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Introduction: SB3 is a trastuzumab biosimilar approved in Australia, Brazil, Canada, the European Union, the Republic of Korea, Switzerland, and the USA. This real-world study evaluated safety and effectiveness of SB3 as part of the Korean post approval safety management system., Methods: This post-marketing surveillance in Korea included patients in line with approved indications, i.e., patients with early or metastatic breast cancer or metastatic gastric cancer. Safety outcomes were adverse events (AEs) and adverse drug reactions. Effectiveness outcomes were tumor response and event-free survival., Results: 424 patients were evaluated: 366 patients (86%) with early breast cancer, 53 patients (13%) with metastatic breast cancer, and 5 patients (1%) with metastatic gastric cancer. Among patients with breast cancer, AEs (mostly mild) and adverse drug reactions were reported by 158 (37.7%) and 57 (13.6%) patients, respectively. Most patients with an AE (141, 89.2%) had no change in treatment schedule. Treatment was temporarily suspended in 14 (8.9%) patients with an AE and completely discontinued in 7 (4.4%). Among patients with early and metastatic breast cancer who were evaluated for efficacy, objective response rates were 82.7% and 38.3%, respectively. Pathological complete response was 64.6% in patients with early breast cancer., Discussion/conclusion: Safety and efficacy of SB3 demonstrated in this real-world study were comparable with previous studies of reference trastuzumab., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Purpose: Microinvasive breast cancer (MIBC) is an invasive carcinoma with a tumor dimension not exceeding 1 mm. Owing to its low incidence, the rate of axillary node metastasis and its management are not well established. The aim of this study was to assess the incidence of lymph node metastasis (LNM) and identify variables associated with LNM, as well as to evaluate the need for axillary staging in MIBC patients by analyzing nationwide data., Methods: The Korean Breast Cancer Society registry was searched to identify MIBC patients diagnosed between January 1996 and April 2020. Patients without neoadjuvant chemotherapy experiences, systemic metastasis, and missing or discordant data were eligible for the analysis. The incidence rate of LNM was determined, and variables associated with LNM were identified by multivariable regression analysis., Results: Of 2,427 MIBC patients identified, 98 (4.0%) had LNM and 12 (0.5%) had N2/3 disease. Type of breast operation (odds ratio [OR], 2.093; 95% confidence interval [CI], 1.332-3.290; P = 0.001), age (OR, 2.091; 95% CI, 1.326-3.298; P = 0.002), hormone receptor status (OR, 2.220; 95% CI, 1.372-3.594; P = 0.001), and lymphovascular invasion (OR, 11.143; 95% CI, 6.354-19.540; P < 0.001) were significantly related to LNM., Conclusion: The incidence of LNM in MIBC patients was only 4.0% in our study, suggesting that de-escalation of axillary surgical interventions could be carefully considered. The indications for axillary staging should be individualized considering tumor volume, age, hormone receptor status, and lymphovascular invasion to improve the quality of life of MIBC survivors., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2022, the Korean Surgical Society.)

Breast reconstruction during breast-conserving surgery (BCS) can improve the breast shape. This study introduces breast reconstruction in BCS with two types of acellular dermal matrix (ADM). The study included 134 patients who underwent BCS due to breast cancer from February 2018 to May 2021. This study was conducted by one surgeon, and is the result of a three-year study. The patient group who underwent BCS using ADM was mainly targeted at patients with minor to severe defects after the operation. The average age of the patients was 51.8 years, and the body mass index (BMI) was 23.8 kg/m. The specimen weight was 30-120 g. The average surgical time, including reconstruction, was 100.4 min, combined with reconstruction. There were minor complications in six patients. The advantage of using ADM is that it can quickly correct the shape of the breast after conventional BCS surgery. Pellet-type ADM, rather than sheet-type, can create a breast shape similar to that before surgery. Breast reconstruction using ADM can be an easy and convenient method for making a better shape from BCS.

