Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006) / 한국유방암학회지

Purpose@#In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. @*Methods@#In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. @*Results@#Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. @*Conclusion@#Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006) / 한국유방암학회지

Purpose@#In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. @*Methods@#In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. @*Results@#Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. @*Conclusion@#Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Urinary Iodine Concentration and Thyroid Peroxidase Antibodies in the Korean Population Using Korea National Health and Nutrition Examination Survey VI

Background and Objectives@#This study was planned to investigate the relationship between iodine intake and thyroid peroxidase antibody in Korean population. @*Materials and Methods@#We used the data of the 6th Korea National Health and Nutrition Examination Survey from 2013 to 2015. A total of 6564 subjects who had the data of thyroid function test were included. We analyzed urinary iodine concentration and thyroid peroxidase antibody using the complex sample method. Univariate and multivariate analysis were performed according to clinical factors and thyroid function tests. @*Results@#In the multivariate analysis, the thyroid peroxidase antibody positivity was not related to urinary iodine concentration in the total group (p=0.102), male group (p=0.245) and female group (p=0.098). The urinary iodine concentration was associated with thyroid stimulating hormone (TSH) (p=0.001) and free T4 (p=0.001) but not associated with thyroid peroxidase antibody (p=0.218). When high TSH group was divided into the positive and negative thyroid peroxidase antibody, high TSH group with negative thyroid peroxidase antibody increased according to increasing urinary iodine concentration (p＜0.001).But there was no difference in the high TSH group with positive thyroid peroxidase antibody (p=0.826). @*Conclusion@#This study did not show a statistically significant relationship between urinary iodine concentration and thyroid peroxidase antibody. As urinary iodine concentration increased, thyroid function was decreased only in the negative thyroid peroxidase antibody group. This confirmed that the increased urinary iodine concentration caused hypothyroidism which was not associated with thyroid peroxidase antibody.

Development of an Excel Program for the Updated Eighth American Joint Committee on Cancer Breast Cancer Staging System

PURPOSE: The eighth American Joint Committee on Cancer staging system for breast cancer was recently published to more accurately predict the prognosis by adding biomarkers such as estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. However, this system is very complicated and difficult to use by clinicians. The authors developed a program to aid in setting up the staging system and confirmed its usefulness by applying it to theoretical combinations and actual clinical data. METHODS: The program was developed using the Microsoft Excel Macro. It was used for the anatomic, clinical and pathological prognostic staging of 588 theoretical combinations. The stages were also calculated the stages using 840 patients with breast cancer without carcinoma in situ or distant metastasis who did not undergo preoperative chemotherapy. RESULTS: The anatomic, clinical and pathological prognostic stages were identical in 240 out of 588 theoretical combinations. In the actual patients' data, stages IB and IIIB were more frequent in clinical and pathological prognostic stages than in the anatomic stage. The anatomic stage was similar to the clinical prognostic stage in 58.2% and to the pathological prognostic stage in 61.9% of patients. Oncotype DX changed the pathological prognostic stage in 2.1% of patients. CONCLUSION: We developed a program for the new American Joint Committee on Cancer staging system that will be useful for clinical prognostic prediction and large survival data analysis.

The Practice Patterns and Perceptions of Korean Surgeons Regarding Margin Status after Breast-Conserving Surgery / 한국유방암학회지

Two consecutive surveys for breast surgeons in Korea were conducted to comprehend the practice patterns and perceptions on margin status after breast-conserving surgery. The surveys were conducted online in 2014 (initial) and 2016 (follow-up). A total of 126 and 88 responses were obtained in the initial and follow-up survey, respectively. More than 80% of the respondents replied to routinely apply frozen section biopsy for intraoperative margin assessment in both surveys. Re-excision recommendations of the margin for invasive cancer significantly changed from a close margin to a positive margin over time (p=0.033). Most of the respondents (73.8%) defined a negative margin as “no ink on tumor” in invasive cancer, whereas more diverse responses were observed in ductal carcinoma in situ cases. The influence of guideline establishment for negative margins has been identified. A high uptake rate of intraoperative frozen section biopsy was noted and routine use needs reconsideration.

