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Retinal detachment and other vision-threatening disorders often necessitate vitreous body removal and tamponade injection for retina stabilization. Current clinical tamponades such as silicone oil and expansile gases have drawbacks, including patient discomfort and the need for secondary surgery. We introduce a transparent alginate-phenylboronic acid/polyvinyl alcohol composite hydrogel (TALPPH) as a novel vitreous substitute with tamponading capabilities. In vitro physicochemical, rheological, and optical characterization of in situ self-healable TALPPH was performed, and long-term biocompatibility was assessed in a rabbit model of vitrectomy retinal detachment. In vivo evaluations confirmed TALPPH's ability to inhibit retinal detachment recurrence and preserve rabbit vision without adverse effects. TALPPH's close resemblance to the natural vitreous body suggests potential as a vitreous tamponade substitute for future ophthalmological applications.
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Hidrogéis , Álcool de Polivinil , Descolamento Retiniano , Animais , Humanos , Coelhos , Hidrogéis/química , Descolamento Retiniano/complicações , Descolamento Retiniano/cirurgia , Alginatos/farmacologia , Corpo Vítreo , VitrectomiaRESUMO
PURPOSE: Pegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. MATERIALS AND METHODS: This was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. RESULTS: Pegfilgrastim administration reduced FN by 11.8-1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. CONCLUSION: The use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.
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Neoplasias da Mama , Neutropenia Febril , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Incidência , Estudos Prospectivos , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/epidemiologia , Neutropenia Febril/prevenção & controle , Dor , República da Coreia/epidemiologiaRESUMO
Background: In human epidermal growth factor receptor 2 (HER2)-positive early stage breast cancer, prediction of trastuzumab-related cardiac toxicity remains a challenge. The coronary calcium artery (CAC) reflects the total coronary plaque burden, which predicts the risk of atherosclerosis. We investigated the prediction of left ventricular ejection fraction (LVEF) decline in breast cancer according to CAC scores. Methods: A total of 347 patients were enrolled from Seoul St Mary's Hospital between January 2010 and December 2019. Chest computed tomography (CT) was performed at a single tertiary center. Patients who received trastuzumab for HER2-positive early breast cancer were included in this study. Results: Of the 347 patients, 312 and 35 had CAC scores of 0 and ≥1, respectively. The CAC ≥1 group was associated with older age, body mass index, and receipt of left breast irradiation. The CAC ≥1 group was significantly associated with LVEF decline (absolute value, ≤50%) (hazard ratio [HR] 12.038, 95% confidence interval [CI] 2.845-50.937, p = 0.001), LVEF decline (absolute value, ≤55%) (HR 4.439, 95% CI: 1.787-11.028, p = 0.001), and decline in LVEF of ≥10% points compared with baseline echography (HR 5.083, 95% CI: 1.658-15.582, p = 0.004). Even after adjusting for other clinical factors, CAC ≥1 remained a significant predictor of decreased LVEF. Conclusion: Our findings suggest that the CAC score is a significant predictor of cardiac toxicity following trastuzumab treatment in HER2-positive breast cancer. Therefore, CAC measurement could reduce cardiac toxicity by distinguishing patients at high risk for trastuzumab.
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PURPOSE: Although prospective randomized clinical trials have reported that the use of prophylactic tamoxifen in patients at a high risk of breast cancer is associated with an increased risk of cataracts development, such findings are inconsistent. This study aimed to clarify the relationship between adjuvant tamoxifen use and cataracts risk using a nationwide longitudinal population-based registry. METHODS: This retrospective cohort study was conducted using the Korean National Health Insurance claims database over a 15-year period (January 2007-December 2021). Data from all female patients diagnosed with ductal carcinoma in situ (DCIS) between 2009 and 2015 were extracted. We evaluated the incidence of cataracts diagnosis and surgery after adjuvant tamoxifen administration in patients with DCIS. RESULTS: A total of 43,434 patients who met the inclusion criteria were diagnosed with DCIS between 2009 and 2015. Data from 2849 patients receiving tamoxifen and 1615 patients not receiving tamoxifen were analyzed before matching. After matching for comorbidities, type of breast surgery, and age, both groups consisted of 1597 patients. Both before and after matching, adjuvant tamoxifen was not a significant factor for an increased risk of cataracts diagnosis alone or with surgery. CONCLUSION: Our study showed that adjuvant tamoxifen was not a risk factor for increased cataracts diagnosis and surgery in patients with DCIS. This finding provides a basis for physicians to reduce their ocular toxicity concerns regarding the risk of patients developing cataracts by tamoxifen treatment.