Background: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy., Methods: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot., Results: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK., Conclusion: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Korea is no longer safe from the risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL); the first reported case was a Korean woman in her 40s who had a 7-year-history of receiving an implant-based augmentation mammaplasty using a textured implant. We conducted this study to discuss the emerging crisis of stakeholders in implant-based augmentation mammaplasty and to propose a multi-disciplinary approach to early detection of its complications., Methods: We analyzed medical examination data that was collected from patients who visited us between August 12 and September 27, 2019. We evaluated a total of 114 women (n = 114) in the current study. They were evaluated for whether they were in healthy condition. Moreover, their baseline characteristics were also examined; these included age, gender, height (cm), weight (kg), duration since surgery (years), possession of a breast implant card, the site of surgical incision, side of symptoms and reasons for outpatient visit. Furthermore, the patients were also evaluated for their subjective awareness of the manufacturer, surface and shape of the breast implant. Potential complications include malrotation, folding, seroma, capsule thickening, upside-down rotation, rupture, capsule mass and breast mass., Results: A majority of the patients had a past history of receiving textured implants. The corresponding percentage was 78.95% (90/114) and 85.09% (97/114) based on their subjective awareness of a breast implant and sonographic findings, respectively. That is, it was slightly increased with the use of a breast ultrasound., Conclusion: Here, we propose the following approaches. First, patient data should be prospectively collected. By tracking outcomes and complications of an implant-based augmentation mammaplasty, both high-quality care and patient safety can be ensured. Second, stakeholders in implant-based augmentation mammaplasty should collaborate with customers and regulatory authorities. Third, surgeons should consider applying imaging modalities for early detection of postoperative complications., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Purpose: The purpose of this study was to investigate the displacement of surgical clips in the excision cavity during whole breast irradiation following breast-conserving surgery (BCS) with or without acellular dermal matrix (ADM) insertion, and to analyze clinicopathologic factors associated with the displacement of surgical clips., Materials and Methods: From 2016 to 2017, 100 consecutive breast cancer patients who underwent BCS with the placement of surgical clips (superior, inferior, medial, lateral, and deep sides) in the tumor bed were included in this study. All patients took first planning computed tomography (CT) scan (CT 1) before whole breast irradiation and second CT scan (CT 2) before boost irradiation. Between two sets of planning CT, the displacement of surgical clips was calculated from the ΔX (lateral-medial), ΔY (anterior-posterior), ΔZ (superior-inferior), and three-dimensional (3D) directions. Patients were divided into two groups according to the breast volume replacement with ADM: group A with ADM and group B without ADM., Results: The means and 1 standard deviations of 3D displacement for superior, inferior, medial, lateral and deep clips were 5.2±2.9, 5.2±3.2, 5.6±4.5, 5.6±4.3, and 4.9±4.9 mm in entire cohort (n=100); 5.6±2.6, 6.0±3.5, 6.7±5.8, 6.7±5.7, and 6.1±7.4 mm in group A (n=38); 4.9±3.1, 4.8±3.0, 5.0±3.5, 5.0±2.9, and 4.3±2.8 mm in group B (n=62), respectively. The 3D displacements of group A were longer than those of group B, but only significant difference was observed in lateral clip (p=0.047)., Conclusion: This study demonstrated displacement of surgical clips during whole breast irradiation in patients with ADM insertion. For patients who had breast volume replacement using ADM, adaptive boost planning should be considered.

