Transcriptomic Analysis of Papillary Thyroid Cancer: A Focus on Immune-Subtyping, Oncogenic Fusion, and Recurrence

Objectives@#. Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. @*Methods@#. This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. @*Results@#. Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). @*Conclusion@#. We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

The current status of cancer survivorship care and a consideration of appropriate care model in Korea

Purpose@#Breast cancer patients with a human epidermal growth factor receptor 2 (HER2) enriched subtype are known to have higher rates of brain metastases (BM) than other patients. This study aimed to evaluate treatment options and survival outcomes. @*Methods@#A total of 115 breast cancer brain metastases (BCBM) patients with nearly complete medical records were retrospectively analyzed. Additionally, 36 patients were HER2 enriched types according to histological subtypes. The BM was found by brain magnetic resonance imaging in patients who had neurologic symptoms or by regular screening. Age, breast tumor size, number of BM, histological subtypes, first treatment of breast cancer, estrogen receptor, and HER2 status, stage, local treatment of BM were analyzed. Median overall survival, 5-year survival were analyzed from the data. @*Results@#The median survival time after BM was 6 months, the mean survival time was 16.3 months, and the 5-year survival after BM was only 8.0%. Factors that significantly affect the survival of BCBM patients include histological subtype, number of BM, use of lapatinib in multivariate analysis. A total of 19 out of 36 HER2 enriched patients were treated with lapatinib or capecitabine. For the treatment of HER2 enriched patients, additional use of blood-brain barrier (BBB) crossing substances, as well as local treatment for BM, significantly improve the survival rate in the Kaplan-Meier method (P=0.001). @*Conclusion@#A combination of local treatment modality for BCBM and the use of substances that cross the BBB for the HER2 enriched patient improved the survival rate.

The current status of cancer survivorship care and a consideration of appropriate care model in Korea

Purpose@#Breast cancer patients with a human epidermal growth factor receptor 2 (HER2) enriched subtype are known to have higher rates of brain metastases (BM) than other patients. This study aimed to evaluate treatment options and survival outcomes. @*Methods@#A total of 115 breast cancer brain metastases (BCBM) patients with nearly complete medical records were retrospectively analyzed. Additionally, 36 patients were HER2 enriched types according to histological subtypes. The BM was found by brain magnetic resonance imaging in patients who had neurologic symptoms or by regular screening. Age, breast tumor size, number of BM, histological subtypes, first treatment of breast cancer, estrogen receptor, and HER2 status, stage, local treatment of BM were analyzed. Median overall survival, 5-year survival were analyzed from the data. @*Results@#The median survival time after BM was 6 months, the mean survival time was 16.3 months, and the 5-year survival after BM was only 8.0%. Factors that significantly affect the survival of BCBM patients include histological subtype, number of BM, use of lapatinib in multivariate analysis. A total of 19 out of 36 HER2 enriched patients were treated with lapatinib or capecitabine. For the treatment of HER2 enriched patients, additional use of blood-brain barrier (BBB) crossing substances, as well as local treatment for BM, significantly improve the survival rate in the Kaplan-Meier method (P=0.001). @*Conclusion@#A combination of local treatment modality for BCBM and the use of substances that cross the BBB for the HER2 enriched patient improved the survival rate.

An Unusual Case of Metastatic Non-Small Cell Lung Cancer Misidentified as Anaplastic Thyroid Cancer

Metastases from other organs to the thyroid are considered to be extremely rare. Among thyroid malignancies, anaplastic thyroid cancer exhibits similar features to a number of other cancers and can therefore be easily misdiagnosed. In addition to the fine needle aspiration commonly used for assessing thyroid lesions, metastatic tumors and primary thyroid cancers can be distinguished through approaches such as immunohistochemistry, taking into consideration the possibility of other primary cancers. Here, we present a case of metastatic non-small cell lung cancer that was misidentified as anaplastic thyroid cancer and discuss its diagnosis and treatment.

Assessment of Quality of Life and Safety in Postmenopausal Breast Cancer Patients Receiving Letrozole as an Early Adjuvant Treatment / 한국유방암학회지

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from −0.39 at baseline to −0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.

