Clinical Application of Multimodal Sentinel Lymph Node Mapping Method in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy: An Interim Analysis.

BACKGROUND: After neoadjuvant chemotherapy (NAC), the SLN identification rate is lower and has a higher false-negative rate than that at upfront surgery. This clinical trial aimed to confirm the effectiveness of sentinel lymph node (SLN) surgery by determining the lymph node identification rate using multimodal SLN marker methods in patients with advanced breast cancer undergoing NAC. PATIENTS AND METHODS: This clinical study is a prospective single-center randomized controlled trial involving patients with breast cancer receiving NAC. Patients are randomized (1:1:1) into arm A that involves the use of radioisotope (RI) plus indocyanine green fluorescence (ICG-F); arm B, RI plus vital dye; and, arm C, ICG-F plus vital dye. A total of 348 patients are needed. An interim analysis was performed on 50% of the patients enrolled. The primary outcome of this trial was the SLN identification rate. RESULTS: Among the 164 total patients (median age 51 years), T2 and N1 were the most common clinical stages. The identification rate of SLN was 95% in arm A, 92% in arm B, and 79% in arm C. To assess superior efficacy, the one-sided endpoint was set at α < 0.0056. Arms A and C showed a difference of 0.1597 in the detection rate (p = 0.0055). CONCLUSIONS: The use of ICG-F plus vital dye for SLNB was the least effective. The results show that the choice of tracer should be radioisotope in combination with one of the other tracers to have the highest SLN identification rate when SLNB cannot be implemented conventionally due to the circumstances of each institution.

Synthesis of Polyether, Poly(Ether Carbonate) and Poly(Ether Ester) Polyols Using Double Metal Cyanide Catalysts Bearing Organophosphorus Complexing Agents.

We developed a series of Zn(II)-Co(III) double metal cyanide (DMC) catalysts with exceptional activity for the ring-opening polymerization of various cyclic monomers by employing diverse organophosphorus compounds as complexing agents (CAs). The chemical structure and composition of DMC catalysts were investigated by commonly used analysis such as infrared and X-ray photoelectron spectroscopies, and elemental analysis combining with in situ NMR analysis to determine the complexation types of organophosphorus compounds the catalyst framework. The resulting catalysts exhibited very high turnover frequencies (up to 631.4 min-1) in the ring-opening polymerization (ROP) of propylene oxide and good efficiency for the ROP of ε-caprolactone. The resultant polyester polyols are suitable to use as an macroinitiator to produce well-defined poly(ester ether) triblock copolymers of 1800-6600 g mol-1 and dispersity of 1.16-1.37. Additionally, the DMC catalysts bearing organophosphorus compounds CAs exhibited remarkable selectivity for the copolymerization of PO with CO2, yielding poly(ether carbonate) polyols with carbonate contents up to 34.5%. This study contributes to the development of efficient DMC catalytic systems that enable the synthesis of high-quality polyols for various applications.

Clinical Features of Li-Fraumeni Syndrome in Korea.

PURPOSE: Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS. MATERIALS AND METHODS: Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected. RESULTS: Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively. CONCLUSION: This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

Breast density reduction as a predictor for prognosis in premenopausal women with estrogen receptor-positive breast cancer: an exploratory analysis of the updated ASTRRA study.

