Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia

Background/Aims@#Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database. @*Methods@#This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]). @*Results@#The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS. @*Conclusions@#Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.

Characteristics and survival of patients with atypical chronic myeloid leukemia

No abstract available.

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension

The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1–7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1–7)/Mas receptor and ACE2/Ang-(1–9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.

Diagnostic Accuracy of Hepatic Vein Arrival Time Performed with Contrast-Enhanced Ultrasonography for Cirrhosis: A Systematic Review and Meta-Analysis

BACKGROUND/AIMS: We identified reports in the literature regarding the diagnostic accuracy of hepatic vein arrival time (HVAT) measured by contrast-enhanced ultrasonography (CEUS) to assess hepatic fibrosis in cirrhosis. METHODS: The Ovid MEDLINE, Embase, and Cochrane databases were searched for all studies published up to 23 July 2015 that evaluated liver status using CEUS and liver biopsy (LB). The QUADAS-II (quality assessment of diagnostic accuracy studies-II) was applied to assess the internal validity of the diagnostic studies. Selected studies were subjected to a meta-analysis with MetaDisc 1.4 and RevMan 5.3. RESULTS: A total of 12 studies including 844 patients with chronic liver disease met our inclusion criteria. The overall summary sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the HVAT measured by CEUS for the detection of cirrhosis compared to LB were 0.83 (95% confidence interval [CI], 0.77 to 0.89), 0.75 (95% CI, 0.69 to 0.79), 3.45 (95% CI, 1.60 to 7.43), and 0.28 (95% CI, 0.10 to 0.74), respectively. The summary diagnostic odds ratio (random effects model) was 15.23 (95% CI, 3.07 to 75.47), the summary receiver operator characteristics area under the curve was 0.74 (standard error [SE]=0.14), and the index Q was 0.69 (SE=0.11). CONCLUSIONS: Based on a systematic review, the measurement of HVAT by CEUS exhibited an increased accuracy and correlation for the detection of cirrhosis.

Idiopathic Retroperitoneal Fibrosis Associated with Rheumatoid Arthritis in a Patient with Concomitant Chronic B Viral Hepatitis

Retroperitoneal fibrosis (RPF) is a rare, progressive disease characterized by chronic non specific inflammation of the retroperitoneum. Although the pathogenesis of idiopathic retroperitoneal fibrosis (IRF) remains unclear, IRF has been reported in association with autoimmune disorders. However, few cases of IRF associated with rheumatoid arthritis (RA) have been reported. We experienced a rare case of IRF in a patient with RA and chronic B viral hepatitis. A 39-year-old Korean man with RA and hepatitis B was referred to our hospital due to left hydronephrosis. An abdominal computed tomography (CT) scan and magnetic resonance imaging (MRI) showed a diffuse infiltrating retroperitoneal mass around the abdominal aorta and left ureter. The patient underwent intraureteral stent insertion and was treated with corticosteroid. Three months later, the follow up abdominal CT showed that the retroperitoneal mass had decreased in size. Herein, we report the first case of coexistent IRF, RA, and chronic B viral hepatitis with a literature review.

Mesenchymal stem cell therapy for liver fibrosis

Currently, the most effective treatment for end-stage liver fibrosis is liver transplantation; however, transplantation is limited by a shortage of donor organs, surgical complications, immunological rejection, and high medical costs. Recently, mesenchymal stem cell (MSC) therapy has been suggested as an effective alternate approach for the treatment of hepatic diseases. MSCs have the potential to differentiate into hepatocytes, and therapeutic value exists in their immune-modulatory properties and secretion of trophic factors, such as growth factors and cytokines. In addition, MSCs can suppress inflammatory responses, reduce hepatocyte apoptosis, increase hepatocyte regeneration, regress liver fibrosis and enhance liver functionality. Despite these advantages, issues remain; MSCs also have fibrogenic potential and the capacity to promote tumor cell growth and oncogenicity. This paper summarizes the properties of MSCs for regenerative medicine and their therapeutic mechanisms and clinical application in the treatment of liver fibrosis. We also present several outstanding risks, including their fibrogenic potential and their capacity to promote pre-existing tumor cell growth and oncogenicity.

Relationship between Tetrahydrobiopterin and Portal Hypertension in Patients with Chronic Liver Disease

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.

