PURPOSE: Given the promising activity of capecitabine and vinorelbine in metastatic breast cancer, this randomized phase II trial evaluated the efficacy and safety of this combination as neoadjuvant chemotherapy in breast cancer. MATERIALS AND METHODS: Patients with operable breast cancer (n=75) were randomly assigned to receive either four cycles of adriamycin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks followed by four cycles of docetaxel 75 mg/m2 every 3 weeks (AC-D) or four cycles of capecitabine 2,000 mg/m2 (day 1-14) plus vinorelbine 25 mg/m2 (days 1 and 8) every 3 weeks followed by four cycles of docetaxel 75 mg/m2 (CV-D). The primary endpoint was pathologic complete response (pCR) in the primary breast (ypT0/is). RESULTS: Most patients (84%) had locally advanced (n=41) or inflammatory breast cancer (n=22). pCR rates in the primary breast were 15% (95% confidence interval [CI], 7% to 30%) and 11% (95% CI, 4% to 26%) in the AC-D and CV-D groups, respectively. The overall response rates and 5-year progression-free survival rates in the AC-D and CV-D groups were 62% and 64%, and 51.3% (95% CI, 34.6% to 68.0%) and 30.2% (95% CI, 13.3% to 47.1%), respectively. Although both regimens were well tolerated, CV-D showed less frequent grade 3-4 neutropenia and vomiting than AC-D, whereas manageable diarrhea and hand-foot syndrome were more common in the CV-D group. CONCLUSION: CV-D is a feasible and active non-anthracycline-based neoadjuvant chemotherapy regimen for breast cancer.
Anthracyclines ; Breast ; Breast Neoplasms* ; Cyclophosphamide* ; Diarrhea ; Disease-Free Survival ; Doxorubicin* ; Drug Therapy* ; Hand-Foot Syndrome ; Humans ; Inflammatory Breast Neoplasms ; Neoadjuvant Therapy ; Neutropenia ; Polymerase Chain Reaction ; Vomiting

PURPOSE: Although most patients with stage I breast cancer have a good prognosis, their clinical outcomes may vary significantly. We assessed clinical outcomes and prognostic factors in stage I breast cancer patients with and without triple-negative breast cancer (TNBC) phenotype. METHODS: Of 2,489 patients undergoing breast cancer surgery between January 1998 and December 2002, 554 (22.3%) had stage I breast cancer (tumor size < or =2 cm, and lymph node-negative). TNBC was defined as a primary tumor negative for estrogen and progesterone receptors (Allred scores <3/8) and for HER2/neu (0-1+ by immunohistochemistry). RESULTS: Of the 554 patients with stage I breast cancer, 78 (14.1%) had TNBC. A significant proportion of TNBC patients had histologic grade 3 tumors (47.4% vs. 34.5%, p=0.031) and tumors >1 cm (87.2% vs. 75.8%, p=0.028) and received adjuvant chemotherapy (79.5% vs. 44.7%, p<0.001). During a median follow-up time of 8.7 years, 72 patients experienced tumor recurrences; 18 (23.1%) in the TNBC group and 54 (11.3%) in the non-TNBC group (p=0.010), with cumulative 3-year rate of recurrence of 12.8% and 5.3%, respectively (p=0.010). Ten-year relapse-free survival (RFS; 75.6% vs. 87.5%, p=0.004) and overall survival (OS; 83.0% vs. 91.4%, p=0.002) rates were significantly lower in the TNBC group. Multivariate analysis showed that triple negativity and histologic grade were independent predictors of shorter RFS and OS. CONCLUSION: TNBC had more aggressive clinicopathologic characteristics and was associated with poorer survival in patients with stage I breast cancer. More intensive adjuvant chemotherapy or a different therapeutic strategy targeting this population is warranted.
Breast ; Breast Neoplasms ; Chemotherapy, Adjuvant ; Estrogens ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Phenotype ; Prognosis ; Receptors, Progesterone ; Recurrence