The clinical significance of physiologic Fluorine-18-fluorodeoxyglucose ( 18 F-FDG) intestinal uptake (IU) based on the predicted link with gut microbiota dysbiosis and inflammatory cytokine production was investigated in a cohort of breast cancer patients. A total of 114 patients were visually classified into the lower or higher IU group. The maximum and mean standardized uptake values of total bowel (TB SUV max and TB SUV mean ) were measured. The gut microbial abundance of the Citrobacter genus of the Enterobacteriaceae family showed a significant positive correlation with TB SUV max and TB SUV mean (q = 0.021 and q = 0.010). The unclassified Ruminococcaceae showed a significant negative correlation with TB SUV max (q = 0.010). The level of tumor necrosis factor alpha (TNF-α) was significantly increased in the high IU group (p = 0.017). The TNF-α levels showed a significant positive correlation with TB SUV max (rho = 0.220 and p = 0.018) and TB SUV mean (rho = 0.250 and p = 0.007). Therefore, our findings suggest that the physiologic intestinal uptake may reflect subclinical inflammation and differences in the composition of the gut microbiome in breast cancer patients.

Background: Although BRCA1 or BRCA2 (BRCA1/2) genetic testing plays an important role in determining treatment modalities in patients with hereditary breast and ovarian cancer, sequence variants with unknown clinical significance or variant of uncertain significance (VUS) have limited use in medical decision-making. With vast quantities of gene-related data being updated, the clinical significance of VUS may change over time. We reinterpreted the sequence variant previously reported as BRCA1/2 VUS results in patients with breast or ovarian cancer and assessed whether the clinical significance of VUS was changed., Methods: We retrospectively reviewed medical records of 423 breast or ovarian cancer patients who underwent BRCA1/2 genetic testing from 2010 to 2017. The VUSs in BRCA1/2 were reanalyzed using the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology standards and guidelines (ACMG/AMP 2015 guidelines) and the VUS was reclassified into five categories: "pathogenic", "likely pathogenic", "VUS", "likely benign", and "benign"., Results: A total of 75 patients (48 sequence types of VUS) were identified as carrying either one or more VUS in BRCA1/2. Among the 75 patients, two patients (2.7%) were reclassified as "likely pathogenic", 30 patients (40.0%) were reclassified as either "benign" or "likely benign", and the remaining 43 patients (57.3%) were still classified as VUS category., Conclusions: Since the clinical significance of VUS in BRCA1/2 may vary from time to time, reinterpretation of the VUS results could contribute to clinical decision-making.

Purpose: Routine supplementation of high-dose calcium significantly decreased the risk of postoperative symptomatic hypocalcemia after thyroidectomy. However, there is an ongoing debate about whether the same results can be achieved with low-dose calcium supplementation., Methods: Patients (n = 138) who underwent total thyroidectomy for thyroid cancer were 1:1 randomly assigned to receive oral supplements of 1,500 mg/day elemental calcium and 1,000 IU/day cholecalciferol for 2 weeks or no supplementation. Primary objective was to compare the incidence of symptomatic hypocalcemia for 3 days after total thyroidectomy. Secondary objective was to find the predictors for postoperative hypocalcemia in patients with thyroid cancer., Results: Sixty-five patients in the calcium group and 69 patients in the control group were finally analyzed. The incidence of symptomatic hypocalcemia showed no difference between the calcium and control group (32.3% vs. 21.7%, P = 0.168). The total dosage of intravenous calcium (593.4 ± 267.1 mg vs. 731.6 ± 622.7 mg, P = 0.430) administered to patients with symptomatic hypocalcemia was also comparable between groups. In a multivariate analysis, parathyroid hormone level of 13 pg/mL at postoperative day 1 was only predictive for symptomatic hypocalcemia, and its incidence was 20.9 times (95% confidence interval, 6.8-64.5) higher in patients with parathyroid hormone <13 pg/mL. Other factors did not predict the development of hypocalcemia, including clinicopathological features and routine supplementation of low-dose calcium., Conclusion: Routine low-dose calcium supplementation did not reduce the risk of postoperative hypocalcemia. Patients who may benefit from calcium supplementation should be carefully selected., Competing Interests: CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.