Rapid Isolation of Adipose Tissue-Derived Stem Cells by the Storage of Lipoaspirates

PURPOSE: This study examined a rapid isolation method decreasing the time and cost of the clinical application of adipose tissue-derived stem cells (ASCs). MATERIALS AND METHODS: Aliquots (10 g) of the lipoaspirates were stored at 4degrees C without supplying oxygen or nutrients. At the indicated time points, the yield of mononuclear cells was evaluated and the stem cell population was counted by colony forming unit-fibroblast assays. Cell surface markers, stem cell-related transcription factors, and differentiation potentials of ASCs were analyzed. RESULTS: When the lipoaspirates were stored at 4degrees C, the total yield of mononuclear cells decreased, but the stem cell population was enriched. These ASCs expressed CD44, CD73, CD90, CD105, and HLA-ABC but not CD14, CD31, CD34, CD45, CD117, CD133, and HLA-DR. The number of ASCs increased 1x1014 fold for 120 days. ASCs differentiated into osteoblasts, adipocytes, muscle cells, or neuronal cells. CONCLUSION: ASCs isolated from lipoaspirates and stored for 24 hours at 4degrees C have similar properties to ASCs isolated from fresh lipoaspirates. Our results suggest that ASCs can be isolated with high frequency by optimal storage at 4degrees C for 24 hours, and those ASCs are highly proliferative and multipotent, similar to ASCs isolated from fresh lipoaspirates. These ASCs can be useful for clinical application because they are time- and cost-efficient, and these cells maintain their stemness for a long time, like ASCs isolated from fresh lipoaspirates.

Complete Endoscopic Resection of Very Early Stage Gastric Plasmacytoma

Gastric plasmacytomas are very rare, and most are not detected until the disease has progressed to an advanced stage. However, there have been recent reports of cases of early-stage gastric plasmacytoma, in which neoplastic cells are confined to the mucosa or submucosa. Here we report a case of a very early stage gastric plasmacytoma that was confined to the lamina propria of the gastric mucosa. The lesion was successfully and completely removed by endoscopic submucosal dissection, and the surveillance endoscopy showed no recurrence during the follow-up of 40 months. This report appears to be the first documented case of complete endoscopic removal of a primary gastric plasmacytoma.

Simultaneous Occurrence of Hodgkin's Disease and Multiple Myeloma / 대한혈액학회지

A 71-year-old man who had no prior history of chemotherapy or radiation therapy was diagnosed with nodular sclerosis Hodgkin's disease (HD) and IgA-kappa multiple myeloma (MM) simultaneously. The patient achieved a complete response of HD and a minor response of MM after 6 cycles of COPP/ABV chemotherapy. Thereafter, he had received oral mephalan and prednisolone without disease progression for 12 months. At 27-month follow-up, he succumbed to overwhelming pneumonia and septic shock with progressive disease of MM. We present this case as a first report of simultaneous occurrence of HD and MM in South Korea.

A Case of Acute Myelogenous Leukemia Presenting as Polyradiculomyelopathy and Peripheral Facial Paralysis

It is uncommon for acute myelogenous leukemia to present a symptom referrable to a tumor mass. A rare case of spinal epidural granulocytic sarcoma preceding the diagnosis of acute myelogenous leukemia is described. Also, reports of acute myelogenous leukemia associated with facial palsy have been extremely rare. We report a patient who had facial nerve paralysis and polyradiculomyelopathy due to granulocytic sarcoma as the presenting symptoms of acute myeloid leukemia.

A case of metastatic hepatocellular carcinoma to orbit with superior orbital fissure syndrome / 대한내과학회지

The superior orbital fissure syndrome is a rare condition characterized by opthalmoplegia, ptosis, and proptosis of the eye, fixation and dilation of the pupil, and anesthesia of the upper eyelid and forehead. Tumor metastasis to the orbit is uncommon and there were only 11 histologically proven cases of metastatic hepatocellular carcinoma to the orbit. There was only one case of metastatic hepatocellular carcinoma to the orbit with superior orbital fissure syndrome. The prognosis were poor for all reported cases, but palliative radiotherapy could be some help. We report a rare case of metastatic hepatocellular carcinoma to the orbit with superior orbital fissure syndrome.

A case of double primary cancer of hepatocellular carcinoma and mucoepidermoid carcinoma in the liver / 대한내과학회지

Mucoepidermoid carcinoma is a common malignant tumor of the salivary glands, but rare in other sites. Only 10 cases of mucoepidermoid carcinoma of liver have been reported, and there was 1 case of double primary cancer of hepatocellular carcinoma and mucoepidermoid carcinoma. The definite diagnosis and pathogenesis are still controversial. However, hepatocellular carcinoma is the second most common cancer in Korea. Its etiology is better known compared to mucoepidermoid carcinoma. We report a rare case of double primary cancer of mucoepidermoid carcinoma and hepatocellular carcinoma in liver.

