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Phyllodes tumor (PT) is a rare fibroepithelial neoplasm of the breast. The proper extent of resection is still under debate. This study aimed to investigate the optimal surgical margin to prevent recurrence after surgery for PT and to evaluate risk factors for local recurrence (LR).Retrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for PT at Seoul National University Bundang Hospital between July 2003 and February 2022 were reviewed.Of the 439 patients included, 285 were benign, 129 were borderline, and 25 were malignant. There was no statistically significant difference in 5-year disease-free survival (DFS) between margin-negative and margin-involved patients (87.3% vs. 85.1%, p = 0.081). When patients were classified into groups, according to margin status, as conventional (≥ 1 cm from tumor), close ( 1 cm from tumor), or involved, 5-year DFS rates were also similar (100% vs. 86.9% vs. 85.1%, p = 0.170). In subgroup analysis for different histologic grades, 5-year DFS was not affected by margin involvement. In univariate analysis, large tumor size ( 5 cm; hazard ratio [HR] 2.857, p = 0.028) and infiltrative tumor border (HR 3.096, p = 0.012) were independent risk factors for LR. Further multivariate analysis found both factors to be prognostic.Recurrence was not significantly influenced by margin status in all histological grades. In benign and borderline tumors, local excision without wide surgical margins could be sufficient, and watchful waiting could be an option for patients with positive margins after initial surgery.

PurposeEstrogen receptor (ER) expression in breast cancer plays an essential role in carcinogenesis and disease progression. Recently, tumors with low level (1-10%) of ER expression have been separately defined as ER Low Positive (ERlow). It is suggested that ERlow tumors might be morphologically and behaviorally different from tumors with high ER expression (ERhigh).MethodsRetrospective analysis of a prospective cohort database was performed. Patients who underwent curative surgery for early breast cancer and had available medical records were included for analysis. Difference in clinicopathological characteristics, endocrine responsiveness and five-year recurrence-free survival was evaluated between different ER subgroups (ERhigh, ERlow, and ER-negative (ER-)).ResultsA total of 2162 breast cancer patients were included in the analysis, Tis and T1 stage. Among them, 1654 (76.5%) were ERhigh, 54 (2.5%) were ERlow, and 454 (21.0%) were ER- patients. ERlow cases were associated with smaller size, higher histologic grade, positive human epidermal growth factor receptor 2 (HER2), negative progesterone receptor, and higher Ki-67 expression. Recurrence rate was highest in ER- tumors and was inversely proportional to ER expression. Recurrence-free survival was not affected by hormonal therapy in the ERlow group (P = 0.418).ConclusionERlow breast cancer showed distinct clinicopathological features. ERlow tumors seemed to have higher recurrence rates compared to ERhigh tumors, and they showed no significant benefit from hormonal therapy. Future large scale prospective studies are necessary to validate the treatment options for ERlow breast cancer.

