Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 18 de 18
Filter
1.
Cancer Res Treat ; 47(1): 26-33, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25327493

ABSTRACT

PURPOSE: Tumor response to neoadjuvant chemotherapy (NAC) may adversely affect the identification and accuracy rate of sentinel lymph node biopsy (SLNB). This study was conducted to evaluate the feasibility of SLNB in node-positive breast cancer patients with negative axillary conversion after NAC. MATERIALS AND METHODS: Ninety-six patients with positive nodes at presentation were prospectively enrolled. (18)Fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET) and ultrasonography were performed before and after NAC. A metastatic axillary lymph node was defined as positive if it was positive upon both (18)F-FDG PET and ultrasonography, while it was considered negative if it was negative upon both (18)F-FDG PET and ultrasonography. RESULTS: After NAC, 55 cases (57.3%) became clinically node-negative, while 41 cases (42.7%) remained node-positive. In the entire cohort, the sentinel lymph node (SLN) identification and false-negative rates were 84.3% (81/96) and 18.4% (9/49), respectively. In the negative axillary conversion group, the results of SLNB showed an 85.7% (48/55) identification rate and 16.7% (4/24) false-negative rate. CONCLUSION: For breast cancer patients with clinically positive nodes at presentation, it is difficult to conclude whether the SLN accurately represents the metastatic status of all axillary lymph nodes, even after clinically negative node conversion following NAC.

2.
Yonsei Med J ; 55(5): 1187-95, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25048474

ABSTRACT

PURPOSE: The prognosis of breast cancer has been consistently improving. We analyzed our cohort of breast cancer patients with a long-term follow up at a single center over time. MATERIALS AND METHODS: A total of 1889 patients with known cancer stages were recruited and analyzed between January 1991 and December 2005. Patients were classified according to the time periods (1991-1995; 1996-2000; 2001-2005). To determine intrinsic subtypes, 858 patients whose human epidermal growth receptor-2 status and Ki67 were reported between April 2004 and December 2008 were also analyzed. RESULTS: At a median follow up of 9.1 years, the 10-year overall survival (OS) rate was 80.5% for the entire cohort. On multivariate analysis for OS and recurrence-free survival (RFS), the time period was demonstrated to be a significant factor independent of conventional prognostic markers. In the survival analysis performed for each stage (I to III), OS and RFS significantly improved according to the time periods. Adoption of new agents in adjuvant chemotherapy and endocrine therapy was increased according to the elapsed time. In the patients with known subtypes, OS and RFS significantly differed among the subtypes, and the triple-negative subtype showed the worst outcome in stages II and III. CONCLUSION: In the Korean breast cancer cohort with a long-term follow up, our data show an improved prognosis over the past decades, and harbor the contribution of advances in adjuvant treatment. Moreover, we provided new insight regarding comparison of the prognostic impact between the tumor burden and subtypes.


Subject(s)
Breast Neoplasms/epidemiology , Disease-Free Survival , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Multivariate Analysis , Prognosis , Republic of Korea , Survival Analysis , Survival Rate , Time Factors
3.
Yonsei Med J ; 55(3): 558-62, 2014 May.
Article in English | MEDLINE | ID: mdl-24719119

ABSTRACT

PURPOSE: Liver resection with colorectal liver metastasis widely accepted and has been considered safe and effective therapeutic option. However, the role of liver resection in breast cancer with liver metastasis is still controversial. Therefore, we reviewed the outcome of liver resection in breast cancer patients with liver metastases in a single hospital experiences. MATERIALS AND METHODS: Between January 1991 and December 2006, 2176 patients underwent breast cancer surgery in Gangnam Severance Hospital. Among these patients, 110 cases of liver metastases were observed during follow-up and 13 of these patients received liver resection with potential feasibility to achieve an R0 resection. RESULTS: The median time interval between initial breast cancer and detection of liver metastasis was 62.5 months (range, 13-121 months). The 1-year and 3-year overall survival rates of the 13 patients with liver resection were 83.1% and 49.2%, respectively. The 1-year and 3-year overall survival rates of patients without extrahepatic metastasis were 83.3% and 66.7% and those of patients with extrahepatic metastasis were 80.0% and 0.0%, respectively (p=0.001). CONCLUSION: Liver resection for metastatic breast cancer results in improved patient survival, particularly in patients with solitary liver metastasis and good general condition.