We describe here a case of localized polyarteritis nodosa that involved the unilateral breast in a 69-yr-old woman. She presented with a tender breast mass and had suffered for two months. On physical examination, an ill-defined 2 cm sized, firm mass was palpated. Ultrasonographic examination revealed a mass like lesion that contained microcalcifications. The mass was excised because of the suspicion of carcinoma. The histologic findings were vasculitis involving medium and small sized-arteries that showed marked neutrophilic and lymphocytic infiltrations with intimal fibroplasias and fragmentation of the internal elastic lamina. The patient progressed well after surgical excision. The discussion includes the importance of differential diagnosis between localized polyarteritis nodosa and other vasculitis, and review of previously reported cases of vasculitis of the breast. Only 13 cases of polyarteritis nodosa of the breast have been reported and this is the first case of polyarteritis nodosa with mammary duct ectasia.
Breast* ; Diagnosis, Differential ; Dilatation, Pathologic* ; Female ; Humans ; Neutrophils ; Physical Examination ; Polyarteritis Nodosa* ; Vasculitis

BACKGROUND: Compared with common well-differentiated thyroid carcinomas, the genetic alterations underlying the development and progression of anaplastic thyroid carcinomas(ATC) are still uncharacterized. Comparative genomic hybridization(CGH) is a cytogenetic technique that can identify gains and losses in the DNA sequence copy number in tumors. METHODS: The authors studied the changes in the DNA copy number due to CGH in paraffin-embedded tissue blocks of 17 ATC cases, and tried to ascertain whether the genomic changes correlate with the clinicopathological parameters including patients' age, sex, primary tumor size, lymphovascular invasion, extrathyroid extension, regional node metastasis and immunohistochemical expression of cyclin D1. RESULTS: Fourteen of the 17 samples(82.4%) showed chromosomal changes, with a mean number of gains or losses per carcinoma of 3.6(range 2~6; 30 gains and 21 losses). The most frequently detected imbalance was the gain of chromosome 1q, which was seen in 35.7% of cases, particularly commonly in ATC associated with a papillary thyroid carcinoma. Other commonly occurring gains were present in 11q13 and 19(28.6%, respectively). Genomic amplification was detected in all four cases showing the 11q13 gain. Genomic losses were commonly noted in 3q, 6q, 18q andchi(21.4%, respectively). When numerical CGH alterations were compared to the clinicopathological parameters, there were no significant correlations(P>0.05). Cyclin D1 expression was noted in sixteen of the 17 cases(94.1%), but the extent of cyclin D1 expression was not correlated with the numerical CGH alterations(P>0.05). CONCLUSION: Taken together, the aberrations of 1q, 3q, 6q, 11q13 and 18q are relatively common in ATC, and may play an important role it developement. These findings should lead to the characterization of tumor suppressor genes and oncogenes that are potentially involved in the carcinogenesis of ATC. The amplification of 11q13 is characteristically found, but cyclin D1 in this region may be innocent of the aggressiveness of these carcinomas.
Base Sequence ; Carcinogenesis ; Comparative Genomic Hybridization* ; Cyclin D1 ; Cytogenetic Analysis ; DNA ; Genes, Tumor Suppressor ; Neoplasm Metastasis ; Oncogenes ; Thyroid Gland* ; Thyroid Neoplasms*

PURPOSE: This study was conducted to investigate whether breast cancer with p53 protein overexpression (p53+) and loss of p16 protein expression (p16-) shows different body size indicator (height, weight, body mass index) associations as compared with breast tumors without p53 protein overexpression and the loss of p16 expression (p53-, p16+). MATERIALS AND METHODS: A hospital based case-control study was conducted among 92 women patients and 122 control subjects. The p53 protein overexpression and loss of p16 protein expression in the tissue sections of patients with breast cancer were determined using immunohistochemistry. RESULTS: A total of 26 tumors (28%) demonstrated p53 overexpression and 35 tumors (46%) showed abnormal p16 expression. The heaviest women had a higher risk with p53- and p16+ breast tumors. The odds ratios (OR) adjusted for age, menopausal status, smoking, and drinking revealed a significant gradient of increasing risk of breast cancer with increasing BMI in p53- and p16+ breast cancer. The adjusted ORs for the highest quintile of BMI was 8.51 with p53+ tumors and 14.2 with p53- tumors, and 55.6 with p16+ tumors and 3.72 with p16- tumors. p53 protein overexpression and the loss of p16 expression did not significantly correlate with nodal status, tumor size, estrogen or progesterone receptor status. CONCLUSION: The study concluded that a strong association between p53-/p16+ tumors and BMI suggests the occurrence of p53-/p16+ tumors is related with obesity as compared to p53-/p16+ tumors.
Body Mass Index* ; Body Size ; Body Weight ; Breast Neoplasms* ; Breast* ; Case-Control Studies ; Drinking ; Estrogens ; Female ; Humans ; Immunohistochemistry ; Obesity ; Odds Ratio ; Receptors, Progesterone ; Smoke ; Smoking