Backgrounds: The ACOSOG Z0011 trial revealed oncologic outcomes in patients who underwent breast conserving surgery (BCS) and sentinel lymph node biopsy only versus completion axillary dissection to be equivalent. It was also reported that axillary recurrence rate to be not different between axillary dissection group and SLNB only group, despite the positive rate of over 20% in non-sentinel lymph nodes. It led to suspicion that the role of SLNB in local control to be less significant than previously recognized. Currently trials such as SOUND trial and NAUTILUS trial are being conducted in cT1N0 breast cancer undergoing BCS to compare the outcomes between the current standard surgery and no axillary surgery. Purposes: This study aimed to investigate the factors associated with positive SLN in patients with T1 breast cancer, including T substages. We also evaluated the oncologic outcomes according to SLN positivity. Method: We retrospectively reviewed medical records of patients with pT1 breast cancer who underwent BCS including SLNB at Seoul National University Bundang Hospital from 2010 to 2015 (n=986). SLN positive was defined as one or more micro- to macro-metastasis in axillary lymph node specimen. Overall, regional, and systemic recurrence-free survival (RFS, RRFS, SRFS) and overall survival (OS) were estimated by the Kaplan-Meier analysis. Result: Of 986 patients, positive SLN was observed in 116 patients (11.8%). Regarding T substages, T1mic, T1a, and T1b gouprs showed SLN positive rate of 0%, 3.4%, and 8.5% respectively whereas T1c showed 15.3%. Multivariable logistic regression analyses revealed clinical T stage (OR 1.791, 95% CI 1.061-3.023, P=0.029), >C2 finding in preoperative axillary ultrasonograpy (OR 3.021, 95% CI 1.740-5.248, P< 0.001), usual histologic type including invasive ductal carcinoma, invasive lobular carcinoma, and metaplastic carcinoma confirmed in preoperative biopsy (OR 4.406, 95% CI 1.357-14.305, P=0.014) to be independent predictive factors for SLN positivity. The median follow-up period was 103.03 months. The 5 year RFS, RRFS, SRFS, and OS showed no statistical difference between SLN positive group and negative group. In multivariable Cox regression analysis, serum CEA level higher than 5ng/ml at diagnosis (HR 7.534, 95% CI 3.336-17.019, P=0.002) and Ki-67 level higher than 20% (HR 7.534, 95% CI 3.336-17.019, P< 0.001) were shown to be the independent prognostic factors for RFS. Conclusion: Our data implicates that patients with T1c breast cancer should undergo SLNB at all times presently, considering substantially higher SLN positive rate compared to other T1 substages (16.8% vs. 6.1%, P< 0.001) although no survival difference was observed between SLN positive group and negative group. Kaplan-Meier curve of recurrence-free survival and overall survival Kaplan-Meier curve of recurrence-free survival and overall survival Kaplan-Meier analyses revealed no difference of recurrence-free survival, overall survival between SLN-positive and SLN-negative group. Univariable and multivariable model for recurrence-free survival Higher Ki-67 expression, ER negativity, PR negativity, HER2 positivity were shown to be independent risk factors associated with shorter RFS. Multivariable analysis showed higher Ki-67 expression as the sole independent risk factor for shorter RFS. Citation Format: Hyoung Won Koh, Hee-Chul Shin, Eun-Kyu Kim, Eunyoung Kang. Positive sentinel lymph node does not affect prognosis in T1 breast cancer patients who undergo breast conserving surgery with sentinel lymph node biopsy. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-32.

Purpose: Identifying patients who may benefit from neoadjuvant chemotherapy will facilitate personalized treatment regarding chemotherapy and surgery. This study compares the predictive performance of an artificial neural network algorithm with nomogram to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with advanced breast cancer.. Methods: Medical records of 359 patients with advanced breast cancer who received NAC prior to surgical resection between January 2017 and December 2019 were retrospectively reviewed. Random over sampling method was used to overcome data imbalance and random sampling method to divide patients into training and test sets at a split ratio of 7:3. Univariate and multivariate regression analyses were used to develop a nomogram and a machine learning model based on artificial neural network. Performance of the two models were evaluated using the validation sets in terms of area under the receiver operating characteristic curve (AUC).. Results: Multivariate logistic regression analysis showed that high level of estrogen receptor (ER) (OR 0.84, p < 0.001), positive human epidermal growth factor receptor 2 (HER2) status (OR 1.25, p < 0.001), complete response on magnetic resonance imaging (MRI) (OR 1.62, p < 0.001), abnormal CEA level after NAC (OR 0.86, p = 0.051), and abnormal CA15-3 level after NAC (OR 0.87, p = 0.074) were independent predictors of pCR. A nomogram and a neural network model to predict pCR were developed using the five predictors. Validation test showed AUCs of 0.789 [95 % confidence interval (CI), 0.707-0.871] for the nomogram and 0.876 [95 % CI, 0.808-0.943] for the neural network model.. Conclusion: We developed a nomogram and an artificial neural network (ANN)-based machine learning model to predict pCR after NAC. Both models showed excellent performance, but the ANN model performed better in terms of accuracy and discrimination. Machine-learning algorithms hold promise in medical application and provide better prediction than nomogram. Citation Format: Hee-Chul Shin, Ji-Jung Jung, Eun-Kyu Kim, Eunyoung Kang. Development of an aritifical neural network model and comparison with nomogram for prediction of pathological complete response after neoadjuvant chemotherapy in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-06.

Background Mammography screening has been proven to detect breast cancer at an early stage and reduce mortality; however, it has low accuracy in young women or women with dense breasts. Blood-based diagnostic tools may overcome the limitations of mammography. This study assessed the diagnostic performance of a three-protein signature in patients with suspicious breast lesions. Findings This trial (MAST; KCT0004847) was a prospective multicenter observational trial. Three-protein signature values were obtained using serum and plasma from women with suspicious lesions for breast malignancy before tumor biopsy. Additionally, blood samples from women who underwent clear or benign mammography were collected for the assays. Among 642 participants, the sensitivity, specificity, and overall accuracy values of the three-protein signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by the demographic features, clinicopathologic characteristics, and co-morbidities of the participants. Conclusions The present trial showed an accuracy of 70.6% for the three-protein signature. Considering the value of blood-based biomarkers for the early detection of breast malignancies, further evaluation of this proteomic assay is warranted in larger, population-level trials. This Multi-protein Assessment using Serum to deTermine breast lesion malignancy (MAST) was registered at the Clinical Research Information Service of Korea with the identification number of KCT0004847 (https://cris.nih.go.kr).