With the increased utilization of robot thyroidectomy in recent years, surgical proficiency is the paramount consideration. However, there is no single perfect or ideal method for measuring surgical proficiency. In this study, we evaluated the learning curve of robotic thyroidectomy using various parameters. A total of 172 robotic total thyroidectomies were performed by a single surgeon between March 2014 and February 2018. Cumulative summation analysis revealed that it took 50 cases for the surgeon to significantly improve the operation time. Mean operation time was significantly shorter in the group that included the 51st to the 172nd case, than in the group that included only the first 50 cases (132.8 ± 27.7 min vs. 166.9 ± 29.5 min; p < 0.001). On the other hand, the surgeon was competent after the 75th case when postoperative transient hypoparathyroidism was used as the outcome measure. The incidence of hypoparathyroidism gradually decreased from 52.0%, for the first 75 cases, to 40.2% after the 76th case. These results indicated that the criteria used to assess proficiency greatly influenced the interpretation of the learning curve. Incorporation of the operation time, complications, and oncologic outcomes should be considered in learning curve assessment., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Purpose: Dendritic cells (DC) are a class of bone marrow-derived cells found in the blood, epithelia, and lymphoid tissues, and are the most efficient antigen presenting cells. The number and function of DC can change dramatically in cancer patients. The aim of this study is to correlate the levels of circulating DC subsets with clinical characteristics in breast cancer patients., Methods: Peripheral blood samples were collected from 53 untreated breast cancer patients before surgery between January 2013 and November 2013. Forty-one healthy, age-matched volunteers served as the control group. The phenotypes of circulating plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were determined using fluorescence activated cell sorting assays. Correlations between DCs immunophenotypes and clinicopathologic characteristics of these breast cancer patients were then determined., Results: Patients with breast cancer had higher levels of pDCs ( p = 0.046). No relationships were observed with tumor stage and intrinsic subtype. Estrogen receptor (ER) positive patients had higher levels of mDCs than ER negative patients ( p = 0.025) and human epidermal growth factor receptor 2 (HER-2) positive patients had higher levels of pDCs than HER-2 ( p = 0.040). No relationships were observed with T stage, N stage, Ki67 index, histologic grade, nuclear grade, and lymphovascular invasion. In multiple regression analysis, patients with HER-2 positive breast cancer had higher levels of pDCs than HER-2 negative patients ( p = 0.026)., Conclusion: An increase of pDCs in the peripheral blood of breast cancer patients was observed and patients with HER-2 positive breast cancer had higher levels of circulating pDCs than did HER-2 negative patients. Our results suggest that expression of DCs can differ according to breast cancer subtype and indicate that, with further investigation, DC expression has the possibility of being presented as a prognostic factor., Competing Interests: Conflict of Interest: The authors declare that they have no competing interests.

Background: The effect of Graves' disease on the risk of postoperative complications in patients undergoing total thyroidectomy is unclear., Methods: The incidence of recurrent laryngeal nerve (RLN) injury and hypoparathyroidism were analyzed between 165 patients with Graves' disease (GD group) and 1:1 matched patients with euthyroid states (control group)., Results: The matched cohorts did not differ in age, sex, body mass index, pathologic diagnosis, and extent of operation. Excised thyroid weight was higher in the Graves' disease than in the control group (60.1 g vs 22.6 g; P < .001). Multivariate analysis showed that Graves' disease significantly increased risks of transient RLN injury (odds ratio [OR] = 4.7, 95% confidence interval [CI] = 1.5-15.5; P = .010) and transient hypoparathyroidism (OR = 2.8, 95% CI = 1.3-5.8; P = .007). Rates of permanent complications were comparable in the Graves' disease and control groups., Conclusions: Graves' disease can be a predictive factor for postoperative RLN injury and hypoparathyroidism after total thyroidectomy., (© 2018 Wiley Periodicals, Inc.)