Predictive factors of central lymph node metastasis in papillary thyroid carcinoma

PURPOSE: The aim of this study was to evaluate the correlation between central lymph node (CLN) metastasis and clinicopathologic characteristics of papillary thyroid cancer (PTC). In addition, we investigated the incidence and risk factors for contralateral CLN metastasis in unilateral PTC. This study suggests the appropriate surgical extent for CLN dissection. METHODS: A prospective study of 500 patients with PTC who underwent total thyroidectomy and prophylactic bilateral CLN dissection was conducted. RESULTS: Of 500 patients, 255 had CLN metastases. The rate of CLN metastasis was considerably higher in cases of younger patients ( or =1 cm) (P = 0.019; OR, 4.440) and with ipsilateral CLN metastasis (P = 0.047; OR, 2.613). CONCLUSION: Younger age (<45 years old) and maximal tumor size greater than 1 cm were independent risk factors for CLN metastasis. Maximal tumor size greater than 1 cm and presence of ipsilateral CLN macrometastasis were independent risk factors for contralateral CLN metastasis. Therefore, both CLN dissections should be considered for unilateral PTC with a maximal tumor size greater than 1 cm or presence of ipsilateral CLN macrometastasis.

Prediction of Nodal Metastasis by the AMES Scoring System in Patients with Papillary Thyroid Cancer / 대한내분비외과학회지

PURPOSE: We assessed the prognostic value of AMES to determine the extent of surgery in PTC patients, and compared AMES score usefulness and accuracy with [18F] FDG PET/CT. METHODS: We conducted a review of data from a single center and a single surgeon, who treated 341 patients with PTC with total thyroidectomy and prophylactic bilateral CLN dissection at a tertiary referral center, Chungnam National University Hospital, between 2001 and 2012. RESULTS: In multivariate analysis, the rate of CLN metastasis was considerably higher in PTC patients with the higher AMES score (odds ratio [OR], 1.718; 95% confidence interval [CI], 1.073~2.752), higher SUV of the CLN (>0) (OR, 6.525; CI, 3.184~13.371), higher SUV of the tumor (>4.3) (OR, 1.855; CI, 1.065~3.231). CONCLUSION: The AMES score is helpful in deciding whether to perform a CLN dissection, as there is a strong association between the AMES score and CLN metastasis. This high predictive value of CLN metastasis can help determine the extent of PTC surgery while considering the cost and effort.

Medullary and Papillary Thyroid Carcinoma as a Collision Tumor: Report of Five Cases / 대한내분비외과학회지

Medullary thyroid carcinoma and papillary thyroid carcinoma are different subtypes of thyroid carcinoma. The concomitant occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma as a collision tumor is rare. We describe five cases of medullary and papillary thyroid carcinoma as a collision tumor. Four women and one man underwent thyroidectomy for treatment of thyroid cancer. Collision tumor was then detected by histopathologic finding. Genetic testing, point mutation of the BRAF gene or mutation of the RET gene was performed in three cases. However, only one case had point mutation of the BRAF gene. Exact diagnosis of this uncommon event is important because the strategies for treatment of papillary thyroid carcinoma and medullary thyroid carcinoma are different.

Survey of the Application of the Korean Clinical Practice Recommendations on Breast Cancer Treatment: The Utility of the Korean Breast Cancer Society Guidelines / 한국유방암학회지

This survey was performed to analyze the usability of the third edition of the Korean breast cancer clinical practice guidelines (KBCCPG) in clinical practice. We made a questionnaire composed of 18 general and 82 specific questions regarding benign breast disease (B; 1 question); non-invasive disease (N; 12 questions); early-stage disease (E; 26 questions); advanced disease (A; 24 questions); and metastatic (M) breast cancer-related problems (19 questions). A total of 100 questionnaires, with a link to an online survey, were delivered via e-mail to over 700 members of the Korean Breast Cancer Society (KBCS), and associated academy members, over 20 days between 26th February and 16th May 2010. Out of 270 respondents who read the e-mail, 96 answered the questionnaire. Participants included 87 surgical oncologists, 5 radiation oncologists, 2 oncoplastic surgeons, 1 pathologist, and 1 medical oncologist. The third KBCCPG were perceived as differing from the second guidelines in terms of the level of clinical evidence required before choosing a recommendation. For the progress of the KBCCPG, the guideline committee should try to reinforce all courses of guideline development with several elements including data from clinical trials of Korean breast cancer patients, securing a multidisciplinary approach, developing consistent and reasonable processes for each step of the revision of the guidelines, induction of liberal scientific and ethical discussion about all issues with all KBCS members. The cost-effectiveness of healthcare and the logical development of the KBCCPG would also be ensured. Timely updates of the clinical guidelines for breast cancer treatment are essential to facilitate optimal decision-making in daily practice, and to ensure adequate patient feedback.