The relationship between obesity and breast cancer stage is not well-known in the Korean population. This study aimed to identify the effect of body mass index (BMI) on initial breast cancer stage.Among patients who underwent surgery for breast cancer (stages 0-III) from June 2003 to December 2018, we analyzed 4510 patients for whom there were BMI data.The average BMI of our patients was 23.5 (14.2-44.9). In total, 4.6% and 24.2% of the patients had a BMI of ≥30 and 25-29.9, respectively. In the patients with obesity, the proportion of T2 to T4 was 41.4%, which was higher than that in patients with a BMI of 25 to 29 (28.4%; P = .001) or a BMI of25 (23.3%; P.001). There was no difference in positive rates of estrogen receptor and progesterone receptor with BMI, but obese patients were less likely to be human epidermal growth factor receptor 2 positive. Patients with higher stages were more likely to have a higher BMI. The effect of BMI on stage was stronger in patients50 years (odds ratio, 2.439; 95% CI, 1.783-3.335). Although there was no statistical significance, tumors2 cm were less likely to be palpable in obese patients than in patients of normal weight (nonpalpable in 33.8% and 27.0%, respectively).Our study suggests that obesity is associated with a more advanced breast cancer stage, which represents a poor prognosis, and large tumors tend to be less palpable in women with obesity.

Purpose Several predictive models have been developed to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC), but few of them are broadly applicable due to radiologic complexity and institution-specific clinical variables, and none have been externally validated. The purpose of this study was to develop and externally validate a machine learning model that predicts pCR following NAC in breast cancer patients using routinely collected clinical and demographic variables. Methods Electronic medical record data of patients with advanced breast cancer who received NAC prior to surgical resection from January 2017 to December 2020 were reviewed. Patient data from Hospital A was split into training and internal validation cohort. Five machine learning techniques including gradient boosting machine, support vector machine, random forest, decision tree and neural network were used to build predictive models and area under the receiver-operating characteristic curve (AUC) were compared to select the best model. Finally, the model was further validated in an independent cohort from Hospital B. Results A total of 1003 patients were included in the study: 287 in the training cohort, 71 in the internal validation cohort, and 645 in the external validation cohort. Overall, 36.3% of patients achieved pCR. Among the five machine learning models, gradient boosting machine showed the highest AUC for pCR prediction (AUC 0.903, 95% CI 0.833–0.972). External validation confirmed AUC of 0.833 (95% CI 0.800-0.865). Conclusion We used commonly available clinical and demographic variables to develop a machine learning model to predict pCR following NAC. External validation of the model demonstrated good discrimination power, which showed that routinely collected variables are sufficient to build a good prediction model.

Adjuvant endocrine therapy is an integral component of care for hormone-dependent breast cancer. Tamoxifen is a potent inducer of ovarian function and consequent hyperestrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenon remain unclear.Data of patients younger than 60 years who received adjuvant tamoxifen therapy for hormone-dependent breast cancer (stages 0-III) and who underwent regular follow-up of laboratory results for follicle-stimulating hormone and estradiol levels were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinicopathologic factors related to ovarian hyperstimulation.Among 205 patients, 19 (9.3%) showed high values of serum estradiol during tamoxifen therapy. The mean (± SD) serum concentrations of estradiol and follicle-stimulating hormone were 1047.97 ± 638.8 pg/mL and 11.5 ± 7.3 mIU/mL, respectively. A mean of 400.83 days elapsed from the start of the single administration of tamoxifen to the initial detection of a high concentration of estradiol. Univariate and multivariate analyses showed that younger age (40 years) and only endocrine therapy without chemotherapy were significantly related to a higher prevalence of ovarian hyperstimulation (P = .015, relative risk = 7.49 for age 40 years; P = .017, relative risk = 32.9 for no chemotherapy). Pathologic stages and tumor characteristics were not related to the manifestation of ovarian hyperstimulation.Young age (40 years) and endocrine treatment without chemotherapy were risk factors for the incidence of ovarian hyperstimulation during tamoxifen treatment. Close monitoring of endocrine parameters during treatment with tamoxifen especially in this patient group is essential.

PurposeHereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC).Materials and MethodsA total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017.ResultsOf 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1.ConclusionNGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

Identifying breast cancer patients who may benefit from neoadjuvant chemotherapy will facilitate personalized treatment regarding chemotherapy and surgery. In our work, we developed two predictive models, nomogram and a machine learning model based on artificial neural network (ANN), to anticipate pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer. We demonstrated that high level of estrogen receptor (ER) positivity, positive human epidermal growth factor receptor 2 (HER2) status, complete response on magnetic resonance imaging (MRI), abnormal CEA level after NAC, and abnormal CA15-3 level after NAC were significant predictors of pCR. A nomogram and ANN model trained to predict pCR were developed using these five predictors. The performance of the two models were tested using a fully independent test set. Validation test showed the area under the receiver operating characteristic curve (AUC) of 0.789 (95% confidence interval (CI), 0.707-0.871) for the nomogram and 0.876 (95% CI, 0.808-0.943) for the ANN model. Both models showed excellent performance, but the ANN model performed better in terms of accuracy and discrimination. Machine-learning algorithms hold promise in medical application and provide better prediction than nomogram.

Monitoring of patient and tumor during chemotherapy is important to determine whether the chemotherapy is effective to the patient. Variants affect drug enzyme activities and altered enzyme activities can be potential predictors for chemotherapeutic agents including cyclophosphamide and paclitaxel. Response to chemotherapy is primarily based on somatic mutations but germline variants may predict cancer cell sensitivity to chemotherapeutic agents. Furthermore, patient's genetic variation of immune system was reported to be associated with drug response and toxicity. Recently, the somaric and germilne genomic variation influences the pharmacokinetics of chemotherapy and these variation can be biomarkers for chemotherapy.

Monitoring of patient and tumor during chemotherapy is important to determine whether the chemotherapy is effective to the patient. Variants affect drug enzyme activities and altered enzyme activities can be potential predictors for chemotherapeutic agents including cyclophosphamide and paclitaxel. Response to chemotherapy is primarily based on somatic mutations but germline variants may predict cancer cell sensitivity to chemotherapeutic agents. Furthermore, patient's genetic variation of immune system was reported to be associated with drug response and toxicity. Recently, the somaric and germilne genomic variation influences the pharmacokinetics of chemotherapy and these variation can be biomarkers for chemotherapy.

We combined the abbreviated and ultrafast magnetic resonance imaging (MRI) technique with the standard MRI protocol and compared lesion characterization quantitatively and qualitatively to the standard MRI protocol. Fifty-six patients with breast cancer who underwent MRI from June 2017 to May 2018 and fulfilled our inclusion criteria were included. Three radiologists measured the lesion sizes, described the MRI findings using BI-RADS lexicon, and demarcated the regions of interest to extract the volumetric quantitative and semi-quantitative parameters. We used Pearson's correlation analysis comparing the quantitative and semi-quantitative parameters. To evaluate the inter-observer variability, we calculated the intra-correlation coefficient (ICC). We also analysed the correlation in BI-RADS lexicon. There were 45 (80.4%) luminal and 11 (19.6%) non-luminal breast cancers, and the most common tumour subtype was invasive carcinoma (n = 48, 85.7%), followed by ductal carcinoma in situ (n = 8, 14.3%). Regarding correlation between the quantitative and semi-quantitative parameters, Ktrans significantly correlated with the wash-in factor (r, 0.862; P

Autologous reconstruction using abdominal flaps remains the most popular method for breast reconstruction worldwide. We aimed to evaluate a prediction model using machine-learning methods and to determine which factors increase abdominal flap donor site complications with logistic regression. We evaluated the predictive ability of different machine learning packages, reviewing a cohort of breast reconstruction patients who underwent abdominal flaps. We analyzed 13 treatment variables for effects on the abdominal donor site complication rates. To overcome data imbalances, random over sampling example (ROSE) method was used. Data were divided into training and testing sets. Prediction accuracy, sensitivity, specificity, and predictive power (AUC) were measured by applying neuralnet, nnet, and RSNNS machine learning packages. A total of 568 patients were analyzed. The supervised learning package that performed the most effective prediction was neuralnet. Factors that significantly affected donor-related complication was size of the fascial defect, history of diabetes, muscle sparing type, and presence or absence of adjuvant chemotherapy. The risk cutoff value for fascial defect was 37.5 cm2. High-risk group complication rates analyzed by statistical method were significant compared to the low-risk group (26% vs 1.7%). These results may help surgeons to achieve better surgical outcomes and reduce postoperative burden.