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Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Catarata , Feminino , Humanos , Tamoxifeno/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Estudos de Coortes , Estudos Retrospectivos , Estudos Prospectivos , Catarata/induzido quimicamente , Catarata/epidemiologia , Catarata/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Mastectomia SegmentarRESUMO
PURPOSE: An inverse relationship between cancer and neurodegenerative disease, which presents the possibility of a reduced risk of dementia in cancer patients, has been suggested previously. However, a nationwide longitudinal population-based study of specific types of cancer with due consideration of treatment effects has not been conducted. Materials and Methods: This nationwide population-based cohort study used data obtained in a 12-year period (January 2007- December 2018) in the Korean National Health Insurance claims database. All female breast cancer patients (age ≥ 50 years) diagnosed between 2009 and 2010 were included after excluding those with physician visits for any cancer during a 2-year period (2007-2008). Patients with senile cataract constituted the control group. The main study outcome was the risk of developing dementia. RESULTS: From a total of 90,396 and 85,906 patients with breast cancer and cataract, respectively, patients without behavior codes were excluded. Data for 15,407 breast cancer patients and 7,020 controls were analyzed before matching. After matching for comorbidities and age, either group comprised 2,252 patients. The median follow-up time was 104.1±24.0 months after matching. After matching, breast cancer was a predictor of a lower risk of for dementia (hazard ratio, 0.091; 95% confidence interval, 0.075 to 0.111; p < 0.001). In breast cancer patients, receiving chemotherapy and endocrine therapy did not significantly affect the incidence of dementia. CONCLUSION: Breast cancer was associated with a remarkably decreased risk of dementia. The findings strongly suggest an inverse relationship between cancer and neurodegeneration, regardless of the adverse effects of cancer treatment on cognitive function.
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Neoplasias da Mama , Catarata , Demência , Doenças Neurodegenerativas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/tratamento farmacológico , Estudos de Coortes , Incidência , Catarata/epidemiologia , Demência/epidemiologia , Demência/etiologia , Demência/diagnóstico , Fatores de Risco , Estudos RetrospectivosRESUMO
Introduction: The partial estrogen-agonist action of tamoxifen on bone receptors has beneficial effects on bone mineral density. However, in premenopausal women, the use of tamoxifen causes systemic estrogen depletion, which has detrimental effects on bone health. We aim to investigate the association between tamoxifen and osteoporosis in the real world using data from a longitudinal nationwide cohort of Korean patients. Methods: Data were collected from the National Health Insurance claims database in South Korea. Osteoporosis was defined by diagnostic codes accompanying prescription data for osteoporosis. The cumulative incidence was analyzed by Kaplan-Meier survival curves and the risk factors were analyzed using a multivariable Cox proportional hazard regression model. Results: Between 2009 and 2015, of the 4,654 women with ductal carcinoma in situ (DCIS) without prior osteoporosis, 2,970 were prescribed tamoxifen and 1,684 were not. A total of 356 DCIS survivors were later diagnosed with osteoporosis during a median follow-up period of 84 months. In the overall population, tamoxifen was associated with a low risk of osteoporosis, before and after propensity matching adjusted for age, operation type, and comorbidities (before matching, hazard ratio [HR]=0.69, 95% confidence interval [CI]=0.559-0.851, p<0.001; after matching, HR=0.664, 95% CI=0.513-0.858, p=0.002). In the subgroup analysis, findings were consistent in postmenopausal women but were not evident in the younger age group. Conclusion: In a nationwide cohort study, a low risk of osteoporosis was associated with the use of tamoxifen. The protective effect of tamoxifen was more profound in older women and was not related to the incidence of osteoporosis in younger women.