Subject(s)
Breast Neoplasms/complications , Breast Neoplasms/surgery , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Adult , Breast Neoplasms/mortality , Female , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
4.
PLoS One ; 8(10): e79014, 2013.
Article in English | MEDLINE | ID: mdl-24205362

ABSTRACT

Anti-epidermal growth factor receptor (EGFR) therapy has been tried in triple negative breast cancer (TNBC) patients without evaluation of molecular and clinical predictors in several randomized clinical studies. Only fewer than 20% of metastatic TNBCs showed response to anti-EGFR therapy. In order to increase the overall response rate, first step would be to classify TNBC into good or poor responders according to oncogenic mutation profiles. This study provides the molecular characteristics of TNBCs including EGFR gene copy number changes and mutation status of EGFR and KRAS gene in Korean TNBC patients. Mutation analysis for EGFR, KRAS, BRAF and TP53 from a total of 105 TNBC tissue samples was performed by direct sequencing, peptide nucleic acid-mediated PCR clamping method and real-time PCR. Copy number changes of EGFR gene were evaluated using multiplex ligation-dependent probe amplification. Out of all 105 TNBCs, 15.2% (16/105) showed EGFR copy number changes. Among them, increased or decreased EGFR copy number was detected in 13 (5 single copy gain, 2 amplification and 4 high-copy number amplification) and 3 cases (3 hemizygous deletion), respectively. The mutation frequencies of KRAS, EGFR and TP53 gene were 1.9% (G12V and G12D), 1.0% (exon 19 del) and 31.4%, respectively. There was no BRAF V600E mutation found. Future studies are needed to evaluate the clinical outcomes of TNBC patients who undergo anti-EGFR therapy according to the genetic status of EGFR.


Subject(s)
ErbB Receptors/genetics , Proto-Oncogene Proteins/genetics , Triple Negative Breast Neoplasms/genetics , ras Proteins/genetics , Adult , Aged , DNA Copy Number Variations , DNA Mutational Analysis , Female , Gene Dosage , Humans , Middle Aged , Multivariate Analysis , Prognosis , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras) , Republic of Korea , Tumor Suppressor Protein p53/genetics
5.
Breast Cancer Res Treat ; 141(1): 89-99, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23933800

ABSTRACT

Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.


Subject(s)
Amino Acid Oxidoreductases/analysis , Breast Neoplasms/chemistry , Carcinoma/chemistry , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/analysis , Adult , Amino Acid Oxidoreductases/biosynthesis , Amino Acid Oxidoreductases/genetics , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma/genetics , Carcinoma/mortality , Carcinoma/pathology , Carcinoma in Situ/chemistry , Carcinoma in Situ/genetics , Carcinoma in Situ/mortality , Carcinoma in Situ/pathology , Cell Line, Tumor , Cell Movement , Collagen , Disease-Free Survival , Drug Combinations , Epithelial-Mesenchymal Transition , Female , Humans , In Situ Hybridization , Kaplan-Meier Estimate , Laminin , Middle Aged , Neoadjuvant Therapy , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Neoplasms, Multiple Primary/chemistry , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/mortality , Neoplasms, Multiple Primary/pathology , Phyllodes Tumor/chemistry , Phyllodes Tumor/genetics , Phyllodes Tumor/mortality , Phyllodes Tumor/pathology , Prognosis , Proportional Hazards Models , Proteoglycans , RNA Interference , RNA, Small Interfering/pharmacology , Survival Analysis , Tissue Array Analysis , Triple Negative Breast Neoplasms/chemistry , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology
6.
Yonsei Med J ; 54(5): 1168-77, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23918566