BACKGROUND: Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) ...

Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) and breast-conserving therapy (BCT). The objective of the current study was to identify potential risk factors for LR and LRR after NCT and BCT.Individual patient data sets from 9 studies were pooled. The outcomes of interest were the occurrence of LR and/or LRR. A 1-stage meta-analytic approach was used. Cox proportional hazards regression models were applied to identify factors that were predictive of LR and LRR, respectively.A total of 9 studies (4125 patients) provided their data sets. The 10-year LR rate was 6.5%, whereas the 10-year LRR rate was 10.3%. Four factors were found to be associated with a higher risk of LR: 1) estrogen receptor-negative disease; 2) cN + disease; 3) a lack of pathologic complete response in axilla (pN0); and 4) pN2 to pN3 disease. The predictive score for LR determined 3 risk groups: a low-risk, intermediate-risk, and high-risk group with 10-year LR rates of 4.0%, 7.9%, and 20.4%, respectively. Two additional factors were found to be associated with an increased risk of LRR: cT3 to cT4 disease and a lack of pathologic complete response in the breast. The predictive score for LRR determined 3 risk groups; a low-risk, intermediate-risk, and high-risk group with 10-year LRR rates of 3.2%, 10.1%, and 24.1%, respectively.BCT after NCT appears to be an oncologically safe procedure for a large percentage of patients with breast cancer. Two easy-to-use clinical scores were developed that can help clinicians to identify patients at higher risk of LR and LRR after NCT and BCT and individualize the postoperative treatment plan and follow-up. Cancer 2018;124:2923-30. © 2018 American Cancer Society.

High-dose chemotherapy and autologous stem cell transplantation with melphalan, etoposide and carboplatin for high-risk osteosarcoma

Background In this study, we aimed to develop an objective staging system to determine the degree of nodal metastasis in breast cancer patients undergoing neoadjuvant systemic treatment (NST). Methods We reviewed the pretreatment computed tomography (CT) images of 392 breast cancer patients who received NST. The association between the patterns of the enlarged regional lymph nodes and treatment outcome was analyzed. Results In the development cohort of 260 patients, 88 (33.8%) patients experienced tumor recurrence and had a significantly higher number of enlarged lymph nodes on the pretreatment CT compared to patients with no recurrence. When patients were classified according to the numbers and locations of enlarged lymph nodes on pretreatment CT, the number of lymph nodes larger than 1 cm was most significantly associated with tumor recurrence. The accuracy of the CT-based nodal staging system was validated in an independent cohort of 132 patients. The presence of the enlarged supraclavicular nodes was associated with worse outcome, but the effect seemed to originate from the accompanied extensive axillary nodal burden. The prognostic effect of the objectively measured axillary nodal metastasis was more pronounced in hormone receptor-negative tumors. Conclusions We have developed and validated an objective method of nodal staging in breast cancer patients who undergo NST based on the number of enlarged axillary lymph nodes. Our system can improve the current subjective approach, which uses physical examination alone. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3380-8) contains supplementary material, which is available to authorized users.

Purpose Studies have suggested a potential role of patient’s co-morbidity in determining the survival outcomes of breast cancer. In this study, we examined the long-term oncologic outcomes in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions and analyzed the association between the co-morbidity and the use of adjuvant therapies. Methods The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. Results There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA I, II, and III, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of deaths (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA I, II and III group, respectively, p

The survival outcome according to conventional clinical N stage in the development cohort. Table S1. The incidence of axillary node involvement in patients with no suspicious nodes on CT (supplementary cohort A). Table S2. Clinicopathologic characteristics of patients who underwent primary surgery between July 2005 and June 2008 (supplementary cohort B). Table S3. Comparison of the CT-based nodal staging system and conventional clinical N staging (development cohort). (DOCX 83 kb)