Regarding TNM staging in breast cancer, T2 category is currently not divided into subcategories even though it covers a wider range of tumor sizes than T1 category. Using Korean Breast Cancer Registry database, data of 41 071 women diagnosed as non-metastatic T2 breast cancer between 2001 and 2014 were analyzed. Cutoff value for optimal tumor size was approximated by receiver operating characteristic (ROC) curve to subcategorize T2 tumors. Overall survival (OS) was compared between two subcategories. Median follow-up period was 65 months. Of 41 071 patients, 4504 (11.0%) died. Based on ROC curve analysis, 3.0 cm was selected as the cutoff value. Five-year OS rate was 91% in patients with breast tumors ≤3.0 cm (T2a) and 86% in patients with breast tumors >3.0 cm (T2b) (log-rank P < 0.001). T2b subcategory showed worse OS than T2a subcategory regardless of node status (log-rank P < 0.001 for all node categories). Within every subgroup defined by primary OS analysis covariates, T2b subcategory consistently showed worse outcome compared to T2a subcategory. By multivariate analysis, T2b subcategory was a significant independent prognostic factor of OS (hazard ratio: 1.26, 95% CI = 1.18-1.34). T2 category of breast cancer could be subcategorized into T2a and T2b with a cutoff value of 3 cm. These subcategories definitely showed different OSs even after adjusted for known prognostic factors. Subcategorization of T2 category might be useful for predicting prognosis more accurately and tailoring adjuvant therapy., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Clinical pathways have been proposed as a way to improve organizational efficiency and maximize patient outcomes. However, little is known as to whether a clinical pathway is effective for thyroid cancer., Methods: The study subjects included 216 patients who were managed after clinical pathway implementation and 145 control patients. Length of stay, cost per patient, and nurses' satisfaction were compared in the 2 groups., Results: Mean length of stay was 0.8 days shorter in the clinical pathway group than in the control group (2.9 vs 3.7 days; P = .023). Cost per patient was also lower in the clinical pathway than in the control group (USD $3953.00 vs USD $4636.00; P < .001). Nurses' overall satisfaction scores improved from 71.6% before to 82.5% after implementation of the clinical pathway and their job characteristics scores increased from 61.1% to 75.0%., Conclusion: Implementation of a clinical pathway for thyroid cancer can improve nurses' satisfaction with reduction of hospital stay and costs., (© 2018 Wiley Periodicals, Inc.)

Background/aim: We evaluated dosimetric and clinical results of volumetric-modulated arc therapy (VMAT) treating internal mammary nodes (IMNs) in patients with locally advanced breast cancer., Patients and Methods: Between July 2012 and December 2013, treatment outcomes of 31 patients with stage III breast cancer treated with postoperative radiotherapy including the IMN field using VMAT were analyzed., Results: The median follow-up was 25.2 months. VMAT showed good homogeneity and improved conformity. The incidence of lung toxicity of grade 2 or more was 3.2%, and cardiac toxicity was not observed. No patient developed local recurrence., Conclusion: VMAT appears safe for the treatment of locally advanced breast cancer including the IMN field., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer., Methods/design: Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively., Discussion: This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer., Trial Registration: ClinicalTrials.gov Identifier NCT01589367.

The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.

Purpose: Breast cancer is one of the most frequent malignancies in Korean women, and its incidence is increasing at a rapid rate. Since 1996, the Korean Breast Cancer Society has collected nationwide breast cancer data using an online registration program and analyzed the data biennial. The purpose of this study was to evaluate the characteristics of Korean breast cancer and to analyze changes in these characteristics over the period of time., Methods: Data were collected from 41 medical schools (74 hospitals), 24 general hospitals, and 6 private clinics. Data on the total number, gender, and age of newly-diagnosed breast cancer patients were collected through a questionnaire. Additional data were collected and analyzed from the online database., Results: In 2010, 16,398 patients in Korea were newly diagnosed with breast cancer. The crude incidence rate of female breast cancer was 67.2 cases per 100,000, and the median age at diagnosis was 49 years. The incidence of breast cancer was highest in patients aged between 40 and 49 years. Since 1996, there has been a significant increase in the proportion of early-stage cancers (detected in stage 1 or 2), the percentage of estrogen receptor-positive cancers, and in the proportion of patients receiving breast-conserving surgery., Conclusion: The incidence and clinical characteristics of Korean breast cancer are slowly changing to the patterns of Western countries. To understand changing patterns in the characteristics of Korean breast cancer, the nationwide data should be continuously analyzed.