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Glucose utilization by visceral adipose tissue (VAT) reflects inflammatory activity, which also promotes tumor growth and carcinogenesis. The effect of metabolically active VAT on survival outcomes in breast cancer is unknown. We investigated survival outcomes in patients with breast cancer based on the standardized uptake value (SUV) of VAT (SUVmean-VAT) using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). A total of 148 patients with breast cancer were divided into high- and low groups according to their SUVmean-VAT and SUVmax-tumor. Clinical characteristics and survival outcomes were compared between the groups. High SUVmean-VAT was associated with poor recurrence-free survival (RFS; hazard ratio [HR], 2.754; 95% confidence interval [CI], 1.090-6.958, p = 0.032) and distant metastasis-free survival (DMFS; HR, 3.500; 95% CI, 1.224-10.01, p = 0.019). Multivariate analysis showed that high SUVmean-VAT was a significant factor for poor RFS and poor DMFS (p = 0.023 and 0.039, respectively). High SUVmax-tumor was significantly associated with short RFS (p = 0.0388). Tumors with a high SUV tended to have a short DMFS, although the difference was not significant (p = 0.0718). Our findings showed that upregulated glucose metabolism in the VAT measured using 18F-FDG PET/CT may be a prognostic biomarker for adverse outcomes in breast cancer.
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Neoplasias da Mama , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Gordura Intra-Abdominal/diagnóstico por imagemRESUMO
(1) Background: Residual breast cancer after neoadjuvant chemotherapy (NAC) could have a variable image pattern on a follow-up breast magnetic resonance image (MRI). In this study, we compared the clinical outcome of breast cancer patients with different residual tumor patterns (RTP) on a breast MRI after NAC. (2) Methods: A total of 91 patients with breast cancer who received NAC and subsequent curative surgery were selected. All included patient had residual breast cancer after NAC and showed a partial response on a breast MRI. Pre- and post-treatment were reviewed by an experienced radiologist to evaluate different RTP, and classified into two groups: concentric and scattered patterns. The clinicopathologic parameters and survival outcomes [recurrence-free survival (RFS) and distant metastasis-free survival (DMFS)] were analyzed according to different RTP. (3) Results: Patients with a scattered pattern had a larger extent of pre-treated non-mass enhancement and more frequently received total mastectomy. With a median follow-up period of 37 months, RTP were not significantly associated with RFS or DMFS. (4) Conclusions: In the patients with residual breast cancer after NAC, RTP on an MRI had no effect on the patients' clinical outcome. The curative resection of the tumor bed and securing the negative resection margins appear to be important in the treatment of patients with residual breast cancer after NAC.
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Background: Although previous studies demonstrated no association between depression and tamoxifen in patients with breast cancer, there is still a limited amount of long-term follow-up data. This study aimed to evaluate the relationship between endocrine treatment and the risk of depression. Methods: This nationwide population-based cohort study used data obtained over a 14-year period (January 2007 to December 2021) from the Korean National Health Insurance claims database. All female patients with breast cancer were included. We examined the incidence of depression in patients who underwent endocrine treatment, and those who did not undergo endocrine treatment constituted the control group. Results: The data from 11,109 patients who underwent endocrine treatment and 6,615 control patients between 2009 and 2010 were analyzed. After performing matching for comorbidities and age, both groups comprised 6,532 patients. The median follow-up were 119.71 months. Before and after matching was performed, the endocrine treatment was not a significant risk factor for developing depression (p=0.7295 and p=0.2668, respectively), nor was it a significant factor for an increased risk for suicide attempt (p=0.6381 and p=0.8366, respectively). Conclusions: Using a real-world population-based cohort, this study demonstrated that there is no evidence that the endocrine treatment increases the risk of depression.