Purpose We evaluated the risk of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) and investigated the predictive factors for CBC and IBTR in breast cancer patients with BRCA mutations and non-carriers at high-risk of hereditary breast and ovarian cancer (HBOC). Methods We analyzed prospectively collected clinical data of patients with unilateral breast cancer who were at high-risk for HBOC and were tested for the BRCA mutation between 2003 and 2013. Results The cohort comprised 540 patients with 45 BRCA1 carriers, 50 BRCA2 carriers, and 445 non-carriers. The median follow-up was 84.5 months. Overall, 61 patients (11.3%) developed CBC (24.4% for BRCA1 carriers, 20% for BRCA2 carriers, and 9% for non-carriers). The 10-year cumulative risk for CBC was 23.8% for BRCA1 carriers, 19.1% for BRCA2 carriers, and 9.8% for non-carriers (p = 0.174). Among the 277 patients who underwent breast-conserving surgery, 29 (10.5%) developed IBTR (9.1% for BRCA1 carriers, 16.7% for BRCA2 carriers, and 10.2% for non-carriers). The 10-year cumulative risk for IBTR for BRCA1 carriers, BRCA2 carriers, and non-carriers was 8.7%, 14.1%, and 20%, respectively (p = 0.577). BRCA1 (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.20-7.20; p = 0.019) and BRCA2 (HR, 2.88; 95% CI, 1.13-7.35; p = 0.027) mutations and negative estrogen receptor status (HR, 4.02; 95% CI, 1.60-10.08; p = 0.003) were the significant predictive factors for CBC, while tumor size ≥ 2 cm was predictive of IBTR (HR, 6.11; 95% CI, 2.03-18.33; p = 0.001). Conclusion While BRCA1/2 mutation carriers had a higher risk of developing CBC compared to non-carriers at high-risk of HBOC, the risk of IBTR was similarly high across breast cancer patients irrespective of the BRCA mutation. Further preventive strategies to reduce CBC and IBTR for all patients at high-risk of HBOC should be investigated.

Objective: Fine needle aspiration cytology (FNAC) is recommended by the World Health Organization as a diagnostic method for breast lesions. The morphological interpretation of liquid-based preparations (LBPs) remains a diagnostic challenge due to considerably altered cytomorphology. The aim of the current study was to compare cytomorphological characteristics of SurePath® (SP)-based LBP and conventional smear (CS) in breast FNACs. Study Design: The study included 77 benign and 60 malignant breast FNACs obtained by both SP and CS, all with tissue confirmation. Cases analyzed with both preparations were reviewed and compared, focusing on 10 cytomorphological features. Results: SP aspirates demonstrated notable cytomorphological alterations. Among them, a prominent three-dimensional configuration of cell clusters and frequent and conspicuous nucleoli were the most prominent characteristics of SP compared with CS. Overall diagnostic performances were comparable but were slightly lower for SP than CS (diagnostic accuracy of two reviewers; 87.6 and 90.5% for SP vs. 91.2 and 92.7% for CS, respectively). Conclusion: Although the reviewer should be aware of distinctive cytomorphological alterations, the SP technique is reliable for the evaluation of breast lesions with the advantage of easy interpretation and a diagnostic accuracy equivalent to CS.

Purpose: We investigated the prognostic impact of discordance between the receptor status of primary breast cancers and corresponding metastases. Methods: A total 144 patients with breast cancer and distant metastasis were investigated. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status of primary tumor and corresponding metastases were assessed. Tumor phenotype according to receptor status was classified as triplenegative phenotype (TNP) or non-TNP. Concordance and discordance was determined by whether there was a change in receptor status or phenotype between primary and metastatic lesions. Results: The rates of discordance between primary breast cancer and metastatic lesions were 18.1%, 25.0%, and 10.3% for ER, PR, and HER2, respectively. The rates of concordant non-TNP, concordant TNP and discordant TNP were 65.9%, 20.9%, and 13.2%, respectively. Patients with concordant ER/PR-negative status had worse postrecurrence survival (PRS) than patients with concordant ER/PR-positive and discordant ER/PR status (p= 0.001 and p= 0.021, respectively). Patients who converted from HER2-positive to negative after distant metastasis had worst PRS (p= 0.040). Multivariate analysis showed that concordant TNP was statistically significant factor for worse PRS (p< 0.001). Conclusion: Discordance in receptor status and tumor phenotype between primary breast cancer and corresponding metastatic lesions was observed. Patients with concordant TNP had worse long-term outcomes than patients with concordant non-TNP and discordant TNP between primary and metastatic breast cancer. Identifying the receptor status of metastatic lesions may lead to improvements in patient management and survival.