Mutation-Free Expression of c-Kit and PDGFRA in Phyllodes Tumors of the Breast / 한국유방암학회지

PURPOSE: Phyllodes tumors (PTs) of the breast have been classified as benign, borderline, or malignant based on their histopathologic features. However, predicting clinical behavior based on these features has proven to be difficult given that local recurrence occurs in both benign and malignant PTs. Recurrence has been shown to mirror the histologic pattern of the primary tumor or to show dedifferentiation. The aim of this study was to assess the value of the histopathologic parameters, expression or mutation of c-Kit and platelet derived growth factor receptor alpha (PDGFRA) in predicting tumor recurrence. METHODS: Representative areas from 39 benign, 16 borderline, and 12 malignant PTs were selected for construction of tissue microarrays. Immunohistochemical analyses for p53, Ki-67, c-Kit, and PDGFRA were performed and SSCP-PCR analysis was carried out to identify mutations in exons 9, 11, 13, and 17 of the c-Kit gene and exons 12 and 18 of the PDGFRA gene. Clinicopathologic features, including tumor recurrence and margin status, were also evaluated. RESULTS: Of the 67 PTs, 11 cases (16.4%) recurred from 3 to 92 months following initial diagnosis (4 benign, 2 borderline, and 5 malignant). One benign PT case recurred as a borderline tumor and two borderline PT cases recurred as malignancies. Three patients died of malignant PT. No mutations of the c-Kit or PDGFRA genes were found and there was no statistically significant association of either p53 or p16 immunostaining with recurrent disease (p>0.05). However, histologic grade (p=0.033), margin status (p<0.001), Ki-67 (p=0.012), c-Kit (p=0.002), and PDGFRA (p=0.007) stromal immunopositivity were significantly correlated with recurrence. CONCLUSION: Even though positive or close margins were significantly associated with tumor recurrence, stromal c-Kit, PDGFRA positivity, and the Ki-67 index were useful for predicting recurrent PTs. Despite this, no c-Kit or PDGFRA mutations were found.

A Comparison of the Usefulness and Safety of the Harmonic™ Scalpel, Ligasure™ System, and Classic Clamp-and-Tie Technique for Hemostasis during Thyroid Surgery / 대한내분비외과학회지

PURPOSE: The aim of this study was to compare the outcome of total thyroidectomy performed with the Ligasure™ system, Harmonic™ scalpel, and the conventional clampand-tie technique. METHODS: Between November 2006 and July 2009, the data were retrospectively collected from 600 consecutive total thyroidectomies by one surgeon. All cases were divided into 3 groups based on the method of hemostasis: classic group patients (n=200) underwent total thyroidectomy with the conventional clamp-and-tie technique Ligasure group patients (n=200) underwent total thyroidectomy with the Ligasure™ system (electrothermal bipolar vessel sealing system) and the Harmonic group patients (n=200) underwent total thyroidectomy with a Harmonic™ scalpel (ultrasonic cutting and coagulating surgical device). We compared the clinical outcomes with respect to the operative time, amount and duration of drainage, hospital stay, and post-operative complications. RESULTS: The three groups were similar with respect to clinical and demographic characteristics, with the exception of invasiveness. The mean operative time of the Harmonic group was significantly shorter than the other 2 groups (P<0.001) specifically, 75 min in the Harmonic group, 87 min in the Ligasure group, and 120 min in the classic group. The amount of drainage in the Harmonic group was greater than the other groups (P<0.001). Similarly, the duration of drainage and hospital stay of the Harmonic group were longer than the other groups. There was no significant difference in the incidence of complications between the three groups. CONCLUSION: Hemostasis during thyroidectomy by the Harmonic™ scalpel or Ligasure™ system was safe and timesaving. Therefore, the Harmonic™ scalpel and Ligasure™ system will be available for thyroid surgery as alternative techniques for the clamp-and-tie technique.