BACKGROUND: While the relationship between mammographic breast density reduction (MDR) and endocrine therapy efficacy has been reported in estrogen receptor (ER)-positive breast cancer, it is still unclear in premenopausal women, especially in the case of adding ovarian function suppression (OFS) to antihormone therapy. The authors investigated the impact of MDR on prognosis stratified by treatment based on the updated results of the ASTRRA trial. MATERIALS AND METHODS: The ASTRRA trial, a randomized phase III study, showed that adding OFS to tamoxifen (TAM) improved survival in premenopausal women with estrogen receptor-positive breast cancer after chemotherapy. The authors updated survival outcomes and assessed mammography before treatment and the annual follow-up mammography for up to 5 years after treatment initiation. Mammographic density (MD) was classified into four categories based on the Breast Imaging-Reporting and Data System. MDR-positivity was defined as a downgrade in MD grade on follow-up mammography up to 2 years after randomization, with pretreatment MD grade as a reference. RESULTS: The authors evaluated MDR in 944 of the 1282 patients from the trial, and 813 (86.2%) had grade III or IV MD. There was no difference in the MDR-positivity rate between the two treatment groups [TAM-only group (106/476 (22.3%)) vs. TAM+OFS group (89/468 (19.0%)); P =0.217). MDR-positivity was significantly associated with better disease-free survival (DFS) in the TAM+OFS group (estimated 8-year DFS: 93.1% in MDR-positive vs. 82.0% in MDR-negative patients; HR: 0.37; 95% CI: 0.16-0.85; P =0.019), but not in the TAM-only group ( Pinteraction =0.039). MDR-positive patients who received TAM+OFS had a favorable DFS compared to MDR-negative patients who received only TAM (HR: 0.30; 95% CI: 0.13-0.70; P =0.005). CONCLUSION: Although the proportion of MDR-positive patients was comparable between both treatment groups, MDR-positivity was independently associated with favorable outcomes only in the TAM+OFS group.

Ultraviolet-C light at 222 nm has a high disinfecting spectrum in environments contaminated by infectious pathogens, including SARS-CoV-2.

Ultraviolet light (UV) acts as a powerful disinfectant and can prevent contamination of personal hygiene from various contaminated environments. The 222-nm wavelength of UV-C has a highly effective sterilization activity and is safer than 275-nm UV-C. We investigated the irradiation efficacy of 222-nm UV-C against contaminating bacteria and viruses in liquid and fabric environments. We conducted colony-forming unit assays to determine the number of viable cells and a 50% tissue culture infectious dose assay to evaluate the virus titration. A minimum dose of 27 mJ/cm2 of 222-nm UV-C was required for >95% germicidal activity for gram-negative and -positive bacteria. A 25.1 mJ/cm2 dose could ensure >95% virucidal activity against low-pathogenic avian influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV-2). In addition, this energy dose of 222-nm UV-C effectively inactivated SARS-CoV-2 variants, Delta and Omicron. These results provide valuable information on the disinfection efficiency of 222-nm UV-C in bacterial and virus-contaminated environments and can also develop into a powerful tool for individual hygiene.

Health-related quality of life in long-term early-stage breast cancer survivors compared to general population in Korea.

PURPOSE: This study assessed health-related quality of life (HRQoL) of long-term breast cancer (BC) survivors diagnosed at early stages and compare with cancer-free, age-matched women. METHODS: The study population included BC survivors diagnosed with ductal carcinoma in situ (DCIS) or breast cancer stages I-II, who had undergone lumpectomy/mastectomy, with time since diagnosis ranging from 9 to 16 years. Survey was conducted at two tertiary hospitals in 2020. Data for cancer-free female controls was randomly drawn from a population-based survey and age-, education-matched with 1 case: 3 controls ratio. Self-reported HRQoL was assessed using EQ-5D with five dimentions. EQ-5D utility index score was calculated. Difference in EQ-5D score was evaluated using the Tobit regression model with adjustment for other covariates. RESULTS: Of 273 survivors. 88% and 12% underwent mastectomy and lumpectomy, respectively. The mean (standard deviation, SD) age at survey was 57.3 (8.5) years old. BC survivors reported significantly more problems performing daily activities (11% vs. 5%, p < 0.001), pain/discomfort (46% vs. 23%, p < 0.001), and anxious/depressed feelings (44% vs. 8%, p < 0.001) relative to the controls. Difference in EQ-5D score between BC survivors and the general population was higher in older age groups. The overall EQ-5D score of BC survivors was statistically lower than that of the control subjects (adjusted [Formula: see text]=0.117, p < 0.001). CONCLUSION: Long-term BC survivors who survived beyond ten years post-diagnosis experience more pain, anxiety, and distress, leading to an overall poorer HRQoL. IMPLICATIONS FOR CANCER SURVIVORS: This study suggest the importance of follow-up care, particularly focusing on pain, anxiety, and distress management to enhance the HRQoL of long-term BC survivors.