ABSTRACT

PURPOSE: Bone is the most frequent site of metastasis among breast cancer patients. We investigated prognostic factors affecting survival following bone-only metastasis in breast cancer patients. MATERIALS AND METHODS: The medical records of breast cancer patients who were treated and followed at Gangnam Severance Hospital retrospectively reviewed to identify patients with bone-only metastasis. RESULTS: The median time from the diagnosis of bone-only metastasis to the last follow-up or death was 55.2 [95% confidence interval (CI), 38.6-71.9] months. The Kaplan-Meier overall survival estimate at 10 years for all patients was 34.9%. In the multivariate Cox regression model, bisphosphonate treatment [hazard ratio=0.18; 95% CI, 0.07-0.43], estrogen receptor positivity (hazard ratio=0.51; 95% CI, 0.28-0.94), and solitary bone metastasis (hazard ratio=0.32; 95% CI, 0.14-0.72) were significantly associated with longer overall survival in the bone-only recurrence group. Among the treatment modalities, only bisphosphonate treatment was identified as a significant prognostic factor. CONCLUSION: Identifying the factors influencing breast cancer mortality after bone-only metastasis will help clarify the clinical course and improve the treatment outcome for patients with breast cancer and bone-only metastasis. Bisphosphonates, as a significant prognostic factor, warrant further investigation.


Subject(s)
Bone Neoplasms/secondary , Breast Neoplasms/pathology , Adult , Antineoplastic Agents/therapeutic use , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Female , Humans , Middle Aged , Multivariate Analysis , Prognosis , Receptors, Estrogen/genetics , Receptors, Progesterone/genetics , Regression Analysis , Retrospective Studies , Survival Analysis
7.
PLoS One ; 8(5): e63510, 2013.
Article in English | MEDLINE | ID: mdl-23717438

ABSTRACT

BACKGROUND: Probability of recurrence in patients with estrogen receptor (ER)-positive breast cancer remains constant for long periods. We compared tumor burden impact on late versus early recurrence in our cohort with long-term follow-up. METHODS: Five hundred and ninety five patients diagnosed with ER-positive breast cancer between 1989 and 2001 were classified into three groups: early recurrence within 5 years, late recurrence after 5 years, and no recurrence. We identified prognostic factors among the groups using logistic regression analysis. RESULTS: At median follow-up of 11.7 years, among 595 ER-positive women, 98 (16.4%) had early recurrence and 58 (9.7%) had late recurrence. On multivariate analysis, higher nodal stage (N0 vs. N2, odds ratio [OR] 3.189; N0 vs. N3, OR 9.948), higher histologic grade (grade 1 vs. grade 2, OR 3.896; grade 1 vs. grade 3, OR 5.945), age >35 years (OR 0.295), and receiving endocrine therapy (OR 0.293) affected early recurrence. Compared to no recurrence, receiving endocrine therapy (OR 0.285) was solely related to decreased risk of late recurrence. Increased risk of early recurrence was noted with the higher nodal stage when early and no recurrences were compared. This phenomenon was not found in late recurrence. In the last comparison between the early and late recurrence, higher nodal stage (N0 vs. N3, OR 16.779) and higher histologic grade (grade 1 vs. grade 3, OR 18.111) repeatedly weighted for early recurrence. CONCLUSIONS: Nodal burden had an attenuated influence on late recurrence, which suggests that, unlike early recurrence, tumor biology might have a more important role than tumor load for late recurrence in ER-positive disease.


Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neoplasm Recurrence, Local/pathology , Receptors, Estrogen/genetics , Adult , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Combined Modality Therapy/methods , Female , Humans , Lymphatic Metastasis/genetics , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Prognosis , Retrospective Studies , Young Adult
8.
Fam Cancer ; 12(1): 75-81, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23131904

ABSTRACT

The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.


Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1 , Genes, BRCA2 , Genetic Testing , Adult , Aged , Breast Neoplasms/epidemiology , Female , Genetic Predisposition to Disease , Humans , Middle Aged , Mutation , Prevalence , Republic of Korea/epidemiology , Young Adult
9.
Yonsei Med J ; 53(3): 537-42, 2012 May.
Article in English | MEDLINE | ID: mdl-22476997

ABSTRACT

PURPOSE: Some recent trials suggest that postoperative adjuvant radiotherapy (RT) may be safely omitted after breast-conserving surgery (BCS) for some patients with ductal carcinoma in situ (DCIS). In this study, we reviewed clinical outcomes of patients with DCIS treated with partial mastectomy (PM) without adjuvant RT. MATERIALS AND METHODS: Medical records of 28 patients (29 breasts) with DCIS who were treated with PM, but without RT, between April 1991 and December 2010 were retrospectively analyzed. Based on established criteria (2.0 cm or less in size and no comedonecrosis), 18 patients were treated without RT after PM. Seven patients (8 breasts) who did not receive RT due to refusal were also included in this study. Three other patients were excluded because data concerning comedonecrosis were not available. RESULTS: For the 25 patients included in this study, the mean age of the 18 patients who met the criteria was 47.9±6.2 years, and 47.6±12.7 years for the 7 patients who did not. The mean sizes of the primary tumors were 0.6±0.4 cm and 0.9±0.3 cm, respectively, in these two groups. Among these 25 patients (26 breasts) treated without RT, we observed no ipsilateral breast tumor recurrence or mortality within a mean follow-up of 84 months. CONCLUSION: Based on this small number of cases, patients with DCIS, who were selected for tumor size less than 2 cm and absence of comedonecrosis, may be treated successfully with BCS; adjuvant RT may be omitted.


Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Intraductal, Noninfiltrating/radiotherapy , Carcinoma, Intraductal, Noninfiltrating/surgery , Mastectomy, Segmental , Radiotherapy, Adjuvant , Adult , Female , Humans , Middle Aged , Retrospective Studies , Treatment Outcome
10.
Breast Cancer Res Treat ; 133(3): 1143-52, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22382806

ABSTRACT

Prevalence and phenotype of BRCA mutation can vary by race. The purpose of this study is to evaluate the prevalence of BRCA1/2 mutations in non-familial breast cancer patients with high risks in Korea. A subset of 758 patients was selected for this study from the KOHBRA nationwide multicenter prospective cohort study. Mutations in BRCA1/2 genes were tested using fluorescent-conformation sensitive gel electrophoresis, denaturing high performance liquid chromatography or direct sequencing. Mutation of BRCA1/2 genes were identified in 65 (8.6%) patients among total 758 patients [BRCA1 mutation: 25 (3.3%), BRCA2 mutation: 40 (5.3%)]. According to risk groups, mutation of BRCA1/2 genes were identified in 53 (8.5%) of 625 early onset patients (age ≤ 40), in 22 (17.7%) of 124 bilateral breast cancer patients, in 3 (50.0%) of 6 breast and ovarian cancer patients, in one (5.9%) of 17 male breast cancer patients, in 5 cases (7.6%) of 66 multiple organ cancer patients. The most common mutation was 509C>A for BRCA1 and 7708C>T for BRCA2. The prevalence of BRCA1/2 mutations by age in early onset patients was significantly different (age <35 vs age ≥35; 10.0 vs 2.9%, p = 0.0007). BRCA1/2 mutations for non-familial Korean breast cancer patients were detected at a high rate, particularly, in patients with early onset of less than 35 years of age, bilateral breast cancer, and breast and ovarian cancer. Individualized genetic counseling should be offered for non-familial breast cancer patients with these risk factors.