Development of Individual Survival Estimating Program for Cancer Patients' Management / 대한의료정보학회지

OBJECTIVES: The goal of this report is to present an individual patient's survival estimation curve using the each institution's survival data after Cox proportional hazard analysis. METHODS: The program was developed in three parts: input of basic data from Cox proportional hazard analysis, input of individual patient's covariates, and presentation of individual patient's survival curve. In the first part, the average survival rates with each survival time were entered as the means of covariates using the results of Cox proportional hazard analysis. In the second part, the individual patient's values of each covariate were entered for the calculation of survival estimation. In the third part, the survival curve was displayed according to the input data. RESULTS: The data of 2,652 breast cancer patients were analyzed. Cox regression analysis was conducted using the covariates of age, tumor size, N stage, and M stage. The individual patient's survival curve was presented using the basic data and covariate factors. In the breast cancer patients, the program presented survival curves according to each patient's age, tumor size, N stage, and M stage. The data of 251 thyroid cancer patients were analyzed by a similar method. CONCLUSIONS: We developed a program to present individual survival curves of cancer patients. This program will be useful for clinicians to assist their decision-making and discussion with patients.

Validation of Risk Assessment Models for Predicting the Incidence of Breast Cancer in Korean Women / 한국유방암학회지

PURPOSE: The Gail model is one of the most widely used tools to assess the risk of breast cancer. However, it is known to overestimate breast cancer risk for Asian women. Here, we validate the Gail model and the Korean model using Korean data, and subsequently update and revalidate the Korean model using recent data. METHODS: We validated the modified Gail model (model 2), Asian American Gail model, and a previous Korean model using screening patient data collected between January 1999 and July 2004. The occurrence of breast cancer was confirmed by matching the resident registration number with data from the Korean Breast Cancer Registration Program. The expected-to-observed (E/O) ratio was used to validate the reliability of the program, and receiver operating characteristics curve analysis was used to evaluate the program's discriminatory power. There has been a rapid increase in the incidence of breast cancer in Korea, and we updated and revalidated the Korean model using incidence and mortality rate data from recent years. RESULTS: Among 40,229 patients who were included in the validation, 161 patients were confirmed to have developed breast cancer within 5 years of screening. The E/O ratios and 95% confidence intervals (CI) were 2.46 (2.10-2.87) for the modified Gail model and 1.29 (1.11-1.51) for the Asian American Gail model. The E/O ratio and 95% CI for the Korean model was 0.50 (0.43-0.59). For the updated Korean model, the E/O ratio and 95% CI were 0.85 (0.73-1.00). In the discriminatory power, the area under curve and 95% CI of the modified Gail model, Asian American Gail model, Korean model and updated Korean model were 0.547 (0.500-0.594), 0.543 (0.495-0.590), 0.509 (0.463-0.556), and 0.558 (0.511-0.605), respectively. CONCLUSION: The updated Korean model shows a better performance than the other three models. It is hoped that this study can provide the basis for a clinical risk assessment program and a future prospective study of breast cancer prevention.

Development and Validation of Web-Based Nomograms to Predict Postoperative Invasive Component in Ductal Carcinoma in Situ at Needle Breast Biopsy / 대한의료정보학회지

OBJECTIVES: Although sonography-guided core needle biopsy is a highly targeted method, there is a possibility of an invasive component after surgical excision of ductal carcinoma in situ (DCIS) of the breast. This study was performed to develop and validate nomograms to predict the postoperative invasive component in DCIS at core needle biopsy. METHODS: Two nomograms were developed using the data of previous meta-analysis and multivariate analysis. Nomograms were validated externally using the data of the authors' affiliation. The accuracy was validated by the expected-to-observed ratio and the Hosmer-Lemeshow goodness-of-fit test. Discrimination was validated by the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis. RESULTS: The nomogram using the meta-analysis study data was developed at http://dcis-m.surgery.kr.pe/, and the nomogram using the multivariate analysis study data was developed at http://dcis-k.surgery.kr.pe/. The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram using multivariate analysis data (p = 0.131) was better calibrated than that using meta-analysis data (p < 0.001). ROC curve analysis showed statistically significant power of discrimination in both nomograms (AUC = 0.776, 0.751). CONCLUSIONS: Both nomograms showed statistically significant discriminatory power, but the nomogram using the data of multivariate analysis was simpler and more reliable. These would be useful for the prediction of invasive cancer and the need for sentinel node biopsy in DCIS at core needle biopsy.