Purpose: A chemotherapy response assay test is performed to evaluate the degree of tumor growth inhibition by a chemotherapeutic agent. Several studies have been done on its usefulness; however, to the best of our knowledge, only a few studies concerning the relationship between chemotherapy response assay test results and breast cancer patients' prognoses have been conducted. Thus, we performed this study to analyze this relationship., Methods: Among breast cancer patients who underwent curative surgery and neoadjuvant or adjuvant chemotherapy between August 2004 and December 2009, 102 were enrolled in this study. Chemotherapeutic regimens for patients were doxorubicin plus taxane or doxorubicin plus cyclophosphamide followed by taxane. We divided these patients into two groups (sensitive group [n=19] and resistant group [n=83]) and analyzed the relationship between chemosensitivity results and patient prognosis., Results: The sensitive group was associated with poor disease-free survival (DFS) (p=0.003) and overall survival (OS) (p<0.001). No significant differences were observed in tumor histology (p=0.548), tumor size (p=0.479), number of metastatic lymph nodes (p=0.326), histologic grade (p=0.077), or nuclear grade (p=0.216) between the two groups. However, in respect to molecular subtype, the HER2-positive type and triple negative breast cancer were more frequently observed in the sensitive group (p=0.001). In a univariate and multivariate analysis for DFS, doxorubicin sensitivity was significantly associated with a poor prognosis (p<0.05)., Conclusion: Better chemosensitivity results are associated with a poor prognosis in breast cancer patients who have undergone anthracycline- and taxane-based chemotherapy, however, examination of additional cases and the use of a longer study period are needed.

Context: In Korea, where PTC comprises about 90-95% of the reported thyroid cancers, the prevalence of BRAF(V600E) mutation in papillary thyroid carcinoma (PTC) is above 80%., Objective: We analyzed the surgical result according to a management guideline based on the BRAF(V600E) mutation status of thyroid nodules., Design: A total of 865 thyroid nodules were prospectively analyzed for their cytology and BRAF(V600E) mutation status by pyrosequencing. For the patients who had a diagnosis of atypical cells of undetermined significance (ACUS), we recommended surgery when there was positivity for BRAF(V600E) mutation or the nodules were clinically suspicious., Results: Among 865 cases, 504, 141, 54, 140, 10, and 16 were diagnosed as benign, ACUS, suspicious for malignancy, malignant, suspicious for follicular neoplasm, and nondiagnostic, respectively. None of the 504 benign, 45 (31.9%) of the 141 ACUS, 46 (85.2%) of the 54 suspicious for malignancy, 129 (92.1%) of the 140 malignant, and one (10%) of the 10 suspicious for follicular neoplasm cases showed BRAF(V600E) mutation. Surgery was recommended to all 45 patients with BRAF(V600E) mutation-positive ACUS nodules; among them, 30 patients underwent surgery, 29 had PTC, and one had nodular hyperplasia. All the patients diagnosed as suspicious for malignancy or malignant were advised to undergo an operation, and they turned out to have PTCs regardless of their BRAF(V600E) mutation status., Conclusions: We found that performing BRAF(V600E) mutation analysis on the fine-needle aspiration biopsy specimens was of great help to make a therapeutic decision for thyroid nodules when the fine-needle aspiration biopsy results were equivocal.