Subject(s)
Asian People/genetics , Breast Neoplasms/genetics , Genes, BRCA1 , Genes, BRCA2 , Mutation , Adult , Age of Onset , Breast Neoplasms/epidemiology , Breast Neoplasms, Male/epidemiology , Breast Neoplasms, Male/genetics , Female , Founder Effect , Germ-Line Mutation , Humans , Incidence , Male , Middle Aged , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/genetics , Prevalence , Republic of Korea/epidemiology , Young Adult
11.
J Korean Med Sci ; 26(12): 1569-75, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22147993

ABSTRACT

Bisphosphonates are used routinely to reduce bone-related events in breast cancer patients with bone metastasis. We evaluated the effects of zoledronic acid, a third generation, nitrogen-containing bisphosphonate, to prevent bone metastasis in breast cancer. Zoledronic acid or vehicle alone was administered to nude mice either simultaneously or after intracardiac injection of human breast cancer MDA-MB-231 cells. Nude mice treated with zoledronic acid at early time points showed a lower incidence of bone metastases than did vehicle-treated nude mice, but these differences were not statistically significant. Only 37.5% of mice treated with zoledronic acid at the time of tumor cell inoculation developed bone metastases compared to over 51.8% of mice receiving vehicle alone (P = 0.304). Cell count of apoptosis confirmed by immunohistochemical staining in metastatic bone tissue significantly increased in the zoledronic acid-treated groups compared to non-treated group (1,018.3 vs 282.0; P = 0.046). However, metastatic tumor cells, which invade soft tissue around the bone, did not show extensive apoptosis; there were no differences between the zoledronic acid-treated and control groups. These results suggest that zoledronic acid increases apoptosis of metastatic breast tumor cells in the bone and could therefore reduce metastatic tumor burden. These results support the use of zoledronic acid to reduce the incidence of bone metastasis in breast cancer.


Subject(s)
Bone Neoplasms/secondary , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Diphosphonates/pharmacology , Imidazoles/pharmacology , Animals , Apoptosis/drug effects , Bone Density Conservation Agents/pharmacology , Bone Neoplasms/prevention & control , Bone and Bones/drug effects , Bone and Bones/pathology , Female , Humans , Mice , Mice, Nude , Xenograft Model Antitumor Assays , Zoledronic Acid
12.
Breast Cancer Res Treat ; 130(3): 863-70, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21861101

ABSTRACT

The age distribution of breast cancer patients in Korea, where most are less than 60 years of age and have recently entered menopause, differs from that in the West. The aim of this study was to evaluate bone mineral density (BMD) changes in Korean breast cancer patients treated with an aromatase inhibitor (AI) either alone or in combination with zoledronic acid (ZA). Changes in BMD of the lumbar spine and hip were evaluated in 107 patients receiving AI treatment, of which 59 were treated in combination with ZA. The mean age of the patients was 54.9 years, and the median follow-up period was 38.2 months. With AI treatment alone, BMD loss was significant (all P < 0.0001) in the lumbar spine and hip 12 months (4.18 and 3.95%, respectively), 24 months (6.28 and 5.44%), and 36 months (8.17 and 6.82%) after treatment. In contrast, the combination treatment resulted in increased BMD in the lumbar spine and hip 12 months (2.45 and 0.89%, respectively), 24 months (3.51 and 1.03%), and 36 months (3.85 and 1.80%) after treatment. BMD loss in the lumbar spine was significantly greater in AI alone-treated women who had entered menopause within the past year compared with those who had entered menopause more than 1 year ago, when measured 12 and 24 months after treatment (P = 0.017 and 0.021, respectively). Importantly, ZA effectively inhibited AI-associated bone loss, independent of the postmenopausal interval. Because the proportion of patients in this study who had recently entered menopause was high, bone loss in Korean breast cancer patients treated with AI alone was higher than data reported from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial. In conclusion, we have shown that ZA is very effective in preventing AI-induced bone loss in Korean postmenopausal breast cancer patients.