Characteristics of the Germline MEN1 Mutations in Korea: A Literature Review / 대한내분비외과학회지

PURPOSE: Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant disease caused by the MEN1 germline mutation. We reviewed previous reports in order to summarize the characteristics of germline MEN1 mutation in Korea. METHODS: We retrieved the relevant literature regarding MEN1 germline mutation in Korea using the Pubmed (http://www.pubmed.org/) and Koreamed (http://www.koreamed.org/) databases from 2000 to 2012. We evaluated the pedigree of the patients in order to exclude the same, repeated families. We collected all data on the types of mutations and clinical characteristics. RESULTS: There were nine studies with 12 cases of MEN1 mutations in Korea. Two cases were sporadic MEN-1. C.196_200dupAGCCC was reported in three families. There were six cases of frameshift mutation, three cases of missense mutation, two cases of nonsense mutation, and one case of splice site mutation. Five mutations were novel mutations not previously reported. CONCLUSION: We summarized the characteristics of germline MEN1 mutations in Korea. Genetic testing of MEN1 is rare in Korea; however, it will be useful in preclinical diagnosis and genetic counseling.

Bromocriptine-Treated Giant Lactating Adenoma: A Case Report with Imaging Findings

Lactating adenoma is a benign breast disease that occurs during pregnancy or lactational periods. Here we report on a case of rapidly enlarging lactating adenoma in a 28-year-old postpartum woman, which was mistaken for a malignant breast tumor. Treatment with bromocriptine resulted in a rapid reduction of the mass, suggesting that bromocriptine could be used for shrinking lactating adenoma and to facilitate surgical removal. We describe its imaging findings, including ultrasonographic findings with correlative histologic features, confirmed by surgical excision.

Oncologic manifestations of neurofibromatosis type 1 in Korea / 대한외과학회지

PURPOSE: The aim of this study was to investigate the incidence and spectrum of malignant tumors in Korean neurofibromatosis type 1 (NF1) patients. METHODS: We retrospectively reviewed 125 patients who were diagnosed with NF1 at a single institution from 1995 to 2010. The incidence, location, histologic type, and radiologic findings of malignant tumors as well as development of multiple primary tumors were analyzed. RESULTS: Eighteen malignant tumors occurred in 16 patients (12.8%) among 125 Korean NF1 patients; 9 carcinomas, 8 sarcomas and 1 central nervous system (CNS) tumor. Five tumors were of nervous system origin and 13 were non-nervous system tumors. The locations of the tumors were as follow: 1 CNS, 2 lung, 3 breast, 3 stomach, 3 small bowel, 1 colon, 1 liver, 1 uterus, 1 neck, and 2 in extremities. Three malignant peripheral nerve sheath tumors (MPNSTs) occurred at the neck and extremity, and one in the liver. All three gastrointestinal stromal tumors (GISTs) had multiple tumors in the jejunum, and one MPNST and one pheochromocytoma were accompanied in two GISTs. Multiple primary tumors, benign or malignant were reported in 4 patients (25.0%), synchronously or metachronously. CONCLUSION: Korean NF1 patients had a high risk of developing malignant tumors. The common malignant tumors in Koreans such as breast, lung and stomach cancers developed frequently in addition to the NF1-related tumors such as MPNST or GIST.

Bilateral adrenal pheochromocytoma with a germline L790F mutation in the RET oncogene / 대한외과학회지

About ten percent of pheochromocytomas are associated with familial syndrome. Hereditary pheochromocytoma has characteristics of early onset, multifocality and bilaterality. We experienced a case of 44-year-old man with bilateral pheochromocytoma without evidence of medullary thyroid cancer. Genetic test detected a L790F germline mutation of RET oncogene. The author found a necessity for genetic tests in cases of young-age, bilateral pheochromocytoma.