A Comparison of Conventional Thyroidectomy and LVSS Thyroidectomy: The Feasibility of the LVSS in the Thyroid Operation

PURPOSE: Recently, Ligasure vessel sealing system (LVSS) is being introduced in thyroid operations. In this study, we compare the clinical outcomes of LVSS using thyroidectomy with those of conventional thyroidectomy. METHODS: From Nov 2006 to Oct 2008, 400 patients managed with total thyroidectomy were investigated. Half of them (the conventional group) were operated on with conventional methods, whereas another half (the LVSS group) were operated on using LVSS. Operation time, amount of drainage, duration of drainage, hospital stay, and complications (numbness, hoarseness, hematoma) of the two groups were compared. RESULTS: The mean operation time of the LVSS group was 87.53+/-27.49 (min), and that of the conventional group was 120.48+/-39.51 (min). Therefore, operation times of the LVSS group was significantly shorter than that of the conventional group (P<0.001). But, there was no significant difference in the amount of drainage, duration of drainage, duration of hospital stay, and the incidences of complications. CONCLUSION: Our studies show the effectiveness and safety of LVSS in thyroid operations. We advocate the application of LVSS to thyroid operations.

Preoperative Axillary Staging Using 18F-FDG PET/CT and Ultrasonography in Breast Cancer Patients / 한국유방암학회지

PURPOSE: The axillary lymph node status is an important prognostic factor for recurrence and survival of patients who have primary breast cancer. This study determined the accuracy of ultrasonography and 18F-FDG positron emission tomography (PET)/computed tomography (CT) in preoperative staging in axilla in patients with breast cancer. METHODS: One hundred seventy-one patients with primary breast cancer were recruited from January 2007 to August 2008. All the patients underwent axillary ultrasonography and 18F-FDG PET/CT for the axillary staging before their operation. RESULTS: The overall sensitivity, specificity, and the positive and negative predictive values and the accuracy of axillary ultrasonography for making the diagnosis of axillary metastasis were 73.07%, 84.87%, 67.85%, 87.82%, and 81.28%, respectively. On a visual assessment of 18F-FDG PET/CT, the diagnostic accuracy was 85.38% with 69.23% sensitivity, 92.43% specificity, a positive predictive value of 80.00%, and a negative predictive value of 87.30%. By the combined use axillary ultrasonography and 18F-FDG PET/CT to the axilla, the sensitivity, specificity, the positive and negative predictive values and the diagnostic accuracy were 82.35%, 97.91%, 93.33%, 94.00%, and 93.84%, respectively. CONCLUSION: The combination of 18F-FDG PET/CT and ultrasonography improves preoperative axillary staging in breast cancer that are often not found if only one imaging modalities are applied.

(18)F-FDG PET/CT for the Preoperative Diagnosis of Papillary Thyroid Microcarcinoma: The Value of Dual Time Point Imaging / 핵의학분자영상

PURPOSE: We studied the patterns of FDG uptake of primary papillary thyroid microcarcinoma (PTMCa) lesions and benign thyroid nodules in dual time point (18)F-FDG PET/CT imaging. MATERIALS AND METHODS: Consecutive 134 patients (154 lesions) with PTMCa and 49 patients (61 nodules) with benign thyroid nodules equal to or less than 1.0 cm who underwent dual time point (18)F-FDG PET/CT study before surgery were enrolled. We calculated the maximum standardized uptake value of PTMCa and benign nodules in both time points, and percent change of SUVmax (delta%SUVmax) and lesion to background ratio of SUVmax (delta%L:B ratio) between both time points. The mean time interval between scans was 23.4+/-4.4 minutes (thyroid to thyroid interval: 10.7+/-4.4 minutes). RESULTS: The mean of SUVmax of PTMCa was increased from 4.9+/-4.3 to 5.3+/-4.7 (p<0.001) and delta%SUVmax was 12.3+/-23.6%. But, the mean of SUVmax of benign nodules was no definite change (2.1+/-1.0 to 2.1+/-1.3, p=0.686) and delta%SUVmax was -0.3+/-20.5%. Of the 154 PTMCa, 100 nodules (64.9%) showed an increase in SUVmax over time, while 19 (31.1%) of the 61 benign thyroid nodules showed an increase (p<0.001). The dual time point (18)F-FDG PET/CT found more PTMCa in visual assessment (62.3% vs. 76.6%, p=0.006), even in smaller than 0.5 cm (38.6% vs. 60.0%, p=0.011). CONCLUSION: Dual time time (18)F-FDG PET/CT imaging was more useful than single time point (18)F-FDG PET/CT imaging for distinction between PTMCa and benign nodule, especially when nodule showed equivocal or negative findings in single time point (18)F-FDG PET/CT imaging or was smaller than 0.5 cm.