Characteristics of second primary breast cancer after ovarian cancer: a Korea central cancer registry retrospective study.

Background: Second primary cancer has become an important issue among cancer survivors. This study sought to determine the differences in clinicopathologic outcomes between second primary breast cancer (SPBC) after ovarian cancer and primary breast cancer (PBC) in the Republic of Korea. Methods and materials: We searched the Korea Central Cancer Registry and identified 251,244 breast cancer cases that were diagnosed between 1999 and 2017. The incident rate and standardized incidence ratio (SIR) were calculated. Demographic and clinical characteristics and overall survival (OS) rates were estimated according to age, histological type, and cancer stage. Results: Among the 228,329 patients included, 228,148 were patients with PBC, and 181 patients had SPBC diagnosed after ovarian cancer (OC). The mean ages at diagnosis were 56.09 ± 10.81 years for SPBC and 50.65 ± 11.40 years for PBC. Patients with SPBC were significantly less likely than patients with PBC to receive adjuvant radiotherapy (14.92% vs. 21.92%, p = 0.02) or adjuvant chemotherapy (44.75% vs. 55.69%, p < 0.01). Based on the age-standardized rate (ASR), the incidence of SPBC after OC was 293.58 per 100,000 ovarian cancer patients and the incidence of PBC was 39.13 per 100,000 women. The SIR for SPBC was 1.27 (1.09-1.46, 95% Confidence interval) in the patients overall. The 5-year OS rates were 72.88% and 89.37% for SPBC and PBC (p < 0.01). The OS rate in SPBC decreased significantly with advanced stage and older age. Conclusion: The incidence of breast cancer is about 1.27 times higher in ovarian cancer patients than in healthy people. The survival outcomes were worse for SPBC than for PBC and were related to older age and advanced stage. Active screening for breast cancer is necessary in ovarian cancer patients.

Questionnaire study of application about sentinel lymph node biopsy surgery in locally advanced breast cancer patients who received neoadjuvant chemotherapy.

Background: Nodal staging from sentinel lymph node (SLN) biopsy has become the standard procedure for early-stage breast cancer patients. SLN biopsy implementation after chemotherapy has previously been evaluated. This questionnaire study aimed to investigate the current trend of SLN biopsy after neoadjuvant chemotherapy (NAC) for locally advanced breast cancer. Methods and materials: We conducted a web-based survey among breast surgeons who are members of the Korean Breast Cancer Society. The survey comprised 14 questions about axillary surgery after NAC. Results: Of 135 respondents, 48.1% used a combined method of dye and radioactive isotope (RI). In the absence of SLN metastasis, 67.7% would perform only SLN biopsy, while 3% would perform ALN dissection. In case of SLN metastasis, the proportions of surgeons who would proceed with ALN dissection were 60.2% and 67.2% for less than two and more than three positive SLNs, respectively. Conclusion: The present study confirmed the increasing tendency to adopt SLN biopsy for axillary staging in patients who achieved complete response with initial nodal metastasis. It could be expected that the mapping methods for patients receiving NAC have become diverse, including RI, vital dye, and indocyanine green fluorescence. The implementation of SLN biopsy after NAC will grow in the coming years due to an increasing demand of minimally invasive surgery.

Clinicopathological Factors Associated with Oncotype DX Risk Group in Patients with ER+/HER2- Breast Cancer.

Oncotype DX (ODX), a 21-gene assay, predicts the recurrence risk in early breast cancer; however, it has high costs and long testing times. We aimed to identify clinicopathological factors that can predict the ODX risk group and serve as alternatives to the ODX test. This retrospective study included 547 estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and lymph node-negative breast cancer patients who underwent ODX testing. Based on the recurrence scores, three ODX risk categories (low: 0-15, intermediate: 16-25, and high: 26-100) were established in patients aged ≤50 years (n = 379), whereas two ODX risk categories (low: 0-25 and high: 26-100) were established in patients aged >50 years (n = 168). Factors selected for analysis included body mass index, menopausal status, type of surgery, and pathological and immunohistochemical features. The ODX risk groups showed significant association with histologic grade (p = 0.0002), progesterone receptor expression (p < 0.0001), Ki-67 (p < 0.0001), and p53 expression (p = 0.023) in patients aged ≤50 years. In patients aged >50 years, tumor size (p = 0.022), Ki-67 (p = 0.001), and p53 expression (p = 0.001) were significantly associated with the risk group. Certain clinicopathological factors can predict the ODX risk group and enable decision-making on adjuvant chemotherapy; these factors differ according to age.