The Efficacy and Safety of Docetaxel in Patients with Anthracychne pretreated Metastatic Breast Cancer: A Multicenter Phase II Study / 대한암학회지

PURPOSE: Tbis phase II study was performed to evaluate the efficacy and safety of docetaxel in patients with anthracycline-pretreated metastatic breast cancer (MBC). MATERIALS AND METHODS: From September 1996 to January 1998, 27 patients with metastatic breast cancer from 31 to 63 years of age with a performance status of 0 to 2 were registered in the phase II trial. All patients had metastatic breast cancer which had progressed or relapsed 2 during or after treatment with an anthracycline-based regimen. Docetaxel 75 mg/m2 was ad- ministered over 1 hour every 21 days until disease progression was documented or until toxic effects precluded further therapy. All patients received dexamethasone orally at the dose of 16 mg on days -1, 0, 1 of each cycle. RESULTS: Objective responses were seen in 9 of 25 assessable patients (two complete and seven partial responses), with an overall objective response rale of 36%. The median duration of response was 36 weeks (range 19.0~40.5). The median time to progression and survival duration were 17.5 and 69 weeks, respectively, for assessable patients. One hundred fifty cycles (median, five) of docetaxel were administered. Among 27 patients assessable for toxicity, the following side effects were reported: nadir neutropenia grade 3 (4 patients) and grade 4 (22 patients); grade 2 stomatitis (6 patients); grade 2 alopecia (5 patients); grade 2 to 3 neurosensory toxicity (4 patients); no hypersensitivity reaction; mild fluid retention (4 patients). CONCLUSION: Docetaxel is an active agent in patients with antracycline-pretreated metastatic breast cancer. Docetaxel was associated with severe but reversible neutropenia. Dexamethasone prevented hypersensitivity reactions and appeared to ameliorate fluid retention.

Efficacy of Chronic Oral Etoposide and Tamoxifen in the Far-Advanced Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: This study evaluated the use and efficacy of chronic oral etoposide plus tamoxifen as a palliative treatment in 30 patients with far-advanced HCC in whom surgical resection, percutaneous ethanol injection or transarterial chemoembolization(TACE) was not possible. METHODS: To be eligible for the study, patients had to have objectively measurable or evaluable tumors, adequate hematologic profiles and hepatorenal functions, had to be between 20 and 75 years of age, and had to have an ECOG performance status of less than or equal to 2. The treatment included etoposide, 50 mg/m2/day, taken orally for 21 days, and tamoxifen, 40 mg/day, taken orally for 21 days. Each cycle was repeated every 5 weeks. RESULTS: Two patients(7%) achieved a partial response(PR) and 16 patients(53%) achieved a stable disease(SD) with a median time-to-progression of 5 months(range: 2-24). Median of patients survival with the response of PR or SD and those patients with the response of progressive disease(PD) was 10 months and 7 months, respectively(p=0.0004). Of the 20 patients with initial elevated serum alpha-fetoprotein(> or =500 ng/ml), 9 patients(45%) experienced a significant(> or =50%) decrease in their values after chemotherapy and all 9 patients achieved objective tumor response of more than or equal to SD. Among the 30 patients in the study, 10 patients(33%) achieved performance status improvements of grade according to the ECOG criteria and 6 patients(20%) experienced improvements of subjective symptoms, such as abdominal pain, abdominal fullness and anorexia. CONCLUSION: Based on our results, the use of chronic oral etoposide plus tamoxifen as a palliative treatment for the far-advanced hepatocellular carcinoma are beneficial. A randomized two-arm study may be warranted to validate the results of this study.

Effect of 5 - FU plus leucovorin for adjuvant chemotherapy according to dose related factors in colon cancer / 대한내과학회지

BACKGROUND: In patients with stage C colon cancer, surgery followed by adjuvant chemotherapy with 5-fluorouracil (5-FU)/leucovorin (LV) is considered to be the standard treatment. However, the objects of adjuvant therapy and the duration of treatment are still matters of controversy. We investigated the effect of dose related factor(delivered total dose of 5-FU per body square meter, actual dose intensity and relative dose intensity) of the adjuvant 5-FU/leucovorin regimen on survival in coloncancer. METHODS: Of the colon cancer patients with Duke's B2 and C stage diseases treated with curative resection from December, 1990 to December, 1996, 139 patients treated with 5-FU/LV as an adjuvant chemotherapy were evaluated. The delivered total dose of 5-FU per body square meter, actual dose intensity and relative dose intensity were obtained. The patients were divided into two groups according to the median value of each factor and the survival rates were compared. RESULTS: The total dose of 5-FU administrated per body square meter had a significant effect on the 5-year disease free and overall survival in stage B2 and C colon cancer patients(B2; p=0.025, p=0.045, respectively, C; p=0.011, p=0.0002, respectively). But survival was not affected by the dose intensity. Multivariate analysis demonstrated that only the total dose of 5-FU administrated per body surface area affected the 5-year disease free and overall survival(p=0.0016, p=0.0007, respectively). CONCLUSION: It can be concluded that the total dose of 5-FU administered is more important than the DI in adjuvant chemotherapy of colon cancer and the total dose of 5-FU had a significant effect on the survival rate in colon cancer patients. To confirm the total dose effect of 5-FU on survival in this study, multi-institutional, prospective randomized studies should be carried out.