Estimating the Risks and Benefits of Tamoxifen for Prophylactic Breast Cancer Chemoprevention in Korea / 한국유방암학회지

PURPOSE: According to the National Surgical Adjuvant Breast and Bowel Project P1 (NSABP-P1) study, tamoxifen can prevent 49% of invasive breast cancers in patients who have a 5-year risk of 1.67% or more. Because tamoxifen is associated with both adverse effects (endometrial cancer, stroke, pulmonary embolism) and protective effect (fracture prevention), it is necessary to weigh the risks and benefits of using tamoxifen for prevention in Korean women. This study weighed those risks and benefits. METHODS: Data were reviewed on the incidences of breast cancer, hip fracture, endometrial cancer and stroke in the absence of tamoxifen treatment in Korean women. We also reviewed NSABP-P1 data on the effects of tamoxifen on these outcomes. A risk-benefit index was calculated according to age and specific risk of breast cancer. Sensitivity analyses were performed with assumptions regarding the effects of tamoxifen. RESULTS: Compared to U.S. women, the numbers of hip fractures and endometrial cancers were lower, but the number of strokes was much higher. The net benefit of tamoxifen was reduced with increasing age because of a high risk of stroke in older women. Older Korean women had more risk than benefit from tamoxifen chemoprevention. Only women younger than age 40 had a positive risk-benefit index with an average 5-year risk of breast cancer in Korea. Sensitivity analysis showed that this result was robust. CONCLUSION: Women under the age 40 had more benefit than risk from tamoxifen chemoprevention. Tamoxifen chemoprevention should be limited to Korean women younger than age 40.

Estimating the Risks and Benefits of Tamoxifen for Prophylactic Breast Cancer Chemoprevention in Korea / 한국유방암학회지

PURPOSE: According to the National Surgical Adjuvant Breast and Bowel Project P1 (NSABP-P1) study, tamoxifen can prevent 49% of invasive breast cancers in patients who have a 5-year risk of 1.67% or more. Because tamoxifen is associated with both adverse effects (endometrial cancer, stroke, pulmonary embolism) and protective effect (fracture prevention), it is necessary to weigh the risks and benefits of using tamoxifen for prevention in Korean women. This study weighed those risks and benefits. METHODS: Data were reviewed on the incidences of breast cancer, hip fracture, endometrial cancer and stroke in the absence of tamoxifen treatment in Korean women. We also reviewed NSABP-P1 data on the effects of tamoxifen on these outcomes. A risk-benefit index was calculated according to age and specific risk of breast cancer. Sensitivity analyses were performed with assumptions regarding the effects of tamoxifen. RESULTS: Compared to U.S. women, the numbers of hip fractures and endometrial cancers were lower, but the number of strokes was much higher. The net benefit of tamoxifen was reduced with increasing age because of a high risk of stroke in older women. Older Korean women had more risk than benefit from tamoxifen chemoprevention. Only women younger than age 40 had a positive risk-benefit index with an average 5-year risk of breast cancer in Korea. Sensitivity analysis showed that this result was robust. CONCLUSION: Women under the age 40 had more benefit than risk from tamoxifen chemoprevention. Tamoxifen chemoprevention should be limited to Korean women younger than age 40.

The Prevalence of Ovarian Cancer in Korean Women at High-Risk for Hereditary Breast-Ovarian Cancer / 한국유방암학회지

PURPOSE: Few studies have reported ovarian cancer risks in Korean patients with the BRCA1/2 mutation. We investigated the prevalence of ovarian cancer in Korean women at high risk for hereditary breast-ovarian cancer (HBOC) syndrome and reviewed the clinicopathological factors of ovarian cancer. METHODS: Female subjects who were enrolled in the Korean Hereditary Breast Cancer study were included. The questionnaire included a personal and family history of cancer. The BRCA1/2 mutation and CA-125 level were tested at the time of enrollment. A transvaginal ultrasonogram (TVUS) was recommended for subjects with an elevated CA-125 level. RESULTS: A total of 1,689 patients were included. No ovarian cancer was newly diagnosed by CA-125 level or TVUS during the enrollment. The prevalence of ovarian cancer was 1.71% in BRCA1/2 mutation carriers and 0.39% in non-carriers. Among 11 patients with ovarian cancer, five had the BRCA1 mutation and one had the BRCA2 mutation. The most common histopathological type was serous cystadenocarcinoma. No difference in clinicopathological findings between BRCA1/2 mutation carriers and non-carriers was observed. CONCLUSION: The prevalence of ovarian cancer was 58-fold elevated in women at high-risk for HBOC syndrome and 146-fold elevated in the BRCA1 subgroup, compared with the Korean general population. Further investigation with a long-term follow-up is required to evaluate BRCA1/2 gene penetrance.