Adding Ovarian Suppression to Tamoxifen for Premenopausal Women With Hormone Receptor-Positive Breast Cancer After Chemotherapy: An 8-Year Follow-Up of the ASTRRA Trial.

PURPOSE: To determine the updated long-term outcomes of the Addition of Ovarian Suppression to Tamoxifen in Young Women With Hormone-Sensitive Breast Cancer Who Remain Premenopausal or Regain Vaginal Bleeding After Chemotherapy (ASTRRA) trial. PATIENTS AND METHODS: This study is a post-trial follow-up of the ASTRRA trial, involving 1,483 premenopausal women younger than 45 years treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy for estrogen receptor-positive breast cancer. Patients were randomly assigned in a 1:1 ratio to complete 5 years of tamoxifen (TAM) alone (TAM-only) or 5 years of TAM with ovarian function suppression (OFS) for 2 years (TAM + OFS). The primary end point was disease-free survival (DFS), and the secondary end point was overall survival (OS). RESULTS: At 106.4 months of median follow-up, there was a continuous significant reduction in the DFS event rate in the TAM + OFS group. The 8-year DFS rate was 85.4% in the TAM + OFS group and 80.2% in the TAM-only group (hazard ratio [HR], 0.67; 95% CI, 0.51 to 0.87). There were no significant differences in OS between the two groups. The OS rate was 96.5% in the TAM + OFS group and 95.3% in the TAM-only group (HR, 0.78; 95% CI, 0.49 to 1.25). CONCLUSION: Adding OFS for 2 years to adjuvant TAM with a longer follow-up resulted in consistent DFS benefits, suggesting that adding OFS to TAM should be considered for patients who remain in a premenopausal state or resume ovarian function after chemotherapy.

Health-Seeking Behavior Returning to Normalcy Overcoming COVID-19 Threat in Breast Cancer.

PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has significantly impacted the diagnosis and treatment of breast cancer. Our study investigated the change in diagnosis and treatment of breast cancer with the progress of COVID-19 pandemic. MATERIALS AND METHODS: The study group comprised 6,514 recently diagnosed breast cancer patients between January 1, 2019, and February 28, 2021. The patients were divided into two groups: pre-COVID-19 period (3,182; January 2019 to December 2019) and COVID-19 pandemic period (3,332; January 2020 to February 2021). Clinicopathological information related to the first treatment after breast cancer diagnosis was retrospectively collected and analyzed in the two groups. RESULTS: Among the 6,514 breast cancer patients, 3,182 were in the pre-COVID-19 period and 3,332 were in the COVID-19 pandemic period. According to our evaluation, the least breast cancer diagnosis (21.8%) was seen in the first quarter of 2020. The diagnosis increased gradually except for the fourth quarter in 2020. While early-stage breast cancer was diagnosed 1,601 (48.1%) during the COVID-19 pandemic (p=0.001), the number of surgical treatments increased 4.6% (p < 0.001), and the treatment time was slightly shorter 2 days (p=0.001). The breast cancer subtype distribution was not statistically different between the pre-COVID-19 and COVID-19 period groups. CONCLUSION: In the early stages of the pandemic, the number of breast cancer cases temporarily decreased; however, they stabilized soon, and no significant differences could be identified in the diagnosis and treatment when compared to the period before the pandemic.

Progranulin and Breast Cancer Mortality: 13-Year Follow-Up of a Cohort Study.