Efficacy of Gemcitabine Chemotherpy in Advanced Non-small cell Lung Cancer ( NSCLC ): A Phase 2 Study / 대한암학회지

PURPOSE: To evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite against advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Forty patients with unresectable stage IIIb to IV, pathologacally documented NSCLC were evaluated. Patients received gemcitabine 1000 mg/m, as a 30 to 60-min, intravenous infusion on days 1, 8 and 15, which was repeated every 28 days. Responses were assessed every two courses. Twenty-five to fifty percent dose reduction was permitted, ptovided that overall toxicity was severe according to World Health Organization (WHO) toxicity criteria. RESULTS: Of all 40 patients (32 men, 8 women; age range 37 to 73 years; median 63 years), 3S patients were assessable for response. 15 patients had stage IIIb disease and 25 had stage IV. Nineteen patients were histologically classified as adenocarcinoma (47.5%), 17 as squamous cell carcinoma (42.5%), 1 as large cell carcinoma (2.5%), 1 as mixed carcinoma (2.5%) and 2 as undifferentiated carcinoma (5.0%). The overall response rate was 20%. None of the patients showed complete response while 7 showed partial response (20%), 5 had stable diseases (23%) and 23 had progressive diseases (57%). During a total of 119 courses, hematologic toxicity was negligible. Granulo- cytopenia worse than WHO grade 3 occured in 11.8%, anemia in O.S% and thrombocytopenia in 0.8%, respectively. Non-hematologic toxicity was minor and easily controlled. There was no case of febrile neutropenia or treatment-related death. CONCLUSION: The single agent efficacy of gemcitabine is comparable to other agents commonly used to treat NSCLC. Gemcitabine has unusually mild side effect profile for such an active agent. This significant activity in conjunction with a very favorable toxicity profile supports further investigation in combination with other agents in patients with inoperable NSCLC.

The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma / 대한암학회지

PURPOSE: Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy. MATERIALS AND METHODS: Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. RESULTS: Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care. CONCLUSION: Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.

Acute Myocardial Infarction in the Young Adult

BACKGROUND: Myocardial infarction in young adults may differ from that in the elderly is terms of clinical characteristics and angiographic findings. The aim of this study was to evaluate the prevalence of various risk factors ; also, coronary angiographic characteristics of acute myocardial infarction in patient under 40 years old were compared to that in patient over 40 years old. METHODS: We studied 239 patients with acute myocardial infarction who were admitted to Wonju Christian Hospital from 1990 to 1995 and evaluated the clinical and coronary angiographic characteristics. RESULTS: The incidence of acute myocardial infarction in patients under 40 years old was 10.8% (26/239) and were predominently. In men, risk factor analysis revealed the followings ; hypertension was more frequent in elderly patients, and in contrast, smoking history was more frequent in younger patients. Other risk factors did not significantly differ between the two groups. Normal coronary artery was more frequent in the younger patients. The diameter stenosis of the infarct related artery was also less servere in the younger patients. In-hospital morbidity and mortality were not significantly different between the two groups. CONCLUSIONS: Men and smokers were predominent in patients with acute myocardial infarction under 40 years old. The vessel involvement and the diameter stenosis of infarct related artery were less servere in patients with acute myocardial infarction under 40 years old than patients over 40 years old.

Microsatellite Instability Correlate with a Prognosis in Breast Cancer / 대한암학회지

PURPOSE: Microsatellite instability in patients with defects in the mismatch repair system resulting in RER has a high risk of accumulating mutations in oncogene and tumor suppressor gene. In this study, we evaluated the incidence of microsatellite instability in breast cancer by comparing PCR-amplified sequences from frozen samples of normal and tumor tissue fram affected patients. We also investigated whether RER was associated with TGF-beta RII mutation. MATERIALS AND METHODS: Fifty surgically resected breast cancer specimens from Jan. 1996 to June, 1997 were used for study. Microsatellite instability(referred to as replication error, RER) at three loci with BAT 26, BAT 40, TA10 was analyzed by polymerase chain reaction and the results were compared with clinicopathologic characteristics. RESULTS: Of the 50 breast cancer patients, 14(28%) were RER(+) at one or more microsatellite loci, and 4(8%) showed TGF-beta RII mutation. Microsatellite instability was significantly correlated with lymph node involvement(especially in case of 4 or more lymph nodes involvement). But we could not find any correlation between RER and other prognostic factors including tumor size, tumor grade, hormone receptor status and pathology. One of fourteen tumors with RER(+) showed TGF-beta RII mutstion. There was no signiticant correlation between RER(+) and TGF-beta type II receptor gene mutation. CONCLUSION: The findings suggest that microsatellite instability would be useful prognostic factor in unilateral breast cancer patients, and the role of targeting to gene mutation will be explored in future studies.