Subject(s)
Aromatase Inhibitors/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Breast Neoplasms/drug therapy , Diphosphonates/therapeutic use , Imidazoles/therapeutic use , Postmenopause , Adult , Aged , Aromatase Inhibitors/adverse effects , Chemotherapy, Adjuvant , Female , Follow-Up Studies , Humans , Korea , Middle Aged , Osteoporosis/chemically induced , Osteoporosis/prevention & control , Zoledronic Acid
13.
J Korean Med Sci ; 24(6): 1150-7, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19949674

ABSTRACT

This study was designed to assess whether histological and biological factors of breast cancer can predict chemoresponse to specific agents. Adenosine triphosphate-based chemotherapy response assay (ATP-CRA) was employed to retrieve chemoresponse to 5-fluorouracil (5-FU), doxetaxel, doxorubicin, epirubicin, and paclitaxel in 49 patients. Tumors with high histologic and nuclear grade have higher response rate to doxorubicin (P<0.05) and palitaxel (P<0.05). Estrogen receptor (ER)-negative tumors respond well to doxorubicin (P=0.038), and progesterone receptor (PR)-negative tumors to 5-FU (P=0.039), doxetaxel (P=0.038), doxorubicin (P=0.000), epirubicin (P=0.010), and paclitaxel (P=0.003). Among the breast cancer subtypes determined by ER, PR, and HER-2 immunohistochemical stains, the HER-2+/ER- subtype has a higher response rate to doxorubicin (P=0.008). This in vitro result suggests that the combination of histologic and nuclear grade, hormone receptor, and HER-2 status can be a predictive factor of response to specific chemotherapy agents. Further in vivo study should be followed for clinical trials.


Subject(s)
Adenosine Triphosphate/metabolism , Antineoplastic Agents/therapeutic use , Breast Neoplasms , Drug Screening Assays, Antitumor/methods , Receptor, ErbB-2/metabolism , Adult , Aged , Breast Neoplasms/classification , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Doxorubicin/therapeutic use , Epirubicin/therapeutic use , Female , Fluorouracil/therapeutic use , Humans , Middle Aged , Paclitaxel/therapeutic use , Receptor, ErbB-2/genetics , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism
14.
J Biol Chem ; 283(3): 1391-1400, 2008 Jan 18.
Article in English | MEDLINE | ID: mdl-17991742

ABSTRACT

TrkC mediates many aspects of growth and development in the central nervous system. TrkC is expressed in a variety of non-neuronal tissues as well as human cancers. TrkC overexpression may drive tumorigenesis, invasion, and metastatic capability in cancer cells. However, relatively little is known about whether TrkC activity is also essential to maintain the malignant properties in human tumors. TrkC expression leads to the constitutive activation of two major effector pathways, namely the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway mediating cell survival. However, it remains unclear how TrkC activates Ras-Erk1/2 and/or PI3K-Akt cascades. Here we define some aspects of the molecular mechanisms regulating TrkC-dependent Ras-Erk1/2 and PI3K/Akt activation. We show that endogenous TrkC associated with c-Src in human and mouse cancer cells which express TrkC. TrkC-c-Src complexes were also detected in primary human breast cancer tissues. Suppression of c-Src by RNA interference in highly metastatic 4T1 mammary cancer cells, which express endogenous TrkC, resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. Moreover, inhibition of c-Src expression almost completely blocks colony formation of 4T1 cells in soft agar. Furthermore, in c-Src-deficient SYF cells, TrkC failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. Therefore these data indicate that TrkC induces the PI3K-Akt cascade through the activation of c-Src.


