet could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented.

Global Trends in Immunotherapy Research on Breast Cancer over the Past 10 Years.

In recent years, many studies have focused on the host immune system and its relationship with tumor progression in a variety of solid tumors, including breast cancer. This study investigates recent trends of immunotherapy research in breast cancer and compares the contributions of research from different regions, institutions, and authors. A search of breast cancer and immunotherapy studies that were published between 2010 and 2019-with different keyword combinations-was performed in the Web of Science database. Bibliometric data were collected for analysis. VOSviewer software was used to generate a figure for the keyword's co-occurrence network, so as to implement network visualization analysis. A total of 1,041 publications were identified. The United States and China contributed to approximately 50% of the publications, 336 and 208, respectively. Both countries drove the increase in publications after 2015. A paper entitled "Pembrolizumab in patients with advanced triple-negative breast cancer: Phase IB KEYNOTE-012 Study" that was published in the Journal of Clinical Oncology by Nanda et al. was the most cited (715 citations). The keywords found in this research were grouped into four clusters: "mechanism," "vaccination," "PD-L1," and "chemotherapy." The terms "tumor-infiltrating lymphocytes" and "PD-1/PD-L1" are among the latest hotspots, which mostly appeared in 2017. Author keyword analysis revealed that recent trends in breast cancer immunotherapy focus on the triple-negative breast cancer subtype and PD-1/PD-L1 immune checkpoint pathway and inhibitors. This study analyzed global trends in immunotherapy research on breast cancer over the past 10 years and provided insight into the features and research hotspots of the articles in this issue.

Programmed cell death-ligand 1 expression in stromal immune cells is a marker of breast cancer outcome.

Purpose: The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in antitumor immune responses. However, there is considerable inconsistency regarding the prognostic value of PD-L1 expression status in breast cancer. We sought to evaluate the differential prognostic impacts of tumoral versus stromal immune cell PD-L1 expression in primary breast cancer. Materials & Methods: Both tumoral and stromal immune PD-L1 expression in formalin-fixed, paraffin-embedded tumor samples from 233 breast cancer patients without initial stage IV metastases were evaluated by immunohistochemistry using a mouse monoclonal anti-PDL1 antibody. Clinicopathological variables were also documented. A Cox regression model was used to assess the association of tumoral/stromal immune PD-L1 expression with clinical outcome using disease-free survival (DFS) as the primary end point. Results: Both tumoral and stromal immune PD-L1 expression were associated with aggressive tumor characteristics, including higher histologic grade, as well as negative estrogen receptor, negative progesterone receptor, and positive human epithelial growth factor receptor 2 (HER2) status Multivariate analyses further demonstrated that stromal immune cell, but not tumoral, PD-L1 expression was a favorable prognostic factor for survival. Conclusions: Despite its association with aggressive tumor features, PD-L1 expression on stromal immune cells emerged as a positive prognostic biomarker in breast cancer. This pro-survival effect might reflect the presence of a strong antitumor immune response that leads to PD-L1 expression.

Relationship between Mammographic Density and Age in the United Arab Emirates Population.

OBJECTIVE: Higher breast density is a strong, independent risk factor for breast cancer. Breast density varies by age, ethnicity, and geographic area although dense breast tissue has been associated with younger age and premenopausal status. The relationship between breast density and age in women in the United Arab Emirates (UAE) has not been determined. This study evaluated breast density in the UAE population and its relationship with age. METHODS: Women participating in the national cancer screening program from August 2015 to May 2018 who underwent screening mammography were included. Breast parenchymal density was classified according to the American College of Radiology (ACR) Breast Imaging-Reporting and Data System (BI-RADS) from category a (almost entirely fatty) through d (extremely dense). Subjects were divided into six age groups, and the association between age and breast density was evaluated. RESULTS: Of the 4911 women included, 1604 (32.7%), 2149 (43.8%), 1055 (21.5%), and 103 (2.1%) were classified as having categories a-d breast density, respectively. A significant negative correlation was observed between age and breast density category (p < 0.001). Women of mean age 44 ± 7 years had the highest breast density, whereas those of mean age 56 ± 14 years had the lowest breast density. Comparisons of Emirati women with Lebanese and Western women showed that breast density was lower in Emirati women than in the other populations. CONCLUSIONS: To our knowledge, this is the first study to evaluate the relationship between mammographic breast density and age in UAE women. As in other populations, age was inversely related to breast density, but the proportion of Emirati women with dense breasts was lower than in other populations. Because this study lacked demographic, clinical, and histopathological data, further evaluation is required.