Unlabelled: A mini-symposium was held in Montreal, Canada, at the International Surgical Week for the Breast Surgical International in 2007 addressing the question whether breast cancer is the same disease in Asian and Western countries. Numerous investigators from Asian and Western countries presented the epidemiologic and clinical outcome data of women with breast cancer. Although there are significant similarities, the striking difference is that the peak age for breast cancer is between 40 and 50 years in the Asian countries, whereas the peak age in the Western countries is between 60 and 70 years. Also, the incidence of breast cancer in Asia is rising and is associated with increased mortality. In the West, although the incidence is increasing, the mortality rate is definitely decreasing. Future prospective data collection from Asian and Western countries may provide further interesting epidemiologic and outcome data regarding the outcome of women with breast cancer from Asian and Western countries., Background: Whether breast cancer is the same disease in Asian and Western countries was the topic of a 2007 Breast Surgery International symposium at International Surgical Week., Methods: Participating investigators from China, Taiwan, India, Japan, South Korea, Sweden, Canada, and the United States were asked beforehand to provide data on the epidemiology and treatment outcome of women in their countries., Results: Comparisons of the epidemiologic and clinical outcome data of women with breast cancer showed significant similarities, but the striking difference is that the peak age is between 40 and 50 years in Asian countries, but is between 60 and 70 years in Western countries. The incidence of breast cancer in Asia is rising and is associated with increased mortality. In the West, although the incidence is also increasing, the mortality rate is definitely decreasing., Discussion: Future prospective data collection from Asian and Western countries may provide further interesting epidemiologic and outcome data regarding the outcome of women with breast cancer from Asian and Western countries.

Aims: Rapamycin and its analogues are currently being tested in clinical trials as novel-targeted anticancer agents. Pre-clinical studies that used breast cancer cell lines have suggested that p-Akt or p-S6K1 expressing tumors, as well as PTEN negative tumors, were sensitive to rapamycin. The aims of this study were to determine the proportion of breast cancer that could be candidates for rapamycin treatment and to elucidate the clinicopathologic characteristics and prognosis of potentially rapamycin-sensitive tumors., Methods: We evaluated the expressions of PTEN, p-Akt and p-S6K1 by performing immunohistochemistry in 122 breast cancer tissues. We analyzed the association of the expression of these proteins with the cliniopathologic variables and the disease-free survival., Results: PTEN negative tumors, p-Akt expressing tumors and p-S6K1 expressing tumors constituted 4.1% (5/122), 41.0% (50/122), and 36.1% (44/122) of the total tumors, respectively. The proportion of tumors that met the criteria of rapamycin sensitivity was 54.9% (67/122). We could not find any significant correlation between the expression of these proteins and the other prognostic factors. However, the prognosis of tumors with a p-S6K1 expression was significantly worse than that of the p-S6K1 negative tumors., Conclusion: Based on the status of the PTEN, p-Akt and p-S6K1 expressions as predictors of rapamycin sensitivity, this study suggested that over 50% of breast cancer patients could be potential candidates for rapamycin treatment. In addition, the p-S6K1 expression may constitute an independent prognostic factor for disease-free survival.

Purpose: The aim of this study was to evaluate health-related quality of life (HRQOL) in breast cancer patients across countries, and to cross-culturally examine the impact of psychosocial factors on HRQOL., Patients and Methods: A total of 413 women with breast cancer from Germany (n = 195), Japan (n = 112), and Korea (n = 106) completed a survey assessing HRQOL and HRQOL-related factors. HRQOL was measured using the Short-Form Health Survey (SF-8). Measures of psychological distress (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised), coping (Dealing with Illness Inventory-German Revised), and social support (Illness-Specific Social Support Scale-German Revised) were included., Results: The effect of the factor country on physical QOL was seen to be significant, but small (P = 0.049, ES = 0.018). The scales of General Health (P = 0.023), Vitality (P = 0.004), and Role Emotional (P = 0.003) differed across countries, with the South Korean patients having lower scores compared to the German and Japanese patients. The nature of the impact of psychosocial factors on HRQOL did not differ greatly across countries except with regard to avoidance, however, the degree to which these factors influence HRQOL did differ greatly. Overall, depression, depressive coping, and problematic support showed a strong detrimental effect on the HRQOL of breast cancer patients., Conclusions: Results from this study suggest that strategies which target an improvement of HRQOL in cancer patients should also consider the patients' cultural and healthcare system contexts. Interventions are needed to improve detrimental psychosocial factors.