Epidermoid Cyst of the Spleen Presenting as Acute Abdominal Pain

Splenic epidermoid cyst is a rare disease affecting the spleen. We report a 24-year-old male who presented with acute abdominal pain. Computed tomography scan of the abdomen revealed a huge cystic lesion of the spleen. At laparotomy, a huge cyst was found arising from the low pole of the spleen. It was removed by splenectomy. Histopathological findings were consistent with splenic epidermoid cyst.

Epidermoid Cyst of the Spleen Presenting as Acute Abdominal Pain

Splenic epidermoid cyst is a rare disease affecting the spleen. We report a 24-year-old male who presented with acute abdominal pain. Computed tomography scan of the abdomen revealed a huge cystic lesion of the spleen. At laparotomy, a huge cyst was found arising from the low pole of the spleen. It was removed by splenectomy. Histopathological findings were consistent with splenic epidermoid cyst.

Spontaneous Retroperitoneal Hemorrhage from Ruptured Suprarenal Artery Aneurysm

Retroperitoneal hemorrhage from a ruptured suprarenal artery aneurysm is very rare. We report on a 34-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage for suprarenal artery aneurysm. The patient made a full recovery with no evidence of further hemorrhage.

Characteristics of the RET Oncogene Germline Mutations in Korean Medullary Thyroid Carcinoma: A Literature Review / 대한내분비외과학회지

PURPOSE: Germline mutation of the RET oncogene results in multiple endocrine neoplasia (MEN) types 2A and 2B and familial medullary thyroid cancer (FMTC). We reviewed the literature to determine the mutation patterns of the RET oncogene in Koreans with MEN-2A, 2B and FMTC. METHODS: We retrieved the relevant literature using the PubMed (http://www.pubmed.org/) and KoreaMed (http://www.koreamed.org/) databases concerning the RET germline mutations in Korea from 1998 to 2010. We evaluated the pedigree of the patients to exclude the same, repeated families. We collected all the data on the types of mutations and the clinical syndromes. RESULTS: There were 21 studies with a total of 25 families. In the patients with MEN-2A and FMTC, there were 14 mutations (56%) in codon 634, 6 mutations (24%) in codon 618, 2 mutations (8%) in codon 631 and one mutation (4%) in codon 768. In the patients with MEN-2B, there were 2 mutations (8%) in codon 918. D631Y is an extremely rare mutation, but two families with such a mutation existed in Korea. The frequency of codon 634 mutations in the patients with MEN-2A was relatively lower than that of the previously reports from western countries and the frequency of codon 618 mutations was relatively higher than that in the western countries. CONCLUSION: This study shows there are hot spots and genotype- phenotype correlations for the RET oncogene mutations in Koreans.

Somatic Mutational Analysis of MEN1 and Phenotypic Correlation in Sporadic Parathyroid Tumors

PURPOSE: MEN1 gene mutation causes multiple endocrine neoplasia type 1. It also suggests that somatic MEN1 gene mutation plays a role in sporadic endocrine tumor. In this study, we examined whether somatic mutations of MEN1 gene are responsible for sporadic parathyroid tumors and correlate with clinical manifestations of parathyroid tumors. METHODS: Somatic mutation of MEN1 gene in the formalin-fixed, paraffin-embedded parathyroid tumor tissue from 8 adenomas, 2 carcinomas and 1 hyperplasia were analyzed by direct sequencing. Clinicopathological parameters were reviewed from medical records and compared with the mutational data. RESULTS: Eight of eleven (73%) sporadic parathyroid tumors had somatic MEN1 mutations of 14 different types. In the 14 types, 13 were a point mutation which is composed of 8 missense mutations, 2 nonsense mutations and 3 silent mutations. One of 14 types is a frameshift deletion of 27 base pairs in exon 2. Somatic mutation was frequent in the exon 2 and exon 10. Four types of polymorphism were found. There was no correlation between the presence of mutations and clinicopathological phenotype of parathyroid tumors. CONCLUSION: This result suggests that somatic mutation of MEN1 gene plays a definite role in sporadic parathyroid tumor formation.