Background: We have reported that serum progranulin (PGRN) levels are clinically significant in predicting recurrence in patients with HR-positive breast cancer. The aim of the present study was to examine whether PGRN levels might be associated with breast cancer mortality. Methods: This was a cohort study of 695 newly diagnosed breast cancer patients who underwent curative surgery between 2001 and 2004. The relationship between breast cancer mortality and pre-operative serum PGRN levels in these patients with a median follow-up of 12.7 years was evaluated until May 2020. Results: A total of 118 (17%) deaths were identified in the cohort. According to the HR status, (10, 15, and 20)-year overall survival (OS) rates were (91.4, 81.1, and 75.9) % for HR-positive patients, and (76.5, 74.2, and 69.8) % for HR-negative patients, respectively (p = 0.003). Higher levels of PGRN were significantly associated with poor OS in the HR-positive group (p for trend = 0.001). In particular, hazard ratios for PGRN quartiles suggested a dose-response relationship, with the highest quartile having the worst OS in the HR-positive group (highest vs lowest: 15-year OS, (68.3 vs 90.0) %; 20-year OS, (62.3 vs 84.8) %, even after adjusting for age, tumor stage, and metabolic confounders. Conclusion: Pre-operative serum PGRN levels had clinical significance for predicting cancer mortality in breast cancer patients independent of tumor stage and metabolic parameters, especially in HR-positive tumors.

Long-term trajectory of postoperative health-related quality of life in young breast cancer patients: a 15-year follow-up study.

PURPOSE: Breast cancer (BC) patients often experience various long-term sequelae due to aggressive treatment. We analyzed and illustrated long-term trajectory during different phases of treatment and survivorship. METHODS: Data were obtained from a cohort of 298 BC patients diagnosed between 2004 and 2006 and were followed up until 2020. We measured HRQoL using EORTC QLQ-C30, QLQ-BR23, and EuroQoL-5D questionnaires and conducted eight assessments right after initial diagnosis, during treatment, post-treatment, and during survivorship phases. Linear mixed model was used to assess changes in HRQoL. Overall HRQoL measured by EQ-5D index of long-term BC survivors were further compared with that of the age-matched general population. RESULTS: Of 298 participants, 246 women survived and 124 participated in the long-term follow-up survey (LTFU). Overall, HRQoL functions deteriorated during treatment but gradually improved between 1- and 3-year post-diagnosis and stabilized over LTFU measure. Significant recovery was observed in physical, role, emotional, social functions, and future perspectives (p < 0.05). Treatment-related acute symptoms were reported in the first year but diminished afterward, and treatment-related financial difficulties lessened. At LTFU, BC survivors reported a high level of insomnia, fatigue, and pain and appeared to have poorer overall HRQoL than the general population (mean difference, EQ-5D index: 0.073, p < 0.001). CONCLUSIONS: Through 15-year survivorship, BC survivors showed improvement in many aspects of HRQoL. However, some inferior aspects remain relevant for long-term survivors. Ongoing supportive programs concentrating on pain management, persistent cancer-related fatigue, and sleeping problems might aid enhance their HRQoL.

Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor-Positive and HER-2-Negative Breast Cancer with Neoadjuvant Chemotherapy.

PURPOSE: This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors. Materials and Methods: We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR. RESULTS: Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR-) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2-) subtype. The rate of pCR was 31.4% (196/624). AR- patients had a significantly higher rate of pCR than AR+ patients (AR- 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR- tumor showed higher pCR rate in HR+/HER2- subtype (AR- 28.6% vs. AR+ 7.3%, p=0.022). CONCLUSION: AR expression is predominant in the HR+/HER2- subtype. AR- is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2- subtype. When determining neoadjuvant chemotherapy for the HR+/HER2- subtype, AR expression can be considered as a pCR predictive marker.

Highly Active Heterogeneous Double Metal Cyanide Catalysts for Ring-Opening Polymerization of Cyclic Monomers.

A series of heterogeneous Zn-Co double metal cyanide (DMC) catalysts were investigated for ring-opening polymerization (ROP) of various cyclic monomers. Notably, inexpensive and commonly used organic solvents such as acetone, N,N-dimethylacetamide, N,N-dimethylformamide, dimethyl sulfoxide, nitromethane, and 1-methylpyrrolidin-2-one were very effective complexing agents for the preparation of DMC catalysts, showing high catalytic activity for the ROP of propylene oxide, ε-caprolactone, and δ-valerolactone. The chemical structures and compositions of the resultant catalysts were determined using various techniques such as FT-IR, X-ray photoelectron spectroscopy, powder X-ray diffraction, and elemental analysis. α,ω-Hydroxyl-functionalized polyether and polyester polyols with high yields and tunable molecular weights were synthesized in the presence of various initiators to control functionality. Kinetic studies of the ROP of δ-valerolactone were also performed to confirm the reaction mechanism.