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BACKGROUND: Older patients with breast cancer have good prognosis and most die from diseases other than breast cancer. Previous studies suggested that the surgical extent in older patients could be reduced. We aimed to compare survival outcomes in patients aged ≥70 years with clinically node-negative breast cancer, based on whether axillary surgery was performed. METHODS: A total of 2,995 patients with breast cancer aged ≥70 years who underwent breast surgery were included in the Korean Breast Cancer Registry. Patients were classified into two groups according to the performance of axillary surgery. We used propensity score matching for demographic and treatment factors to minimize selection bias. We compared the 5-year overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: Among 708 patients after 3:1 propensity score matching, 531 underwent breast surgery with axillary surgery and 177 underwent breast surgery alone. Of all patients, 51.7% had T1 stage, and 73.2% underwent mastectomy. Approximately 31.2% of patients received chemotherapy. Among patients who did not undergo axillary surgery, the 5-year OS and BCSS rates were 85.2% and 96.7%, respectively. The hazard ratio of axillary surgery for OS was 0.943 (95% confidence interval 0.652-1.365, p = 0.757), indicating no significant difference between two groups. CONCLUSIONS: Our study demonstrates that axillary surgery in a matched cohort of older patients with breast cancer and clinically negative nodes does not provide a survival benefit compared to patients undergoing breast surgery alone. These findings suggest that axillary surgery may be safely omitted in a select group of patients aged ≥70 years with clinically node-negative cancer. Further studies are needed to identify potential candidates for omitting axillary surgery.
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Neoplasias da Mama , Humanos , Idoso , Feminino , Neoplasias da Mama/cirurgia , Mastectomia , Excisão de Linfonodo , Axila , Modelos de Riscos ProporcionaisRESUMO
Despite being a standard treatment option in breast cancer, immune checkpoint inhibitors (ICIs) are only efficacious for a subset of patients. To gain a better understanding of the antitumor immune response in breast cancer, we examined the heterogeneity of CD8+ T cells in tumors, metastatic lymph nodes (mLNs), and peripheral blood from patients with early breast cancer (n = 131). Among tissue-resident memory CD8+ T (TRM) cells, including virus- and tumor-specific CD8+ T cells, CD39 expression was observed in a tumor-specific and exhausted subpopulation in both tumors and mLNs. CD39+ TRM cells from tumors and mLNs exhibited a phenotypic similarity and clonally overlapped with each other. Moreover, tumor or mLN CD39+ TRM cells clonally overlapped with CD39- TRM and non-TRM cells in the same compartment, implying a tissue-specific differentiation process. These inter-subpopulationally overlapping CD39+ TRM clonotypes were frequently detected among effector memory CD8+ T cells in peripheral blood, suggesting a systemic clonal overlap. CD39+ TRM cell enrichment was heterogeneous among molecular subtypes of breast cancer, which is associated with the different role of antitumor immune responses in each subtype. In vitro blockade of PD-1 and/or CTLA-4 effectively restored proliferation of CD39+ TRM cells and enhanced cytokine production by CD8+ T cells from tumors or mLNs, particularly in the presence of CD39+ TRM enrichment. This suggests that CD39+ TRM cells have a capacity for functional restoration upon ICI treatment. Thus, our study indicates that CD39+ TRM cells with a clonal overlap across compartments are key players in antitumor immunity in breast cancer.
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Neoplasias da Mama , Linfócitos T CD8-Positivos , Feminino , Humanos , Imunoterapia , LinfonodosRESUMO
PURPOSE: The aim of this study was to evaluate the radiological response rate patterns during neoadjuvant chemotherapy (NAC) in patients with breast cancer. METHODS: Patients who underwent NAC with two specific chemotherapy regimens (doxorubicin with cyclophosphamide or doxorubicin with docetaxel) and who underwent a response evaluation every two cycles were included in the study. The initial response ratio was defined as the ratio of the largest tumor diameter at diagnosis to that after two cycles of NAC. The latter response ratio was defined as the ratio between the tumor size after two cycles and that after four cycles of NAC. The radiological response rate pattern was divided into three groups: the fast-to-slow response group (F-S group, initial response ratio > latter response ratio + 20%), slow-to-fast response group (S-F group, latter response ratio > initial response ratio + 20%), and constant response group (less than 20% difference between the initial and latter response ratios). RESULTS: In total, 177 patients were included in the analysis. Forty-two (23.9%) patients were categorized into the F-S group, 26 (14.8%) into the S-F group, and 108 (61.2%) into the constant group. Clinicopathologic factors did not differ according to radiologic response rate patterns. The median follow-up period was 50 months (range, 3-112) months. In the univariate analysis, the F-S group had a significantly worse recurrence-free survival than the S-F and constant groups (hazard ratio [HR], 3.63; 95% confidence interval [CI], 1.05-12.46; p = 0.041). The F-S group also presented with significantly worse survival than the S-F group in the multivariate analysis (HR, 3.45; 95% CI, 1.00-11.89; p = 0.049). CONCLUSION: The F-S group had a poorer survival rate than the S-F group. Radiological response rate patterns may be useful for accurate prognostic assessments, especially when considering post-neoadjuvant therapy.