Comparative Analysis of Vascular Endothelial Growth Factor-A, C, D Expression in Colorectal Cancer with Liver Metastasis

PURPOSE: We aimed to investigate the correlations between expressions of angiogenic cytokines VEGF-A, C, D of primary colorectal cancer and liver metastasis. METHODS: We examined paraffin-embedded primary colorectal cancer tissue from 45 patients who had liver resection due to colorectal liver metastasis (metastasis group) and 37 patients who had surgical resection due to colorectal cancer only (control group). In the control group, local recurrence and distant metastasis had not occurred. Immunohistochemical staining for VEGF-A, C and D was performed. We analysed the correlations between expression of VEGF-A, C and D in primary colorectal cancer tissues and clinicopathologic parameters. RESULTS: VEGF-A expressions of primary colorectal carcinoma were not different between the two groups. VEGF-C was more frequently expressed in the metastasis group (P=0.008) but VEGF-D was more expressed in the control group (P=0.003). Patients with VEGF-C negative and VEGF-D positive expression were predominant in the control group (P=0.020). Tumor location, T stage, lymph node metastasis and tumor differentiation were not related with the expressions of VEGF-A, C, D but only preoperative CEA was positively correlated with VEGF-A and C expression. CONCLUSION: Expressions of VEGF-C in primary tumor were more frequent in metastatic colorectal cancer and expressions of VEGF-D were more frequent in nonmetastatic colorectal cancer. More large-scale prospective studies for VEGF-C and D expression in colorectal cancer are necessary.

Endoscopic Thyroidectomy via an Axillo-bilateral Breast Approach: 5 Years of Experience / 대한내분비외과학회지

PURPOSE: Conventional surgery for thyroid disease requires long skin incisions and can lead to prominent scars of the neck, adhesions, hypoesthesia, and paresthesia. To overcome these problems we performed an endoscopic thyroidectomy via an axillo-bilateral breast approach. METHODS: Seventy patients with benign thyroid nodules by fine needle aspiration were selected. Patients underwent endoscopic thyroidectomy via axillo-bilateral breast approach from May, 2003, through November, 2007. RESULTS: Operations included 67 lobectomies, 1 isthmectomy, and 2 total thyroidectomies. Two cases were converted to an open thyroidectomy because of bleeding. The mean operating time was 90.6 min (range, 60~170). The mean length of hospital stay was 6.39 days (range, 4~12), and the mean duration of drainage was 3.87 days (range, 2~9). Postoperative hematoma for 3 patients was observed, but absorbed spontaneously. Two patients complained of hoarseness and 1 patient had vocal cord palsy, but these disappeared during follow-up. CONCLUSION: This approach resulted in satisfactory cosmetic results and no significant complications. We believe that endoscopic thyroidectomy via an axillo-bilateral breast approach is feasible and safe.

Dermatomyositis in a Breast Cancer Patient

Cancer-associated rheumatic disorders are sometimes present concurrently with a tumor, but are not recognized initially. We report a case of dermatomyositis with breast cancer. A 46 year-old woman diagnosed with breast cancer with axillary lymph node metastasis had been treated by neoadjuvant chemotherapy and a lumpectomy with axillary lymph node dissection. She presented with a red rash on her face, eyelids, neck, and shoulders. A skin biopsy did not rule out dermatomyositis. Laboratory values were within normal limits, except muscle enzymes (Creatine kinase). Electromyography showed the presence of early myopathy. A PET CT-scan showed muscle uptake in left infraspinatus, r/o myositis. No abnormalities were presented in the muscle biopsy. Symptoms were improved by steroid therapy.

Promoter Methylation Profiles and Its Association with Clinicopathological Features in Breast Cancer