Fear of Cancer Recurrence and Its Negative Impact on Health-Related Quality of Life in Long-term Breast Cancer Survivors.

PURPOSE: Fear of cancer recurrence (FCR) is a common psychological issue in breast cancer (BC) survivors during early survivorship but whether the same is true among long-term survivors has yet to be empirically evaluated. This study investigated FCR level, its associated factors, and impact on quality of life (QoL) in long-term BC survivors. MATERIALS AND METHODS: Participants included women diagnosed with BC between 2004 and 2010 at two tertiary hospitals. Survey was conducted in 2020. The study measured FCR with the Fear of Cancer Recurrence Inventory and other patient-reported outcomes, including depression and cancer-related QoL. Logistic regression was used to identify factors associated with FCR, and structural equation modeling was conducted to explore the impact of FCR on other outcomes. RESULTS: Of 333 participants, the mean age at diagnosis was 45.5, and 46% experienced FCR. Age at diagnosis ≤ 45 (adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.51 to 4.60), shorter time since diagnosis (aOR, 1.75, 95% CI, 1.08 to 2.89), and having a history of recurrence (aOR, 2.56; 95% CI, 1.16 to 5.65) was associated with more FCR. FCR was significantly associated with an increased risk of depression (ß=0.471, p < 0.001) and negatively impacted emotional functioning (ß=-0.531, p < 0.001). In addition, a higher FCR level may impair overall health-related QoL in long-term BC survivors (ß=-0.108, p=0.021). CONCLUSION: Ten years after diagnosis, long-term BC survivors still experienced a high level of FCR. Further, the negative impact of FCR on QoL and increased depression risk require an FCR screening and appropriate interventions to enhance long-term BC survivors' QoL.

Clinical Effectiveness of Hypofractionated Proton Beam Therapy for Liver Metastasis From Breast Cancer.

BACKGROUND: Few studies of proton beam therapy (PBT) for patients with liver metastasis from breast cancer (LMBC) are available to date. The aim of the present study was to evaluate the clinical effectiveness of PBT for patients with LMBC. MATERIAL AND METHODS: Seventeen patients with LMBC treated with PBT were included in this study. The median prescribed dose of PBT was 66 GyE (range, 60-80) in 10 fractions, 5 times a week. In patients with LMBC receiving PBT, freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were assessed. RESULTS: The median follow-up time was 34.2 months (range, 11.5-56.1). The median FFLP time was not yet reached, and the 3-year FFLP rates were 94.1% (95% confidence interval [CI], 82.9-105.3). The median times of PFS and OS were 7.9 months (95% CI, 5.3-10.5) and 39.3 months (95% CI, 33.2-51.9), respectively, and the 3-year PFS and OS rates were 19.6% (95% CI, -1.8-41.0) and 71.7% (95% CI, 46.8-96.6), respectively. Grade 3 or higher adverse events were not observed. CONCLUSION: PBT for patients with LMBC showed promising FFLP and OS with safe toxicity profiles. These findings suggest that PBT can be considered a local treatment option in patients with LMBC.

Surgical outcomes of localization using indocyanine green fluorescence in breast conserving surgery: a prospective study.