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Purpose: After the publication of the ACOSOG (American College of Surgeons Oncology Group) Z0011 trial, the rate of axillary lymph node dissection has reduced. Thus, the need for intraoperative frozen section biopsy of sentinel lymph nodes (SLNs) has become controversial. We identified patients for whom intraoperative SLN frozen section biopsy could be omitted and found that frozen section biopsy rate can be reduced. Methods: We reviewed the records of patients with tumors ≤5 cm in diameter who underwent breast-conserving surgery between January 2013 and December 2019 at Seoul St. Mary's Hospital. Clinicopathological and imaging characteristics were compared according to number of positive SLNs (0-2 SLNs positive vs. ≥3 SLNs positive). Results: A total of 1,983 patients were included in this study. Thirty-two patients (1.6%) had at least 3 positive SLNs. Patients with ≥3 positive SLNs had significantly larger tumors and were more frequently high-grade tumors (P < 0.001 and P = 0.002, respectively). Identification of suspicious lymph nodes on imaging studies was also associated with the presence of ≥3 positive SLNs (hazard ratio, 11.54; 95% confidence interval, 4.42-30.10). All patients with none or only 1 suspicious lymph node on any imaging modality (n = 647, 32.6%) had 0-2 positive SLNs. Also, among patients with clinical T1-stage tumors and at least 2 suspicious lymph nodes on only 1 imaging modality (n = 514, 25.9%), only 2 cases had ≥3 positive SLNs. Conclusion: We found that intraoperative SLN frozen biopsy could be omitted in patients using tumor size and axillary lymph node status on imaging modality.
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PURPOSE: Radiation-induced anti-tumor responses occur in the immune system, particularly in peripheral blood mononuclear cells (PBMCs), which are overly sensitive to ionizing radiation. Irradiation of PBMCs is associated with inflammation. We assessed the association between radiotherapy (RT)-induced changes in peripheral blood cells, utilizing the lymphocyte-to-monocyte ratio (LMR), and survival outcome in breast cancer patients who underwent breast-conserving surgery followed by adjuvant RT. METHODS: LMR values were obtained from retrospective data, and serial sampling of blood before the first and last RT sessions was performed. The cut-off point was analyzed using the Youden index and receiver operating characteristic curve. Recurrence-free survival (RFS) and overall survival (OS) were the main outcomes. RESULTS: Patients with RT-induced low LMR had significantly shorter RFS (hazard ratio [HR] 2.730; 95% confidence interval [CI], 1.607-4.636, P = 0.0002) and OS (HR 2.890; 95% CI 1.410-5.924, P = 0.0038). The results were more robust in the subgroup of patients who received chemotherapy. Multivariate analysis showed that lymph node metastasis and RT-induced low LMR were associated with poor RFS (HR 1.763; 95% CI, 1.017-3.059, P = 0.044) and OS (HR 2.254; 95% CI, 1.060-4.796, P = 0.035). CONCLUSION: This study demonstrates that RT-induced low LMR is a valid prognostic marker for recurrence and survival in breast cancer patients undergoing RT.
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Neoplasias da Mama , Monócitos , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Humanos , Leucócitos Mononucleares , Linfócitos/patologia , Prognóstico , Estudos RetrospectivosRESUMO
Purpose: Although adjuvant chemotherapy (CTx) is still recommended for high-risk patients with hormone receptor-positive and human epidermal receptor (HER)-2-negative breast cancer, recent studies found that selected patients with low disease burden may be spared from CTx and receive hormonal treatment (HT) alone. This study aims to evaluate the trends of treatment (CTx + HT vs. HT alone) in Korea and to assess the impact on overall survival (OS) according to treatment pattern. Methods: The Korean Breast Cancer Society Registry was queried (2000 to 2018) for women with pT1-2N0-1 hormone receptor-positive and HER2-negative disease who underwent surgery and adjuvant systemic treatment (CTx and HT). Clinicopathologic factors, change in pattern of treatment over time, and OS for each treatment option were analyzed. Results: A total of 40,938 women were included in the study; 20,880 (51.0%) received CTx + HT, while 20,058 (49.0%) received HT only. In recent years, there has been a steady increase in the use of HT alone, from 21.0% (2000) to 64.6% (2018). In Cox regression analysis, age, type of breast and axillary operations, T and N stages, body mass index, histologic grade, and presence of lymphovascular invasion were prognostic indicators for OS. There was no significant difference between CTx + HT and HT alone in terms of OS (P = 0.126). Conclusion: Over the years, there has been a shift from CTx + HT to HT alone without a significant difference in OS. Therefore, HT alone could be a safe treatment option in selected patients, even those with T2N1 disease.