PURPOSE: This prospective study was performed to evaluate the usefulness of preoperative radioimmu-noscintigraphy and intraoperative scintimetric examination (radioimmunoguided surgery: RIGS) using (99m)Tc-anti-CEA F(ab')(2), fragment. MATERIALS AND METHODS: Nineteen patients with rectal cancer underwent preoperative whole body planar scintigraphy at 4 hours after injection of (99m)Tc-anti-CEA F(ab')(2), fragment and SPECT imaging at 18 hours. Surgical operation was performed at 24 hours after injection. During laparotomy, radioactivities from intraabdominal viscera were measured by gamma probe. The radioac-tivities from excised tumor and lymph nodes were also measured and compared with pathology. RESULTS: All nineteen patients were confirmed to have adenocarcinomas in the rectum. Twenty-seven of 97 excised lymph node groups had metastasis and 2 patients had liver metastasis in pathology. Preoperative radioim- munoscintigraphy detected primary tumors in 11 patients (sensitivity 55%) and it couId not detect any lymph nodes or liver metastasis. All patients showed high radioactivity in the kidneys, liver, spleen, and major vessels in intraoperative measurement by gamma probe, and tumor activity was not discriminated from background activity. However, ra4ioactivity from excised tumor was higher than normal rectum (T/B ratio; 3.47+/-2.25). When excised lymph node activity/background activity ratio > 1,5 was considered as positive criteria of metastasis, sensitivity, specificity, positive and negative predictive values were 78.6%, 73.9%, 55.0% and 89.5%, respectively. CONCLUSION: Radioimmunoscintigraphy using (99m)Tc-anti-CEA F(ab')(2). has no additional value for preoperative staging and use of early RIGS using (99m)Tc-anti-CEA F(ab')(2)is inappropriate. For early RIGS using (99m)Tc labeled antibodies in rectal cancer patients, further development of more specific antibodies and methods to reduce background activity are needed.
Adenocarcinoma ; Antibodies ; Humans ; Kidney ; Laparotomy ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Pathology ; Pilot Projects* ; Prospective Studies ; Radioactivity ; Radioimmunodetection* ; Radionuclide Imaging ; Rectal Neoplasms* ; Rectum ; Sensitivity and Specificity ; Spleen ; Tomography, Emission-Computed, Single-Photon ; Viscera

BACKGROUND: In our previous study, the prevalence of the known causes of thyroid tumorigenesis was relatively rare in Korean population, suggesting genetic and environmental differences exist. Screening of genetic alteration in papillary thyroid carcinoma(PTC) and follicular adenoma(FA) in whole genomic scale was needed prior to search on individual genes of possible causes. METHODS: Ten cases of PTC without ret/PTC-I, -2, -3 rearrangement and 5 cases of follicular adenoma were included in the study of microsatellite marker allelotyping. Sixty two microsatellite markers available, were chosen to cover the known sites of loss of heterozygosity(LOH) involved in thyroid tumors, tumor suppressor genes and terminal portion of each chromosomes. PCR was performed on tumor DNA and leukocytes DNA from each patient with MDE gel electrophoresis to detect LOH. Same specitnens as above, 3 case of normal thyroid tissues and NPA, ARO cell lines were included in the study of comparative genomic hybridization(CGH). Tumor and control DNAs were hybridized to metaphase chromosome with differential stainings with fluorescein and rhoda-mine-dUTP. Obtained results were analyzed by multicolor fluorescence computer assisted image analyzer. RESULTS: In allelotyping, LOH were detected in 5 cases of PTC, 2 cases on D10S1435, 1 case each on D2S1780, DSS1099, D11S1986, D16S539, 1 case of PTC revealed LOH on DSS1099, D11S1986. In FA, LOH were detected in 3 cases on D1S534, D1S226, Dl 1S907, D22S683, DXS9807. In CGH, Xp addition was noticed in 1 case of PTC, 12q and 10p addition was noticed in 1 case each, 16q deletion and 17q addition in 1 case of FA. CONCLUSION: No hot spot of LOH was noticed in microsatellite marker allelotyping, neither of common chromosomal change in CGH study suggesting unbalanced translocation or gene amplification more than 5-10 Mb may be involved in the genetic alteration of PTC and FA.
Adenoma* ; Carcinogenesis ; Cell Line ; Comparative Genomic Hybridization ; DNA ; Electrophoresis ; Fluorescein ; Fluorescence ; Gene Amplification ; Genes, Tumor Suppressor ; Humans ; Leukocytes ; Mass Screening ; Metaphase ; Microsatellite Repeats ; Polymerase Chain Reaction ; Prevalence ; Thyroid Gland* ; Thyroid Neoplasms*