This paper suggests a two-phase look-ahead Banker’s algorithm for efficient operation of capacitated automated production systems. The algorithm improves the ability of detecting safe states of the previous one by considering the possibility of processing each job to completion at once as well as partial movement between jobs. The improved performance of the proposed algorithm is testified by performing numerical experiment in terms of (i) detection rate of safe states and (ii) system throughput and verified by using paired t-test. Key words : Capacitated Automated Production System, Banker’s Algorithm, Safe State, Detection Rate, Throughput요 약본 논문에서는 유한 용량 자동생산 시스템의 효율적인 운용을 위하여 기존에 제안된 은행가 (BA) 알고리즘의 단점을 개선시킨 2단계 Look-ahead 은행가 알고리즘을 제안하였다 . 제안된 알고리즘은 각 job 단위 별 전체 남은 공정의 처리 가능성뿐만 아니라 job들 간의 부분적인 이동 가능성을 동시에 고려하여 시스템 내부에 존재하는 job들의 완성 가능성을 결정함으로서 기존 알고리즘의 안전 상태 식별 능력을 향상시켰다 . 수치 실험을 통해 제안된 알고리즘의 향상된 성능을 (i) 안전 상태 탐색율과 (ii) 시스템 Throughput 을 기준으로 확인하였으며, paired t-test를 통해 검증하였다 .주요어 : 유한용량 자동생산 시스템, 은행가 알고리즘, 안전 상태, 탐색율, Throughput

목적 : 본 연구는 침생검을 통해 진단 받은 경화성 선증에 대해 추가적인 수술 없이 경과 관찰했을 때의 잠재적 안정성을 알아보고자 하였다. 방법 : 1996년 1월부터 2010년 5월까지 침생검을 통해 경화성 선증으로 진단된 143명의 환자의 145개 병변을 대상으로 (core-needle biopsies 118례, vacuum-assisted biopsies 27례) 의무기록 검토를 토대로 한 후향적 고찰이다. 결과 : 환자들의 BI-RADS(The American College of Radiology Breast Imaging Reporting and Data System) 분류는 다음과 같다: C3(n=8), C4a(n=123), C4b(n=11), C4c(n=e), C5(n=1). 그 중 14명은 조직검사를 재시행하였고 BI-RADS 분류 C5이면서 영상의학적 소견과 병리학적 소견의 불일치를 보인 1명의 환자가 침윤성 유방암으로 진단되어 수술을 시행하였다. 나머지 환자들은 정기적인 초음파 검사 및 유방촬영술을 통해 경과 관찰하였고, 평균 추적관찰 기간 40개월 동안 144개의 병변의 최종 BI-RADS 분류는 다음과 같다: C1(n=5), C2(n=107), C3(n=32), 경과 관찰기간 동안 142명의 환자에서 악성 유방질환이 발견된 환자는 없었다. 결론 : 침생검을 통해 경화성 선증으로 진단된 환자에 있어서 추가적인 수술 없이 정기적인 검진을 통하여 경과 관찰하는 것은 잠재적 안전성을 가지고 있다. 하지만 조직검사와 영상검사 결과의 불일치 소견을 보이는 경우 수술적 생검을 통한 최종 진단이 필요하다.

Engraftment syndrome (ES) and pre-engraftment syndrome (pre-ES) are both inflammatory conditions that occur after hematopoietic SCT (HSCT) and are characterized by non-infectious fever and skin rash. Although the pathogenesis is not fully understood, both syndromes are similar, and could be defined as a new clinical syndrome, named as peri-engraftment syndrome (peri-ES). We retrospectively analyzed the clinical records in 176 pediatric patients, following allogeneic HSCT. We utilized the definition of ES by Spitzer as the diagnostic criteria, excluding 'within 96 h of engraftment' criteria. Thirty cases developed peri-ES with a cumulative incidence of 17.0%. High cumulative incidence (50%) was seen in patients who underwent a double-unit cord blood transplantation (DUCBT; P0.01). Clinical findings of peri-ES are similar, regardless of the onset day, and encephalopathy was the most severe complication. In the DUCBT cohort, the use of TBI and early complete chimerism (≤ day 21) were identified as risk factors that predispose the development of peri-ES. We determined that both, ES and pre-ES, might have similar causes, which could be included in peri-ES. Particularly, it occurred more in DUCBT patients, which means that not only neutrophil engraftment but also immune reactions within the two units might contribute to peri-ES.