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PURPOSE: This study was performed to identify the risk of mortality in patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive ductal carcinoma in situ (DCIS). METHODS: We selected 2,592 patients with HER2-positive DCIS from Korean Breast Cancer Society (KBCS) database between January 1997 and December 2019. Patients who received neoadjuvant chemotherapy were excluded. Logistic regression analysis was used to determine the association between clinical factors and overall death after adjusting for tumor and clinical characteristics. Mortality data were modified using the Statistics Korea data. RESULTS: Thirty deaths (1.2%) were identified out of 2,592 patients in the KBCS database. In the univariate logistic regression analysis, older age, higher body mass index (BMI), type of breast surgery (mastectomy), estrogen receptor-negative, progesterone receptor-negative, and exposure to endocrine therapy were significant clinical factors associated with death. In the multivariate analysis, age (hazard ratio [HR], 1.062; 95% confidence interval [CI], 1.015-1.111; P = 0.006), BMI (HR, 1.179; 95% CI, 1.032-1.347, P = 0.016), breast surgery type (mastectomy vs. lumpectomy; HR, 0.285; 95% CI, 0.096-0.844; P = 0.024), and endocrine therapy (HR, 0.314; 95% CI, 0.099-0.995; P = 0.049) were significant risk factors for mortality. CONCLUSION: Advanced age, higher BMI, mastectomy, and the absence of endocrine therapy were factors associated with poor survival of patients with HER2-positive DCIS. This finding requires further validation combined with additional analysis of large databases.
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Immune checkpoint inhibitors (ICI) have demonstrated efficacy in the treatment of solid cancers. However, there is no unified predictive biomarker available for ICIs. We aimed to compare the prognostic impact of using three PD-L1 antibodies (SP142, SP263, and 22C3) for immunohistochemical (IHC) analysis. We retrospectively investigated tumor tissues derived from 316 breast cancer cases, by constructing tissue microarrays and by performing IHC staining. The immune-cell expression rate (for SP142 and SP263) and combined proportional score (for 22C3) were evaluated, and survival outcomes were analyzed. Prediction models were developed, and values of Harrel's c-index and areas under curves were calculated to compare the discriminatory power. Negative PD-L1 expression based on the 22C3-IHC assay was determined to be an independent prognostic marker for recurrence-free survival (RFS, P = 0.0337) and distant metastasis-free survival (DMFS, P = 0.0131). However, PD-L1 expression based on SP142- and SP263-IHC assays did not reveal a prognostic impact. Among the three antibodies, adding PD-L1 expression data obtained via 22C3-IHC assay to the null model led to a significant improvement in the discriminatory power of RFS and DMFS. We suggest that PD-L1 expression based on the 22C3-IHC assay is a superior prognostic marker than that based on SP142- and SP263-IHC assays.