PURPOSE: Axillary lymph node metastases (ALNM) are the most important prognostic indicator in breast carcinoma. Because of relatively low incidence of axillary metastasis in the patients with Tl breast carcinoma, axillary lymph node dissection is now no longer considered to be the standard treatment. A reliable prediction of ALNM.may reduce the need for axillary lymph node dissection and may facilitate to select appropriate treatment modality. We have attempted to identify histopathologic/immunohistochemical factors correlated with ALNM in the patients with Tl breast carcinoma. MATERIAL AND METHODS: Forty-one patients with Tl breast carcinoma who underwent modified radical mastectomy and axillary dissection between January 1993 and February 1999 were studied. We investigated the relationship between ALNM and the histopathologic/immunohistochemical factors (size, lymphatic-vascular invasion (LVI), histologic grade, age, estrogen receptor (ER) status, progesterone receptor (PR) status, p53 protein, cathepsin D (CD), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)- B 2, and microvessel density (MVD)). RESULTS: Fourteen (34.2%) out of the 41 patients with Tl breast carcinoma had ALNM. There are five statistically significant factors correlated with ALNM; lymphatic-vascular invasion (P=0.002), histologic grade (P 0.047), immunohistochemical expression of CD (P=0.005) and TGF- B 2 (P=0.004), and microvessel density (P=0.002). CONCLUSION: The histopathologic/immunohistochemical features of the primary breast tumor, such as LVI, increase in MVD, TGF- B 2 and CD expression, and histologic grade might be useful predictors of ALNM in patients with Tl breast carcinoma.
Breast Neoplasms* ; Breast* ; Cathepsin D ; Estrogens ; Fibroblast Growth Factor 2 ; Humans ; Incidence ; Lymph Node Excision ; Lymph Nodes* ; Mastectomy, Modified Radical ; Microvessels ; Neoplasm Metastasis* ; Receptors, Progesterone ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A

The origins of medullary carcinoma and papillary carcinoma of thyroid are embryologically different. We report a case of simultaneous occurrence of medullary carcinoma and papillary carcinoma of the thyroid in the same thyroid gland. In this case, the occurrence of the two tumors may be a coincidence, does not have embryological or genetical significance.
Carcinoma, Medullary ; Carcinoma, Papillary* ; Thyroid Gland*

We report a case of somatostatinoma, which manifested as insulinoma after liver metastasis. A 74-year-old man suffered from diabetes mellitus and jaundice. The abdominal CT scan of this patient showed a mass in the pancreas head, which obstructed biliary duct. He underwent Whipples procedure. Immunohistochemical staining of postoperative specimen disclosed that this tumor was strongly positive for somatostatin. After 4 months, follow up CT scan showed multiple metastatic lesions in the liver. We performed transarterial chemoinfusion two times, but the response was disappointing. After 2 months, he suffered from altered mentality, which was relieved by intake of sugar. Biochemical laboratory findings and immunohistochemical staining of liver biopsy disclosed that the metastatic lesion in this patient was insulinoma. We performed embolization of hepatic artery with gelform. The biochemical response was dramatic, but he died of septic shock, which was caused by gas forming liver abscess. In summary, we report a case of somatostatinoma which manifested as insulinoma after metastasis to the liver.
Aged ; Biopsy ; Diabetes Mellitus ; Follow-Up Studies ; Head ; Hepatic Artery ; Humans ; Insulinoma* ; Jaundice ; Liver Abscess ; Liver* ; Neoplasm Metastasis ; Pancreas ; Shock, Septic ; Somatostatin ; Somatostatinoma* ; Tomography, X-Ray Computed