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

A positive resection margin after breast-conserving surgery (BCS) is the most important risk factor for tumor recurrence. Re-excision after BCS often results in unnecessary wider excisions, or even mastectomies and poor cosmetic results, as well as increased medical costs and patients’ anxiety. A nomogram for predicting positive resection margins may allow the surgeon to develop an individualized surgical plan. Data from 1,034 consecutive breast cancer patients with invasive or in situ breast cancer who initially underwent BCS between January 2008 and December 2009 were used to develop a nomogram for predicting positive resection margins. The nomogram was then validated independently using a cohort of 563 patients who underwent breast surgery in 2010. Multivariate logistic regression analysis showed that microcalcifications (OR 1.574, P = 0.034), grade 4 mammographic density (OR 4.515, P = 0.005), >0.5 cm difference in tumor size between magnetic resonance imaging and ultrasonography (OR 10.001, P < 0.0001), ductal carcinoma in situ (DCIS) on needle biopsy (OR 1.575, P = 0.044), and lobular component on needle biopsy (OR 3.985, P = 0.015) were independent predictors of positive resection margins. These significant variables were used to develop a nomogram for predicting positive resection margins after BCS; the AUCs of the study and the validation cohorts were 0.823 [95 % confidence interval (CI), 0.785–0.862] and 0.846 (95 % CI, 0.800–0.892), respectively. Our new nomogram using 5 variables that were determined before surgery to predict positive resection margins should aid the surgeon in developing individualized surgical plans for breast cancer patients who are scheduled for BCS.

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

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

Background: Improved understanding of factors affecting the accuracy of breast magnetic resonance imaging (MRI) after neoadjuvant systemic therapy (NST) can lead to more tailored use of MRI in deciding surgical extent after NST. Materials and Methods: We analyzed the imaging and clinicopathologic data of 463 patients who underwent NST. We aimed to investigate whether the molecular subtypes, as well as the use of targeted therapies, were associated with changes in the accuracy of MRI predicting residual tumor extent. Results: The accuracy of MRI predicting the residual tumor extent was most accurate in triple negative breast cancer and was least accurate in Luminal A subtype (Pearson's correlation coefficient of 0.754 and 0.531, respectively). Multivariate analysis suggested estrogen receptor status as an independent factor influencing the MRI accuracy. In HER2−amplified tumors, the use of HER2−targeted agents was associated with less accurate MRI prediction. Dual HER2−blockade by using trastuzumab and pertuzumab resulted in lowest MRI accuracy among the patients treated with HER2−targeted agents. Conclusion: The accuracy of MRI in predicting residual tumor extent was lowest in ER positive tumors treated with NST. In HER2 positive tumors, the use of HER2−targeted agents resulted in less accurate MRI after NST. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-16.

Purpose: The expression of Annexin A1 (ANXA1) is known to be reduced in human breast cancer; however, the role of ANXA1 expression in the development of breast cancer remains unclear. In this study, we determined the relationship between the expression features of ANXA1 and the prognostic factors of breast cancer. Methods: Human breast tissues were obtained from patients specimens who had undergone breast surgery or core needle biopsies. The patterns of ANXA1 expression were analyzed by immunohistochemical staining in relation to histopathological diagnosis, clinical characteristics and outcomes. Results: One hundred eighty-two cases were included and the mean age of the patients was 46.34 ± 11.5 years. A significant loss of ANXA1 expression was noted in both ductal carcinoma in situ (DCIS) and invasive carcinomas compared to normal breast tissues (p

Background: Recently indentified genetic variants from genome-wide association studies of breast cancer have not been validated in Asian population except for Chinese. We sought to confirm the association in ethnically distinct Korean women and to make genetic risk assessment model using multi-gene markers Materials and Methods: 3321 invasive breast cancer patients operated in Seoul National University Hospital and 3500 healthy control women from a population based cohort were genotyped for 5 single nucleotide polymorphisms (SNPs) using Taqman assay. The SNPs genotyped were rs2046210 (6q25.1), rs4973768 (3p), rs2981582 (FGFR2), rs3803662 (TNRC9), and rs889312 (MAP3K1). Results: The five SNPs were significantly associated with the risk of breast cancer in dominant, recessive, and co-dominant model (p-values from 0.012 to 3.41E-08). Minor allele frequencies were between 0.2 and 0.5. Odds ratios were between 1.14 and 1.51. Multi-gene logistic regression risk model was made with this 5 SNPs. Women who have all protective variants showed odds ratio of 0.43, while women who are homozygous for risk variants in all 5 SNPs showed odds ratio of 2.36 compared with women with the most common genotype. Conclusion: We found that 5 SNPs from GWAS in mostly women of European ancestry were also significantly associated with breast cancer risk in Korean women. The multi-gene risk assessment model might be useful to classify women into relevant risk groups. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-19.