We investigated localization and safe resection margins for breast cancer patients undergoing breast conserving surgery (BCS) using ultrasound-guided indocyanine green fluorescence (ICG-F) marking. From April 2016 to March 2019, we prospectively enrolled 114 patients who underwent BCS using US-guided ICG-F marking and we compared these results with 300 patients who underwent BCS using US-guided skin marking from January 2012 to December 2016. Clinical features, identification rates, status of resection margins, and re-operation rates were analyzed. The ICG-F identification rate was 100% (114/114). The mean approach time for resection of the lesion ICG-F using group was about 13 min. The positive rate of frozen resection margins was 10.5% using ICG-F and 25.0% using sono-guided skin marking (p < 0.01). The rate of additional intraoperative resection was significantly lower in the ICG-F marking group compared to that in the sono-guided skin marking group (8.8% vs. 23.3%, p < 0.01). The rate of final positive resection margins was 3.5% in the ICG-F using group and 14.7% in the sono-guided skin marking group (p < 0.01). The rate of re-operation was 4.4% in the ICG-F using group and 4% in the sono-guided group (p = 0.79). At follow-up after the operation using ICG-F, no complications occurred. Using ICG-F during BCS could be a safe, sophisticated method for localization.

4-Phenylbutyric acid, a potent endoplasmic reticulum stress inhibitor, attenuates the severity of collagen-induced arthritis in mice via inhibition of proliferation and inflammatory responses of synovial fibroblasts.

4-Phenylbutyric acid (4-PBA) exerts potent pharmacological effects, including anti-inflammatory properties, via inhibition of endoplasmic reticulum (ER) stress. However, it is not known whether 4-PBA attenuates the severity of rheumatoid arthritis. The present study aimed to determine whether the inhibition of ER stress by 4-PBA ameliorated experimentally induced arthritis. The proliferation of synovial fibroblasts (SFs) and expression of matrix metalloproteinases (MMPs) were evaluated in the presence of interleukin (IL)-1ß with or without 4-PBA. The effect of 4-PBA on the phosphorylation of Mitogen-activated protein kinase (MAPK) and the activation of Nuclear factor-κB (NF-κB) in IL-1ß-stimulated SFs was assessed. In an in vivo study, the effects of 4-PBA were investigated using DBA/1 mice with collagen-induced arthritis (CIA). Clinical, histological, and serological assessments of CIA treated with 4-PBA were performed to determine the therapeutic effect of 4-PBA. In vitro, 4-PBA inhibited the proliferation and expression of IL-1ß-stimulated SFs and MMP-1 and MMP-3 through the suppression of both the phosphorylation of MAPKs and NF-κB in IL-1ß-stimulated SFs. The 4-PBA treatment markedly attenuated the severity of arthritis in CIA mice. The 4-PBA treatment ameliorated joint swelling and the degree of bone erosion and destruction and decreased the level of inflammatory cytokines and MMP-3 and Cox-2. Furthermore, remarkable improvements in histopathological findings occurred in 4-PBA-treated mice. These findings suggested that 4-PBA could attenuate the severity of arthritis in CIA mice by partially blocking the phosphorylation of MAPKs and the activation of NF-κB in SFs. Thus, through the inhibition of ER stress, 4-PBA may be a potent agent for the treatment of RA.

4-phenylbutyric acid mediates therapeutic effect in systemic lupus erythematosus: Observations in an experimental murine lupus model.

Impaired function of regulatory T cells (Tregs) contributes to the pathogenesis of systemic lupus erythematosus (SLE). Our previous study demonstrated aberrant responses of T lymphocytes to endoplasmic reticulum (ER) stress in patients with SLE. The present study investigated whether ER stress inhibition by 4-phenylbutyric acid (4-PBA) ameliorated lupus manifestations in an experimental lupus model and the effect of ER stress inhibition on the frequency and function of Tregs. A murine lupus model was induced through a 4-week treatment with Resiquimod, a toll-like receptor (TLR) 7 agonist. From the 8th week, the mice were treated with 4-PBA for 4 weeks. 4-PBA significantly decreased the levels of anti-dsDNA antibodies and serum TNF-α. A significant decrease in glomerulonephritis score was also observed in the 4-PBA-treated group. ER stress inhibition decreased the activated T and B lymphocytes population of splenocytes; however, the population of Tregs was not significantly different between the vehicle and 4-PBA group. However, a markedly enhanced suppressive capacity of Treg was detected in the 4-PBA-treated group. The present results suggest that ER stress inhibition attenuated disease activity in an experimental model by improving the suppressive capacity of Tregs. Therefore, reduction of ER stress could be used as a beneficial therapeutic strategy in SLE.