Subject(s)
Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins pp60(c-src)/metabolism , Receptor, trkC/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Animals , Cell Line , Cell Line, Tumor , Cell Transformation, Neoplastic/drug effects , Cyclin D1/metabolism , Enzyme Activation/drug effects , Fibroblasts/drug effects , Fibroblasts/enzymology , Humans , Indoles/pharmacology , Insulin Receptor Substrate Proteins , MAP Kinase Kinase 1/metabolism , Mice , Phosphorylation/drug effects , Protein Binding/drug effects , Proto-Oncogene Proteins pp60(c-src)/chemistry , Proto-Oncogene Proteins pp60(c-src)/deficiency , RNA, Small Interfering/metabolism , Sulfonamides/pharmacology , Tumor Stem Cell Assay
15.
Yonsei Med J ; 47(3): 333-42, 2006 Jun 30.
Article in English | MEDLINE | ID: mdl-16807982

ABSTRACT

We investigated the expression of membrane type-1 (MT1)-MMP, MMP2, MMP9 and TIMP2 mRNAs and their roles in ductal carcinoma in situ (DCIS) and T1 and T2 invasive ductal carcinoma of the breast. We further compared these two types of carcinomas for differences in microvessel density, and expression of angiogenic factors and CD44std. MT1-MMP, MMP2, MMP9 and TIMP2 mRNA were expressed in both DCIS and invasive ductal carcinomas. Expression rates of MT1-MMP, MMP2, MMP9 and TIMP2 mRNAs were not statistically different between DCIS and invasive ductal carcinomas, nor did they differ statistically when grouped by tumor size, histologic grade or nuclear grade of invasive ductal carcinoma. Microvessel density and expression of VEGF and TGF-beta1 were not statistically different between DCIS and invasive ductal carcinoma. CD44std expression was significantly increased in DCIS compared to invasive ductal carcinoma (p < 0.05) and it was also significantly increased in lower clinical stage, histologic grade and nuclear grade of invasive ductal carcinoma (p < 0.05). Axillary node metastasis was significantly correlated with MT1-MMP mRNA, VEGF and TGF-beta1 expression (p < 0.05) and MT1-MMP mRNA was positively correlated with VEGF expression and TIMP2 mRNA (p < 0.05). In summary, patterns of MMP mRNA expression in DCIS and invasive ductal carcinoma suggest that the invasive potential of breast carcinoma is already achieved before morphologically overt invasive growth is observed. As MT1-MMP mRNA expression is significantly correlated with axillary nodal metastasis, it may be useful as a prognostic indicator of invasive ductal carcinoma. Considering the positive correlation of MT1-MMP mRNA and TIMP2mRNA expression, our finding supports a role for TIMP2 in tumor growth, as well as the utility of CD44std as a prognostic indicator of breast cancer.


Subject(s)
Breast Neoplasms/physiopathology , Carcinoma in Situ/physiopathology , Carcinoma, Ductal, Breast/physiopathology , Matrix Metalloproteinases/genetics , Breast Neoplasms/genetics , Carcinoma in Situ/genetics , Carcinoma, Ductal, Breast/genetics , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinases, Membrane-Associated , RNA, Messenger/metabolism , Tissue Inhibitor of Metalloproteinase-2/genetics
16.
Yonsei Med J ; 47(2): 259-63, 2006 Apr 30.
Article in English | MEDLINE | ID: mdl-16642558

ABSTRACT

Metaplastic breast carcinoma is very rare, and metaplastic carcinoma with chondroid differentiation is even rarer. Here, we report a case of metaplastic carcinoma with extensive chondroid differentiation mimicking chondrosarcoma that was challenging to diagnose. The tumor was characterized by an abundant chondromyxoid matrix. The definitive area of classic invasive ductal carcinoma was minimal. The peripheral portion of the tumor showed increased cellularity with pleomorphism and definitive invasive growth. Tumor cells in the chondrosarcomatous areas were diffusely immunoreactive for S-100 protein, patchy positive for cytokeratin, but negative for epithelial membrane antigen (EMA). Tumor cells in carcinomatous areas were diffusely positive for cytokeratin, S-100 protein, and patchy positive for EMA. In both areas, tumor cells were negative for smooth muscle actin (SMA) and CD34, while oncoprotein p53 was overexpressed. When pathologists encounter breast tumors with chondroid differentiation, careful sampling and immunohistochemistry for cytokeratin and SMA are most helpful to differentiate metaplastic carcinoma from malignant phyllodes tumor and malignant adenomyoepithelioma.