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Antígeno B7-H1/metabolismo , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais , Antígeno B7-H1/genética , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica/métodos , Mastectomia , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Período Pós-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Análise Serial de TecidosRESUMO
The purpose of this study is to investigate imaging characteristics of young age breast cancer (YABC) focusing on correlation with pathologic factors and association with disease recurrence. From January 2017 to December 2019, patients under 40 years old who were diagnosed as breast cancer were enrolled in this study. Morphologic analysis of tumor and multiple quantitative parameters were obtained from pre-treatment dynamic contrast enhanced breast magnetic resonance imaging (DCE-MRI). Tumor-stroma ratio (TSR), microvessel density (MVD) and endothelial Notch 1 (EC Notch 1) were investigated for correlation with imaging parameters. In addition, recurrence associated factors were assessed using both clinico-pathologic factors and imaging parameters. A total of 53 patients were enrolled. Several imaging parameters derived from apparent diffusion coefficient (ADC) histogram showed negative correlation with TSR; and there was negative correlation between MVD and Ve in perfusion analysis. There were nine cases of recurrences with median interval of 16 months. Triple negative subtype and low CD34 MVD positivity in Notch 1 hotspots showed significant association with tumor recurrence. Texture parameters reflecting tumor sphericity and homogeneity were also associated with disease recurrence. In conclusion, several quantitative MRI parameters can be used as imaging biomarkers for tumor microenvironment and can predict disease recurrence in YABC.
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Neoplasias da Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Receptor Notch1/metabolismo , Adulto , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Meios de Contraste , Feminino , Humanos , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: There is no proven primary preventive strategy for doxorubicin-induced subclinical cardiotoxicity (DISC), especially among patients without a cardiovascular (CV) risk. We investigated the primary preventive effect on DISC of the concomitant use of angiotensin receptor blockers (ARBs) or beta-blockers (BBs), especially among breast cancer patients without a CV risk. METHODS: A total of 385 patients who were scheduled for doxorubicin chemotherapy were screened. Among them, 195 patients of the study populations were included and were randomly divided into two groups [candesartan 4 mg q.d. vs. carvedilol 3.125 mg q.d.] and patients who were unwilling to take one of the medications were evaluated as controls. The primary outcomes were the incidence of early DISC (DISC developing within 6 months after chemotherapy), and late DISC (DISC developing only at least 12 months after chemotherapy). RESULT: Compared with the control group (8 out of 43 patients (18.6%)), only the candesartan group (4 out of 82 patients (4.9%)) showed a significantly lower incidence of early DISC (p = 0.022). Compared with the control group, the candesartan group demonstrated a significantly reduced decrease in left ventricular ejection fraction (LVEF) throughout the study period [-1.0% vs. -3.00 (p < 0.001) at the first follow-up, -1.10% vs. -3.40(p = 0.009) at the second follow-up]. CONCLUSIONS: Among breast cancer patients without a CV risk treated with doxorubicin-containing chemotherapy, subclinical cardiotoxicity is prevalent and concomitant administration of low-dose candesartan might be effective to prevent an early decrease in LVEF. Further large-scale, randomized controlled trials will be needed to confirm our findings.
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Antibióticos Antineoplásicos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Carvedilol/uso terapêutico , Doxorrubicina/efeitos adversos , Tetrazóis/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Benzimidazóis/administração & dosagem , Compostos de Bifenilo/administração & dosagem , Cardiotoxicidade/epidemiologia , Carvedilol/administração & dosagem , Ciclofosfamida/uso terapêutico , Docetaxel/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Medição de Risco , Volume Sistólico/efeitos dos fármacos , Tetrazóis/administração & dosagem , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
The conjunctiva is a thin mucous membrane of the eye. Pterygium, a commonly appearing disease on the ocular surface, requires surgery to excise the conjunctiva to prevent visual deterioration. Recently, transplantation of the amniotic membrane (AM), which is the innermost membrane of the placenta, has been highlighted as an efficient method to cure conjunctiva defects because of its advantages of no side effects compared to mitomycin C treatment and not leaving additional scars on donor site compared to conjunctival autografting. However, to minimize additional damage to the ocular surface by suturing, AM transplantation (AMT) needs to be simplified by using a less invasive, time-saving method. In this work, a visible light-curable protein bioadhesive (named FixLight) for efficient sutureless AMT is applied. FixLight, which is based on bioengineered mussel adhesive protein (MAP), is easily applied between damaged ocular surfaces and transplanted AM, and rapidly cured by harmless blue light activation. Through in vivo evaluation using a rabbit model, the authors demonstrated that FixLight enabled facile, fast, and strong attachment of AM on sclera and promoted ocular surface reconstruction with good biocompatibility. Thus, FixLight can be successfully used as a promising clinical bioadhesive in opthalmological surgeries that require sutureless and rapid operation.