Background: This multicenter phase II study was conducted to evaluate the response and safety of a combination of docetaxel plus doxorubicin as neoadjuvant therapy for stage II, III breast cancer., Methods: Patients with stage II or III breast cancer underwent three cycles of neoadjuvant chemotherapy with doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 every 3 weeks followed by curative surgery. Prophylactic GCSF was not used., Results: Ninety patients were enrolled in the study and 86 were evaluable for efficacy. The median age was 43 years (range, 30-69). The mean relative dose intensity was 0.98 for docetaxel and 0.98 for doxorubicin. Breast-conserving surgery was performed in 12 (13.7%) patients. The clinical overall response rate was 86% and pathologic complete response was 10.5%. Grade 3/4 neutropenia was observed in 26% of total 258 cycles and febrile neutropenia was observed in 15.8%. Pneumonia was observed in one patient and grade 3 mucositis was observed in three patients., Conclusion: Docetaxel and doxorubicin was an effective and well-tolerated neoadjuvant chemotherapy for stage II and III breast cancer. Clinical benefit of this treatment will be confirmed by survival data with long term follow up.

The aims of study were to compare the rates of ipsilateral breast tumor recurrence (IBTR), for patients treated with either quadrantectomy or lumpectomy at a single institution, and to identify predictors of IBTR after breast-conserving therapy (BCT). The database and medical records of 807 patients who underwent BCT for breast cancer between 1987 and 2002 were reviewed. The age of the patient, tumor size, lymph node status, extensive intraductal component (EIC), re-excision, final margin status, and the extent of surgery were examined in reference to IBTR rates. Of the total 807 patients, 456 (56.5%) had undergone quadrantectomy and 351 patients (43.5%) had lumpectomy. Apart from the higher re-excision rate in the lumpectomy group (p < 0.001), there were no significant differences in clinical and pathologic characteristics between the patients in the two groups. At the median follow-up time of 72 months, 28 cases of IBTR (3.4%) and 56 cases of systemic recurrence (6.9%) had developed in 72 patients (8.9%). On multivariate analysis, young age (< or =35) (p = 0.041), positive lymph node (p < 0.001), and the presence of EIC (p = 0.004) were independent predictors of IBTR. However, we could not find a significant difference in IBTR rate between the two groups (p = 0.546). Thus, the extent of breast surgery (quadrantectomy or lumpectomy) did not make a significant difference in IBTR if adequate surgical margins could be achieved.

The amplification of cyclin D1, located on chromosome 11q13, in breast cancer patients has been found to be associated with reduced relapse-free and overall survival; however, there still exists strong controversy about these findings. In order to evaluate the prognostic value of cyclin D1 and other prognostic variables in human breast cancers, we have assessed estrogen receptor (ER) status, cyclin D1, c-erbB2 and p53 overexpression in 175 primary breast carcinomas, and investigated the relationships of prognostic variables to the patient clinical outcome and the association between cyclin D1 overexpression and other prognostic variables. There was some degree of variability in staining intensities and proportions within the same tumor. The overexpression of both cyclin D1 and ER revealed a significantly prolonged survival in univariate analysis (P = 0.020). Among the various prognostic variables, distant metastasis showed a statistically significant association with overall survival. A significant correlation was observed between cyclin D1 overexpression and small size of the primary tumor (P = 0.031), low Bloom and Richardson's histological grade (P = 0.001), and positive ER status (P = 0.000). In contrast to what was previously expected, the present study suggests that the overexpression of cyclin D1 has a tendency to have a positive clinical outcome and a potential role in identifying a subset of patients predicting a good prognosis, particularly when ER is coexpressed.