Subject(s)
Breast Neoplasms/pathology , Carcinoma/complications , Actins/metabolism , Antigens, CD34/biosynthesis , Breast Neoplasms/complications , Breast Neoplasms/metabolism , Carcinoma/metabolism , Carcinoma/pathology , Cell Differentiation , Female , Humans , Immunohistochemistry , Keratins/metabolism , Metaplasia , Middle Aged , Mucin-1/metabolism , Muscle, Smooth/pathology , Neoplasm Metastasis , S100 Proteins/chemistry
17.
Breast Cancer Res Treat ; 86(2): 107-15, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15319563

ABSTRACT

Metastasis is the leading cause of death in breast cancer patients and an appropriate detection of metastasis can provide better prognosis and quality treatments. Microwaves can reveal the unique electromagnetic properties of materials, and this study aims to unleash the electromagnetic properties of breast cancer cells, especially, metastasized cancer cells in the lymph nodes, using broad-band microwaves in attempts to detect metastases. To distinguish the cancer-specific patterns of cancer tissues, three primary microwave parameters were assessed, i.e., permittivity in mid-band frequency (3-5 GHz), conductivity in high-band frequencies (25-30 GHz) and slope changes of permittivity at high-band frequencies (15-30 GHz). An additional parameter, Cancer Metastasis Index (CMI), was developed to effectively represent all parameters. Broadband microwave scanning can reveal cancer specific electromagnetic behaviors in all three parameters, and these were reliably reflected by CMI. CMI effectively magnified the difference of the electromagnetic properties between normal nodal tissues and cancer tissues. immunohistochemistries were performed to verify the origin of electromagnetic changes represented by CMI values.


Subject(s)
Breast Neoplasms/pathology , Carcinoma/pathology , Lymphatic Metastasis/diagnosis , Microwaves , Neoplasm Metastasis/physiopathology , Sentinel Lymph Node Biopsy/methods , Electrophysiology , Female , Humans , Immunohistochemistry , Lymphatic Metastasis/pathology , Prognosis , Tumor Cells, Cultured
18.
Yonsei Med J ; 44(5): 828-35, 2003 Oct 30.
Article in English | MEDLINE | ID: mdl-14584099

ABSTRACT

To identify the effect of post-operative irradiation to the thyroid gland in patients with breast carcinoma. Seventy seven patients with partial or total mastectomized breast carcinoma who received routine irradiation therapy (Hockey stick method: supraclavicular, internal mammary lymph nodes, and chest wall irradiation with 5,040 rads, divided into 30 treatments) were reviewed in terms of their ipsilateral thyroid gland response. All patients had the bilateral thyroid sizes measured annually by ultrasonography before and after radiation therapy. In the one-year follow-up group (n=77), 32 patients (41.5%) demonstrated decreased ipsilateral thyroid gland size after Hockey Stick irradiation therapy (p=0.428), in the two-year follow-up group (n=37), 26 patients (70.3%) demonstrated decreased gland size after Hockey Stick irradiation (p=0.001), and in the three-year follow-up group (n=21), 15 patients (71.4%) showed a decreased thyroid gland size (p=0.005). Most the patients with breast carcinoma (32/77 at the one-year follow-up, 26/37 at the two-year follow-up, and 15/21 at the three-year follow-up) after post-operative Hockey Stick irradiation therapy showed reduced ipsilateral thyroid gland size. Routine en face treatment of the supraclavicular lymph nodes, using the Hockey Stick method, should be reconsidered.


Subject(s)
Breast Neoplasms/radiotherapy , Lymph Nodes/radiation effects , Thyroid Gland/radiation effects , Female , Follow-Up Studies , Humans , Radiotherapy/adverse effects , Thyroid Gland/pathology
SELECTION OF CITATIONS
SEARCH DETAIL
...