PURPOSE: Aberrant DNA methylation of tumor suppressor genes has been accepted as a common feature and early event in human cancer. The aim of this study was to analyze the methylation profiles of 50 well established methylation-associated genes in relation to various clinico-pathological features in breast cancer. METHODS: The methylation status of 50 genes were determined in two breast cancer cell lines, MCF7 and MDA- MB231, using HpaII-MspI-PCR. 8 genes (APC, CALCA, CDH13, MTHFR, S100A2, H19, EDNRB and MUC2) were found to be methylated in at least 1 cell line. The methylation of all 8 genes was observed in tumor tissues, but with different methylation frequencies. RESULTS: The methylation frequencies of five genes in breast cancer were as follows: MTHFR (41.9%), APC (51.6%), EDNRB (77.4%), CALCA (80.6%), S100A2 (87.1%), CDH13 (93.5%), H19 (93.5%) and MUC2 (96.8%). The results indicate that a panel of these 8 genes would be useful in the detection of breast cancer. The prognostic significance of DNA methylation in this breast cancer series, the conventional markers of LN status (P=0.05), histologic grade (P= 0.007) and P53 gene status (P=0.049) showed significant prognostic value. CONCLUSION: The methylation of APC, MTHFR, CALCA, CDH13, H19, MUC2, EDNRB and S00A2 would be useful in the detection of breast cancer. Detection of these abnormalities may be useful in the risk assessment and early detection of breast cancer.

Short Term Follow-up Data in Breast Cancer Patients with Sentinel Lymph Node Biopsy Alone

PURPOSE: Sentinel lymph node (SLN) dissection is now a widely used and accepted method for staging the axilla in breast cancer patients. The aim of this study was to determine the rate of axillary lymphatic recurrence and metastasis in breast cancer patients who had a negative SLNB. METHODS: A retrospective chart review from August of 2001 to December of 2003 was performed for all patients (n=89) who underwent a SLN biopsy and they had a negative SLN on the intraoperative frozen sections. Any additional axillary lymph node dissection was not performed even when the sentinel lymph node(s) were found to be positive by the permanent pathology. The patients received appropriate adjuvant therapy according to the characteristics of the primary tumor. All the patients who had breast conserving surgery received postoperative radiotherapy to the remaining breast, but not to the axilla. RESULTS: A mean of 4.92 LNs were removed per patient. Among the 89 patients whose sentinel lymph nodes were tumor-free on frozen section, 9 patients had metastatic lymph nodes on the permanent pathology. All the metastases were micrometastasis. Over a mean follow-up period of 53 months, one patient died of liver metastasis and one patient developed n ipsilateral breast recurrence. Only one patient developed an axillary recurrence. CONCLUSION: SLNB provides accurate staging of breast cancer and this might be a good alternative to routine axillary lymph node dissection with incurring less surgical morbidity.

Capecitabine Monotherapy in Taxane-Refractory Metastatic Breast Cancer (MBC) Patients

PURPOSE: The therapeutic options for MBC patients who have been previously treated with taxane and anthracycline are limited. Capecitabine (Xeloda(R)) is a novel tumor- selective oral fluoropyrimidine, and it provides effective and well tolerated therapy for patients with MBC who are resistant to or are failing with anthracycline and taxane therapy. We present our experiences with oral capecitabine that was given as monotherapy for taxane and anthracycline pre-treated MBC patients from CNU hospital. METHODS: The study subjects were 32 female patients having MBC that progressed after anthracycline and taxane treatment, and they were then treated with oral capecitabine monotherapy from 1999 to 2002. The median disease free survival period was 26 months. All the patients had good ECOG perfomance status (>2) and normal renal function. The primary end points were the response rate, time to progression (TTP) and overall survival. The response rate was assessed with standard UICC criteria, and toxicity was assessed with NCI toxicity criteria. RESULTS: The sites of first metastasis were bone in 17 cases (53.1%); cervical LN 5 (15.6%); liver 3 (9.4%); lung 3 (9.4%); chest wall 2 (6.3%); brain 1 (3.1%); and contralateral axillary LN 1 (3.1%). The clinical response rates to therapy were 1 case of CR (3.1%); 13 cases of PR (40.6%); 11 cases of stable disease (34.4%); 6 cases of progressive disease (18.8%). The median TTP was 6.0 months (95% CI: 5.53~8.47). The median overall survival was 15.0 months (95% CI: 11.90~16.10). Toxicities related to therapy were 5 cases of hand-foot skin reaction (15.6%); 3 cases of diarrhea (9.4%); and 1 case of stomatitis (3.1%). There was no bone marrow depression or alopecia. All treatment related toxicities were improved by a short period of drug interruption or dose reduction (2, 500 mg/m2/day to 2, 000 mg/m2/day). CONCLUSION: Taxane resistant MBC has a poor prognosis. Oral capecitabine monotherapy provided activity in this subgroup of patients with an overall response rate of 43.7% and a stable disease rate of 34.4%. Oral capecitabine is well tolerated with an acceptable toxicity profile in this population.